Pre-Operative Interictal Discharge Patterns and Magnetic Resonance Imaging Findings Affect Prognosis of Temporal Lobe Epilepsy Surgery.
This study investigated whether pre-operative interictal discharge patterns detected by electroencephalogram (EEG) and magnetic resonance imaging (MRI) findings affect the surgical prognosis in temporal lobe epilepsy (TLE) patients. A retrospective analysis of 115 cases of patients with refractory TLE was carried out from October 2010 to 2014 based on the classification of pre-operative interictal discharge patterns in EEG and MRI findings. The patients were followed up for 4 years after surgery. The ILAE method was used to assess differences in seizure-free rate among different types of interictal discharge pattern as well as in MRI findings. A total of 115 cases were classified according to interictal discharge patterns in EEG, including normal cases, unilateral anterior discharge, unilateral multi-region discharge, and bilateral discharge. MRI findings were classified into negative results and positive results. Unilateral anterior and bilateral discharges showed statistically significant differences in post-operative seizure-free rates (p< 0.001). MRI-positive cases showed good overall post-operative outcome, irrespective of interictal discharge pattern in the EEG, whereas MRI-negative cases showed good overall prognosis if the interictal discharge pattern in EEG occurred in the unilateral anterior region. If the pre-operative interictal discharge pattern in EEG is confined to the unilateral anterior region, prognosis is good. If there are abnormalities in MRI findings, post-operative prognosis is good, regardless of pre-operative interictal discharge patterns in EEG. Surgical intervention is highly recommended for TLE patients with normal MRI findings and interictal discharge confined to the unilateral anterior region.


Comparative genomics analysis of Streptococcus isolates from the human small intestine reveals their adaptation to a highly dynamic ecosystem.
The human small-intestinal microbiota is characterised by relatively large and dynamic Streptococcus populations. In this study, genome sequences of small-intestinal streptococci from S. mitis, S. bovis, and S. salivarius species-groups were determined and compared with those from 58 Streptococcus strains in public databases. The Streptococcus pangenome consists of 12,403 orthologous groups of which 574 are shared among all sequenced streptococci and are defined as the Streptococcus core genome. Genome mining of the small-intestinal streptococci focused on functions playing an important role in the interaction of these streptococci in the small-intestinal ecosystem, including natural competence and nutrient-transport and metabolism. Analysis of the small-intestinal Streptococcus genomes predicts a high capacity to synthesize amino acids and various vitamins as well as substantial divergence in their carbohydrate transport and metabolic capacities, which is in agreement with observed physiological differences between these Streptococcus strains. Gene-specific PCR-strategies enabled evaluation of conservation of Streptococcus populations in intestinal samples from different human individuals, revealing that the S. salivarius strains were frequently detected in the small-intestine microbiota, supporting the representative value of the genomes provided in this study. Finally, the Streptococcus genomes allow prediction of the effect of dietary substances on Streptococcus population dynamics in the human small-intestine.


Effects of sesame oil in the model of adjuvant arthritis.
The goal of this study was to evaluate the effect of sesame oil on functional damage induced by adjuvant arthritis (AA) and on changes of selected biochemical parameters reflecting oxidative tissue injury. Mycobacterium butyricum in incomplete Freund's adjuvans was intradermally administered to Lewis male rats. Hind paw edema and endothelium-dependent relaxation of the aorta were determined on day 28. Further, plasmatic levels of TBARS, gamma-glutamyltransferase (GGT) activity in the joint and spleen tissues, level of protein carbonyls and total antioxidant capacity (TAC) in plasma, as well as activity of the lysosomal enzyme N-acetyl-glucosaminidase (NAGA) in serum were assessed. The effect of sesame oil (SO, 1ml/kg, daily oral administration) was evaluated on day 28. The beneficial effect of sesame oil on markers of oxidative stress accompanying AA was demonstrated by decrease of plasma TBARS and decrease of GGT activity in the joint and spleen tissues. Level of protein carbonyls, TAC in plasma and activity of NAGA in serum and in the kidney were improved, yet not significantly. In the hind paw edema the maximal increase was found on day 28 of AA, and in the same time we observed a significant decrease of aortic endothelium-dependent relaxation. Administration of SO resulted in mild, non-significant decrease of hind paw swelling and in significantly increased acetylcholine-evoked relaxation. We conclude that SO has beneficial effects on oxidative stress induced biochemical changes occurring in AA, moreover it improves endothelium-dependent relaxation of the aorta and tends to decrease hind paw edema.


Gold nanoparticle fluorescent molecular beacon for low-resolution DQ2 gene HLA typing.
Coeliac disease is an inflammation of the small intestine triggered by gluten ingestion. We present a fluorescent genosensor, exploiting molecular-beacon-functionalized gold nanoparticles, for the identification of human leukocyte antigen (HLA) DQ2 gene, a key genetic factor in coeliac disease. Optimization of sensor performance was achieved by tuning the composition of the oligonucleotide monolayer immobilized on the gold nanoparticle and the molecular beacon design. Co-immobilization of the molecular beacon with a spacing oligonucleotide (thiolated ten-thymine oligonucleotide) in the presence of ten-adenine oligonucleotides resulted in a significant increase of the sensor response owing to improved spacing of the molecular beacons and extension of the distance from the nanoparticle surface, which renders them more available for recognition. Further increase in the response (approximately 40%) was shown to be achievable when the recognition sequence of the molecular beacon was incorporated in the stem. Improvement of the specificity of the molecular beacons was also achieved by the incorporation within their recognition sequence of a one-base mismatch. Finally, gold nanoparticles functionalized with two molecular beacons targeting the DQA1*05* and DQB1*02* alleles allowed the low-resolution typing of the DQ2 gene at the nanomolar level.


Translation of an uncapped mRNA involves scanning.
tat, an essential gene of human immunodeficiency virus, when placed under the control of the RNA polymerase III promoter from the adenovirus VA RNA1 gene, is transcribed into an uncapped and nonpolyadenylated mRNA. This VA-Tat RNA is translated to produce functional Tat protein in transfected mammalian cells (Gunnery, S., and Mathews, M. B. (1995) Mol. Cell. Biol. 15, 3597-3607). The presence of an upstream open reading frame (ORF) in VA-Tat RNA is inhibitory to the translation of the Tat ORF, suggesting that the RNA is scanned during translation even though it is uncapped. Because the effect of the upstream ORF is relatively small (about 2-fold), we sought more definitive evidence of scanning by introducing secondary structures of varying stabilities into the 5'-untranslated region of VA-Tat RNA. The results of transfection experiments showed that highly stable secondary structure was inhibitory to Tat synthesis, whereas structures of lower stability were not inhibitory, confirming that uncapped mRNA is subject to scanning. Furthermore, translation of the downstream ORF was reduced but not eliminated by mutations that caused the upstream ORF to overlap the Tat ORF. Extending the overlap of the two ORFs further decreased the translation of the downstream ORF. This observation implies that ribosomes reinitiate after termination, possibly after migrating in a 3' to 5' direction through the overlap region of the mRNA. Similar results were obtained with a capped polymerase II transcript, indicating that the translation of polymerase II and polymerase III transcripts occurs through similar mechanisms.


A pharmacodynamic study of the optimal P2Y12 inhibitor regimen for East Asian patients with acute coronary syndrome.
Newer P2Y12 inhibitors, such as prasugrel and ticagrelor, have greater antiplatelet efficacy but may increase the risk of bleeding. In this study, we compared the pharmacodynamic efficacy of prasugrel and ticagrelor in East Asian patients with acute coronary syndrome (ACS). We selected 83 ACS patients undergoing percutaneous coronary intervention who were discharged with 90 mg ticagrelor twice daily (n = 24), 10 mg prasugrel daily (n = 39) or 5 mg prasugrel daily (n = 20). After 2 to 4 weeks, on-treatment platelet reactivity (OPR) was assessed in terms of P2Y12 reaction units (PRUs) using the VerifyNow P2Y12 assay (Accumetrics). We compared East Asian (85 < PRU ≤ 275) and Caucasian (85 < PRU ≤ 208) criteria for assessing the therapeutic window of OPR. OPR was lowest in the ticagrelor group, followed by the 10 mg prasugrel and 5 mg prasugrel groups (49.1 ± 29.9 vs. 83.7 ± 57.1 vs. 168.5 ± 60.8, respectively; p < 0.001). The 5 mg prasugrel group had the highest proportion of patients with OPR values within the therapeutic window, followed by the 10 mg prasugrel and ticagrelor groups (90.0% vs. 46.2% vs. 12.5%, respectively; p < 0.001 for East Asian criteria; 60.0% vs. 43.6% vs. 12.5%, respectively; p < 0.001 for Caucasian criteria). Short-term administration of 5 mg prasugrel facilitated maintenance within the therapeutic window of OPR compared with the 10 mg prasugrel and ticagrelor groups. Thus, 5 mg prasugrel daily may be the optimal antiplatelet regimen for stabilized East Asian ACS patients.


Disorganization Theory, Neighborhood Social Capital, and Ethnic Inequalities in Intimate Partner Violence between Arab and Jewish Women Citizens of Israel.
We draw on social disorganization (SD) theory and social capital to examine the impact of neighborhood environment on the ethnic gap in intimate partner violence (IPV) between Arab and Jewish women in Israel. We linked census data on neighborhood socioeconomic status (SES) to national data we gathered in 2014-2015 on 1401 women (436 Arab, 965 Jewish) age 16-48. Women were interviewed while visiting 65 maternal and child health clinics throughout Israel. We used General Estimated Equation (GEE) multivariate logistic regression models to adjust for clinic cluster effects and estimated the contribution of neighborhood collective efficacy, problems, relative socioeconomic status (SES), bridging and linking social capital, and social support to explaining ethnic inequalities in IPV, while adjusting for women's socioeconomic and socio-demographic characteristics. We found that any IPV is higher among Arab compared to Jewish women (odds ratio (OR) and 95% confidence intervals (CI) = 4.19 (2.72,6.42)). Collective efficacy and social group membership (bridging social capital) had no effect on the ethnic inequality in any IPV and types of IPV. Women's active participation in social groups (linking social capital), higher social support, and living in neighborhoods with relative SES similar to the ethnic group average) had a protective effect from any IPV and physical IPV. Neighborhood problems were associated with increased any IPV and physical IPV. In the final model, the ethnic gap in IPV was reduced but not eliminated (OR (95%CI) = 3.28 (2.01, 5.35). Collective efficacy did not explain the ethnic gap in IPV, while women's active participation (linking social capital) had a protective effect from IPV. Given the protective nature of women's activism in this population, future research should investigate how this might be incorporated into solutions to IPV. In addition, reducing neighborhood problems, improving neighborhood SES, and increasing social support might help reduce IPV among Arab women, thus decreasing the ethnic gap in IPV.


Attentional bias retraining in cigarette smokers attempting smoking cessation (ARTS): study protocol for a double blind randomised controlled trial.
Smokers attend preferentially to cigarettes and other smoking-related cues in the environment, in what is known as an attentional bias. There is evidence that attentional bias may contribute to craving and failure to stop smoking. Attentional retraining procedures have been used in laboratory studies to train smokers to reduce attentional bias, although these procedures have not been applied in smoking cessation programmes. This trial will examine the efficacy of multiple sessions of attentional retraining on attentional bias, craving, and abstinence in smokers attempting cessation. This is a double-blind randomised controlled trial. Adult smokers attending a 7-session weekly stop smoking clinic will be randomised to either a modified visual probe task with attentional retraining or placebo training. Training will start 1 week prior to quit day and be given weekly for 5 sessions. Both groups will receive 21 mg transdermal nicotine patches for 8-12 weeks and withdrawal-orientated behavioural support for 7 sessions. Primary outcome measures are the change in attentional bias reaction time and urge to smoke on the Mood and Physical Symptoms Scale at 4 weeks post-quit. Secondary outcome measures include differences in withdrawal, time to first lapse and prolonged abstinence at 4 weeks post-quit, which will be biochemically validated at each clinic visit. Follow-up will take place at 8 weeks, 3 months and 6 months post-quit. This is the first randomised controlled trial of attentional retraining in smokers attempting cessation. This trial could provide proof of principle for a treatment aimed at a fundamental cause of addiction. Current Controlled Trials: ISRCTN54375405.


Satellite-based forest monitoring: spatial and temporal forecast of growing index and short-wave infrared band.
For detecting anomalies or interventions in the field of forest monitoring we propose an approach based on the spatial and temporal forecast of satellite time series data. For each pixel of the satellite image three different types of forecasts are provided, namely spatial, temporal and combined spatio-temporal forecast. Spatial forecast means that a clustering algorithm is used to group the time series data based on the features normalised difference vegetation index (NDVI) and the short-wave infrared band (SWIR). For estimation of the typical temporal trajectory of the NDVI and SWIR during the vegetation period of each spatial cluster, we apply several methods of functional data analysis including functional principal component analysis, and a novel form of random regression forests with online learning (streaming) capability. The temporal forecast is carried out by means of functional time series analysis and an autoregressive integrated moving average model. The combination of the temporal forecasts, which is based on the past of the considered pixel, and spatial forecasts, which is based on highly correlated pixels within one cluster and their past, is performed by functional data analysis, and a variant of random regression forests adapted to online learning capabilities. For evaluation of the methods, the approaches are applied to a study area in Germany for monitoring forest damages caused by wind-storm, and to a study area in Spain for monitoring forest fires.


Adherence and viability of primary human keratinocytes and primary human dermal fibroblasts on acrylonitrile-based copolymers with different concentrations of positively charged functional groups.
As shown in several studies, various properties of biomaterials such as stiffness, surface roughness, chemical composition or the amount of functional groups at the surface can influence adhesion, viability, proliferation and functionalities of cells. The aim of this work was to explore whether a cell-selective effect could be achieved for acrylonitrile-based copolymers containing different contents of positively charged functional groups, which were introduced by incorporation of methacrylic acid-2-aminoethylester hydrochloride (AEMA) units. The p(AN-co-AEMA) copolymers were synthesized by suspension polymerization in water and processed into disk shaped test specimen via a sintering process to ensure the absence of organic solvents in the copolymers. Copolymers with an AEMA content of 1.4, 1.6, and 4.4 mol-% were investigated according to their cell-selective capacity, which should support the adhesion, viability and proliferation of keratinocytes, while the adherence of fibroblasts should rather be disabled. The test samples were seeded with primary human keratinocytes and primary human dermal fibroblasts in mono- as well as in co-cultures. Tissue culture plate polystyrene (TCP) was used to control the physiologic growth of the cells. Density and viability of attached and non-adherent cells were analyzed by live/dead staining, lactate dehydrogenase (LDH) assay and flow cytometry with DAPI staining. For the assured discrimination of adherent cell types in coculture a keratin/vimentin-staining was performed. On copolymers with 4.4 mol-% AEMA adherent keratinocytes in monoculture and cocultured keratinocytes and fibroblasts showed a higher viability, a lower impairment of cell membranes and higher densities of viable cells compared to both other copolymers. For adherent fibroblasts these parameters did not differ between the copolymers and an increasing ratio of keratinocytes to fibroblasts in cocultures were found with increasing AEMA content. The results showed that keratinocytes and fibroblasts can be influenced by copolymers with different contents of positively charged functional groups. Since the tendency of a better adherence and viability of keratinocytes with increasing amounts of positively charged functional groups was shown, the potential enhancement by further increase of the amount of positively charged functional groups shall be tested in a future study.


Acute compartment syndrome of the thigh in a rugby player.
In the absence of obvious trauma, diagnosis of acute compartment syndrome (ACS) of the thigh can easily be delayed, as disproportional pain is not always present. We present a case of ACS of the anterior right thigh compartment in a healthy, semiprofessional rugby player with normal coagulation, who sustained a seemingly innocuous blow during a rugby match. Following early surgical fasciotomy, he returned to his preinjury playing standards within 12 months. Our literature review suggests that high muscle mass, young, athletic males participating in a contact sport are mostly at risk of developing ACS of the thigh.


Development of the Italian Version of the Pain Vigilance and Awareness Questionnaire in Subjects with Chronic Low Back Pain: Cross-cultural Adaptation, Confirmatory Factor Analysis, Reliability and Validity.
Growing attention is being given to cognitive-behavioural measures to improve interventions for spinal disorders. The Pain Vigilance and Awareness Questionnaire (PVAQ) has never been validated in Italian subjects with chronic low back pain (LBP). The purpose of this study is translating, culturally adapting and validating the Italian version of PVAQ (PVAQ-I). A cross-sectional evaluation of the psychometric properties of the PVAQ-I on patients with chronic LBP was conducted. The questionnaire was culturally adapted in accordance with international standards. The psychometric testing included confirmatory factor analysis, reliability by internal consistency (Cronbach's alpha) and test-retest reliability (intra-class correlation coefficient, ICC); construct validity by comparing the PVAQ-I with the Pain Catastrophising Scale (PCS), the Tampa Scale of Kinesiophobia (TSK), the Hospital Anxiety and Depression Score (HADS), the Chronic Pain Acceptance Questionnaire (CPAQ), a Numerical Rating Scale of pain intensity (NRS) and the Oswestry Disability Questionnaire (ODI); and sensitivity to change by calculating the smallest detectable change. The PVAQ-I was administered to 131 subjects with chronic LBP (77 females, mean age of 48 ± 16 years, median symptoms duration of 12 months). Factor analysis confirmed a two-factor (passive awareness and active vigilance), 13-item solution, which led to an acceptable data-model fit. Internal consistency (α = 0.91) and test-retest reliability (ICC = 0.92) were good. As a priori hypothesized, construct validity showed moderate correlations between the PVAQ-I and PCS (r = 0.60), TSK (r = 0.44) and HADS-Anxiety (r = 0.53) and low correlations with HADS-Depression (r = 0.28), NRS (r = 0.28), ODI (r = 0.23) and CPAQ (r = -0.12). The smallest detectable change was 9. The PVAQ was successfully translated into Italian and proved to have satisfactory psychometric properties. Its use is recommended for clinical and research purposes.


An overview of the use of artificial neural networks in lung cancer research.
The artificial neural networks (ANNs) are statistical models where the mathematical structure reproduces the biological organisation of neural cells simulating the learning dynamics of the brain. Although definitions of the term ANN could vary, the term usually refers to a neural network used for non-linear statistical data modelling. The neural models applied today in various fields of medicine, such as oncology, do not aim to be biologically realistic in detail but just efficient models for nonlinear regression or classification. ANN inference has applications in tasks that require attention focusing. ANNs also have a niche to carve in clinical decision support, but their success depends crucially on better integration with clinical protocols, together with an awareness of the need to combine different paradigms to produce the simplest and most transparent overall reasoning structure, and the will to evaluate this in a real clinical environment. We have performed an assessment of the evidence for improvements in the use of ANN in lung cancer research. Our analysis showed that often the use of ANN in the medical literature had not been performed in an accurate manner. A strict cooperation between physician and biostatisticians could be helpful in determine and resolve these errors.


Human kidney pericytes produce renin.
Pericytes, perivascular cells embedded in the microvascular wall, are crucial for vascular homeostasis. These cells also play diverse roles in tissue development and regeneration as multi-lineage progenitors, immunomodulatory cells and as sources of trophic factors. Here, we establish that pericytes are renin producing cells in the human kidney. Renin was localized by immunohistochemistry in CD146 and NG2 expressing pericytes, surrounding juxtaglomerular and afferent arterioles. Similar to pericytes from other organs, CD146+CD34-CD45-CD56- renal fetal pericytes, sorted by flow cytometry, exhibited tri-lineage mesodermal differentiation potential in vitro. Additionally, renin expression was triggered in cultured kidney pericytes by cyclic AMP as confirmed by immuno-electron microscopy, and secretion of enzymatically functional renin, capable of generating angiotensin I. Pericytes derived from second trimester human placenta also expressed renin in an inducible fashion although the renin activity was much lower than in renal pericytes. Thus, our results confirm and extend the recently discovered developmental plasticity of microvascular pericytes, and may open new perspectives to the therapeutic regulation of the renin-angiotensin system.


Mobile phone messaging reminders for attendance at healthcare appointments.
Missed appointments are a major cause of inefficiency in healthcare delivery, with substantial monetary costs for the health system, leading to delays in diagnosis and appropriate treatment. Patients' forgetfulness is one of the main reasons for missed appointments, and reminders may help alleviate this problem. Modes of communicating reminders for appointments to patients include face-to-face communication, postal messages, calls to landlines or mobile phones, and mobile phone messaging. Mobile phone messaging applications such as Short Message Service (SMS) and Multimedia Message Service (MMS) could provide an important, inexpensive delivery medium for reminders for healthcare appointments. To assess the effects of mobile phone messaging reminders for attendance at healthcare appointments. Secondary objectives include assessment of patients' and healthcare providers' evaluation of the intervention; costs; and possible risks and harms associated with the intervention. We searched the Cochrane Central Register of Controlled Trials (CENTRAL,The Cochrane Library 2009, Issue 2), MEDLINE (OvidSP) (January 1993 to June 2009), EMBASE (OvidSP) (January 1993 to June 2009), PsycINFO (OvidSP) (January 1993 to June 2009), CINAHL (EbscoHOST) (January 1993 to June 2009), LILACS (January 1993 to June 2009) and African Health Anthology (January 1993 to June 2009). We also reviewed grey literature (including trial registers) and reference lists of articles. We included randomised controlled trials (RCTs), quasi-randomised controlled trials (QRCTs), controlled before-after (CBA) studies, or interrupted time series (ITS) studies with at least three time points before and after the intervention. We included studies assessing mobile phone messaging as reminders for healthcare appointments. We only included studies in which it was possible to assess effects of mobile phone messaging independent of other technologies or interventions. Two review authors independently assessed all studies against the inclusion criteria, with any disagreements resolved by a third review author. Study design features, characteristics of target populations, interventions and controls, and results data were extracted by two review authors and confirmed by a third author. Primary outcomes of interest were rate of attendance at healthcare appointments. We also considered health outcomes as a result of the intervention, patients' and providers' evaluation of the intervention, perceptions of safety, costs, and potential harms or adverse effects. As the intervention characteristics and outcome measures were similar across included studies, we conducted a meta-analysis to estimate an overall effect size. We included four randomised controlled trials involving 3547 participants. Three studies with moderate quality evidence showed that mobile text message reminders improved the rate of attendance at healthcare appointments compared to no reminders (risk ratio (RR) 1.10 (95% confidence interval (CI) 1.03 to 1.17)). One low quality study reported that mobile text message reminders with postal reminders, compared to postal reminders, improved rate of attendance at healthcare appointments (RR 1.10 (95% CI 1.02 to 1.19)). However, two studies with moderate quality of evidence showed that mobile phone text message reminders and phone call reminders had a similar impact on healthcare attendance (RR 0.99 (95% CI 0.95 to 1.03). The costs per attendance of mobile phone text message reminders were shown to be lower compared to phone call reminders. None of the included studies reported outcomes related to harms or adverse effects of the intervention, nor health outcomes or user perception of safety related to the intervention. There is moderate quality evidence that mobile phone text message reminders are more effective than no reminders, and low quality evidence that text message reminders with postal reminders are more effective than postal reminders alone. Further, according to the moderate quality evidence we found, mobile phone text message reminders are as effective as phone call reminders. Overall, there is limited evidence on the effects of mobile phone text message reminders for appointment attendance, and further high-quality research is required to draw more robust conclusions.


Hypoglycaemia and hypocalcaemia as determinants of admission birth weight criteria for term stable low risk macrosomic neonates.
Large for gestational age (LGA) accounts for about 6.3% of admissions in kenyatta national hospital, newborn unit. As a policy all IGA's, defined by birth weight of 4000 g and above are admitted for 24 hours to monitor blood glucose levels. The rational for this policy is questionable and contributes to unnecessary burden on resources needed for new born care. To study birth weight related incidence of hypoglycemia and hypocalcaemia in stable low risk lgas in knh and use it to establish a new admission weight based criteria. prospective cohort study done in new born-unit, post natal and labour wards of knh. Term lga neonates (birth weight = 4000 g) were recruited as subjects and controlled against term appropriate weight (aga) neonates. the incidence of hypoglycemia and hypocalcaemia in lgas was 21% and 9% respectively. Hypoglycemia was rarely encountered after 12 hours of life in lgas. Hypoglycemia and hypocalcaemia showed a direct upward relationship with weight beyond 4250 g. No significant difference in incidence of hypoglycemia and hypocalcaemia between controls and 4000-4249 g category to justify their routine admission to newborn unit. the study identified 4275 g as new admission birth weight criteria for stable term low risk IGA's admission.


Therapeutic target and molecular mechanism of vitamin C-treated pneumonia: a systematic study of network pharmacology.
Vitamin C (VC), a well-reported antioxidant, is found with beneficial actions of preventing and treating pneumonia. However, the detailed pharmacological target and mechanism of VC-treated pneumonia remain unclear. Thus, the present bioinformatics approach using systematic network pharmacology aimed to reveal primary predictive targets, cellular processes, and molecular pathways of VC-treated pneumonia. As shown in bioinformatics assays, the data included 90 primary presumptive targets of VC-treated pneumonia, and 5 other core targets of VC-treated pneumonia were identified as mitogen activated protein kinase 1 (MAPK1), c-c chemokine receptor type 5 (CCR5), mitogen activated protein kinase 3 (MAPK3), angiotensin II type 2 (AT-2) receptor (AGTR2), and signal transducer and activator of transcription 3 (STAT3). In addition, all biological processes (including top 20) and signaling pathways (including top 20) of VC-treated pneumonia were identified and illustrated through bioinformatics analyses. In conclusion, VC-achieved anti-pneumonia effects are mechanically implicated with the suppression of inflammation and enhancement of immunoregulation associated with functional processes and signaling pathways. More interestingly, the identified VC targets may act as biomarkers for the diagnosis and treatment of pneumonia.


Patients' experience post-lumbar fusion regarding back problems, recovery and expectations in terms of the International Classification of Functioning, Disability and Health.
To describe within the context of the International Classification of Functioning, Disability and Health (ICF), patient's experiences post-lumber fusion regarding back problems, recovery and expectations of rehabilitation and to contrast with the content of outcome measures and the ICF low back pain (LBP) core sets. The study has a cross-sectional and retrospective design and involves 20 lumbar fusion patients. Using the ICF, qualitative content analysis of semi-structured interviews 3-6 months post-surgery was performed. This was compared with the ICF related content of the Oswestry Disability Index (ODI), Medical Outcome Study Short Form 36 (SF-36), European Quality of Life Questionnaire (EQ5D) and the ICF LBP core sets. Patient's experiences were most frequently linked to psychological, sensory, neuromusculoskeletal and movement related body function chapters of the ICF. The most frequently linked categories of activity and participation were mobility, domestic activities, family relationships, work, recreation and leisure. Environmental factors frequently linked were the use of analgesics, walking aids, family support, social security systems, health care systems and labour market employment services. This study highlights important ICF related aspects of patient's experiences post-lumber fusion. The use of the comprehensive ICF core sets is recommended in conjunction with ODI, SF-36 and the EQ5D for a broader analysis of patient outcomes post-lumbar fusion.


The assessment of the effect of different intraabdominal pressures used for laparoscopic cholecystectomy surgery on optic nerve sheath diameter: a prospective observational cohort study
During laparoscopic cholecystectomy operations, increases in intraabdominal, intrathoracic, and intracranial pressures (ICP) can be seen after pneumoperitoneum created for surgical imaging. Orbital ultrasonography (USG), which has been developed in recent years, is a method that can evaluate the ICP by measuring the optic nerve sheath diameter (ONSD) from the eyeball. In our study, we aimed to evaluate whether different intraabdominal pressure values created during laparoscopic cholecystectomy operations correlate with ICP by measuring ONSD. The study included a total of 90 patients with American Society of Anesthesiologists (ASA) physical status classification I (ASA I) and II (ASA II) and ages from 18 to 65 years with laparoscopic cholecystectomy planned. After the patients were intubated, at the 5th min, bilateral ONSD measurements were performed. The same measurements were performed at the 15th and 30th min after CO2 insufflation and additionally 10 min after CO2 was released at the end of the operation. During intrabdominal CO2 insufflation, patients with 10 mmHg pressure applied comprised Group 1, patients with 12 mmHg pressure applied comprised Group 2, and patients with 14 mmHg pressure applied comprised Group 3. The study was completed with 89 patients, 51 female and 38 males. One patient was excluded from the study due to erroneous values. The variations in ONSD measured in the right-left eye before pneumoperitoneum and at the 15th and 30th min after abdominal CO2 insufflation were observed to be statistically significant (p < 0.01). In all three groups, the right and left eye ONSD values were not identified to be statistically significantly different (p > 0.01). A significant increase was observed in ONSD values in direct proportion to the increase in intraabdominal pressure in patients undergoing laparoscopic cholecystectomy surgery. USG-guided ONSD measurements appear be a guide to ensure optimization of intraabdominal pressures and safe anesthesia administration for patients, especially those at risk of ICP increase, during laparoscopic surgery.


Chemical Contamination Transfer in the Management of War Casualties.
The use of chemical weapons agents (CWAs) was suspected in recent conflicts, during international conflicts, terrorist attacks, or civil wars. Little is known about the prevention needed for caregivers exposed to the risk of contamination transfer. We present a case of chemical contamination of health servicemembers during the management of casualties.


Toward the two-step microdynamic phase transition mechanism of an oligo(ethylene glycol)methacrylate-based copolymer with a LCST-type poly(ionic liquid) block.
A new LCST-type thermoresponsive polyelectrolyte P[P4,4,4,4][SS], poly(tetrabutyl phosphonium styrene sulfonate), was introduced to PMEO2MA (poly(2-(2-methoxyethoxy)ethyl methacrylate)) via RAFT polymerization, in order to explore the transition behavior of the block copolymer PMEO2MA-b-P[P4,4,4,4][SS] with two distinct LCST-type segments. A relatively sharp LCST-type phase transition with only one transition point is observed in the turbidity curves, while the whole phase transition is completely different from the micro perspective. The phase transition temperature range is relatively broad, according to the unsynchronized changes of different protons of the two blocks in the temperature-variable 1H NMR analysis. From PCMW analysis, it is found that there exists an obvious two-step phase transition behavior, especially in the region of the C-H groups. Accordingly, we divided the whole transition process into two subregions: 20-40 °C and 40-55 °C in 2Dcos analysis. At the first stage of 20-40 °C, the CH3 groups mainly belonging to the backbones of PMEO2MA blocks have the earliest response to the heating and drive the first step of the dehydration process of PMEO2MA-b-P[P4,4,4,4][SS], resulting in the formation of an intermediate micelle state composed of the collapsed PMEO2MA core and hydrophilic P[P4,4,4,4][SS] corona. In particular, the conformational changes and the more compact structures due to the interaction between the C[double bond, length as m-dash]O groups and P[P4,4,4,4][SS] segments (ν(C[double bond, length as m-dash]OD2O-PILs)) were observed using IR analysis. With the continual increase of the temperature, when the second temperature range of 40-55 °C is reached, the P[P4,4,4,4][SS] segments start to collapse and expel the water molecules, driven by the anions of the poly(ionic liquid)s, with the phosphonium cations being distributed over the relatively hydrophilic outside.


PAAR-repeat proteins sharpen and diversify the type VI secretion system spike.
The bacterial type VI secretion system (T6SS) is a large multicomponent, dynamic macromolecular machine that has an important role in the ecology of many Gram-negative bacteria. T6SS is responsible for translocation of a wide range of toxic effector molecules, allowing predatory cells to kill both prokaryotic as well as eukaryotic prey cells. The T6SS organelle is functionally analogous to contractile tails of bacteriophages and is thought to attack cells by initially penetrating them with a trimeric protein complex called the VgrG spike. Neither the exact protein composition of the T6SS organelle nor the mechanisms of effector selection and delivery are known. Here we report that proteins from the PAAR (proline-alanine-alanine-arginine) repeat superfamily form a sharp conical extension on the VgrG spike, which is further involved in attaching effector domains to the spike. The crystal structures of two PAAR-repeat proteins bound to VgrG-like partners show that these proteins sharpen the tip of the T6SS spike complex. We demonstrate that PAAR proteins are essential for T6SS-mediated secretion and target cell killing by Vibrio cholerae and Acinetobacter baylyi. Our results indicate a new model of the T6SS organelle in which the VgrG-PAAR spike complex is decorated with multiple effectors that are delivered simultaneously into target cells in a single contraction-driven translocation event.


Assessment of land use factors associated with dengue cases in Malaysia using Boosted Regression Trees.
The transmission of dengue disease is influenced by complex interactions among vector, host and virus. Land use such as water bodies or certain agricultural practices have been identified as likely risk factors for dengue because of the provision of suitable habitats for the vector. Many studies have focused on the land use factors of dengue vector abundance in small areas but have not yet studied the relationship between land use factors and dengue cases for large regions. This study aims to clarify if land use factors other than human settlements, e.g. different types of agricultural land use, water bodies and forest are associated with reported dengue cases from 2008 to 2010 in the state of Selangor, Malaysia. From the correlative relationship, we aim to generate a prediction risk map. We used Boosted Regression Trees (BRT) to account for nonlinearities and interactions between the factors with high predictive accuracies. Our model with a cross-validated performance score (Area Under the Receiver Operator Characteristic Curve, ROC AUC) of 0.81 showed that the most important land use factors are human settlements (model importance of 39.2%), followed by water bodies (16.1%), mixed horticulture (8.7%), open land (7.5%) and neglected grassland (6.7%). A risk map after 100 model runs with a cross-validated ROC AUC mean of 0.81 (±0.001 s.d.) is presented. Our findings may be an important asset for improving surveillance and control interventions for dengue.


Measuring Organizational Capacity to Accelerate Health Care Innovation in Academic Health Centers.
In an era of rising clinical costs and shrinking federal research dollars, the survival of the academic health center may depend on its capacity to cultivate high-impact innovations in care delivery on an accelerated basis. Yet, the health sciences literature offers little guidance regarding the key organizational determinants most likely to facilitate such innovation. We report on the conceptualization, development, and preliminary testing of a new 21-item Accelerated Healthcare Innovation Capacity scale for addressing that knowledge gap. Instrument development followed a standardized process, including expert panel testing of the new scale's content relevance validity. A sample (N = 53) of academic health center administrators, clinicians, and faculty affiliated with a single organization volunteered to complete the Accelerated Healthcare Innovation Capacity scale in survey form. Data were analyzed to evaluate scale reliability, internal consistency, and construct validity. High-expert agreement (overall S-CVI of 0.91) was obtained on content relevance validity. Cronbach α for the scale was 0.941. Exploratory factor analysis confirmed the theoretical soundness of the scale's conceptual framework, which showed high-impact health care innovation support to be a complex, multidimensional concept involving key facilitating factors across 3 major constructs-that is, Culture, Structure, and Policy-with implications for future research and managerial practice, particularly for staff development educators engaged in evaluating quality management and organizational change strategies.


Prevalence estimates for paratuberculosis adjusted for test variability using Bayesian analysis.
The ELISA tests that are available to detect an infection with Mycobacterium avium subsp. paratuberculosis (MAP) have a limited validity expressed as the sensitivity (Se) and specificity (Sp). In many studies, the Se and Sp of the tests are treated as constants and this will result in an underestimation of the variability of the true prevalence (TP). Bayesian inference provided a natural framework for using information on the test variability (i.e., the uncertainty) in the estimates of test Se and Sp when estimating the TP. Data from two prevalence studies for MAP using an ELISA in several regions in two locations were available for the analyses. In location 1, all cattle of at least 3 years of age were sampled in approximately 90 randomly sampled herds in each of the four regions of the country. In location 2, in 30 randomly sampled herds in each of three regions, approximately 30 randomly selected cows were sampled. Information about the unknown test Se and Sp and MAP prevalence was incorporated into a Bayesian model by joint prior probability distributions. Posterior estimates were obtained by combining the actual likelihood with the prior distributions using Bayes' formula. The corrected cow-level TP (proportion of infected cows in a herd) was low, 5.8 and 3.6% in locations 1 and 2, respectively. Certain regions within a location differed significantly in herd-level TP (proportion of infected herds). The herd-level TP was 54.3% in location 1 (95% credible interval (CI) 46.1, 63.3%) and 32.9% in location 2 (95% CI: 14.4, 73.3%). The variation in the herd-level TP estimate for location 2 was more than three times as large as the variation in location 1 mainly because of the relatively small number of investigated herds in location 2. In future prevalence studies for MAP, sample size calculations should be based on a very low cow-level prevalence. Approximately 50 and 90% of the herds in the current study had an estimated cow-level TP below 4 and 10%, respectively.


Identification of immunogenic antigens from Aspergillus fumigatus by direct multiparameter characterization of specific conventional and regulatory CD4+ T cells.
CD4(+) T cells orchestrate immune responses against fungi, such as Aspergillus fumigatus, a major fungal pathogen in humans. The complexity of the fungal genome and lifestyle questions the existence of one or a few immune-dominant Ags and complicates systematic screening for immunogenic Ags useful for immunotherapy or diagnostics. In this study, we used a recently developed flow cytometric assay for the direct ex vivo characterization of A. fumigatus-specific CD4(+) T cells for rapid identification of physiological T cell targets in healthy donors. We show that the T cell response is primarily directed against metabolically active A. fumigatus morphotypes and is stronger against membrane protein fractions compared with cell wall or cytosolic proteins. Further analysis of 15 selected single A. fumigatus proteins revealed a highly diverse reactivity pattern that was donor and protein dependent. Importantly, the parallel assessment of T cell frequency, phenotype, and function allowed us to differentiate between proteins that elicit strong memory T cell responses in vivo versus Ags that induce T cell exhaustion or no reactivity in vivo. The regulatory T cell (Treg) response mirrors the conventional T cell response in terms of numbers and target specificity. Thus, our data reveal that the fungal T cell immunome is complex, but the ex vivo characterization of reactive T cells allows us to classify Ags and to predict potential immunogenic targets. A. fumigatus-specific conventional T cell responses are counterbalanced by a strong Treg response, suggesting that Treg-depletion strategies may be helpful in improving antifungal immunity.


Screening for depression in young Indigenous people: building on a unique community initiative.
Gurriny Yealamucka Health Service Aboriginal Corporation (GYHSAC) is an Indigenous community-controlled health organisation providing comprehensive primary care to the people of Yarrabah in far north Queensland, Australia. GYHSAC conducts an annual Young Person's Health Check (YPC) for people aged 15-25 years based on the Medical Benefits Schedule Item 715. However, the YPC is constantly evolving to meet the needs of the community, and in 2016, in response to concerns about psychological risk among Indigenous youth, GYHSAC teamed up with James Cook University to trial an adapted PHQ-9 depression screening tool (aPHQ-9) as part of the YPC. This study describes the 2016 YPC event, reports the prevalence of depressive symptoms, examines local issues related to the use of the screening tool and proposes recommendations for future health screening. Experienced health professionals conducted the aPHQ-9 assessment in a private area of the clinic. One-in-five young people were found to have moderate-severe symptoms or self-harm ideation in the previous 2 weeks; they were referred to the mental health service. The aPHQ-9 screening process was found to be straightforward and well accepted by staff and youth. Importantly, it provided valuable 'space' to facilitate communication on sensitive issues and was a conduit for speedy referral and follow up by trained staff. Based on our experience, we recommend dedicated depression screening in future routine community health checks for young people and adults.


Patient review of selected electronic health record data improves visit experience.
Patients are increasingly empowered, informed and active participants in their healthcare. Patients at Partners Healthcare in Boston, MA utilized a web- based portal, Patient Gateway, to submit pre-visit health status information through a journal to their provider. Results of a patient survey indicate that such tools have the potential to improve communication and patient satisfaction, and that the content of information influences the patients visit experience.


Induced Foxp3(+) T Cells Colonizing Tolerated Allografts Exhibit the Hypomethylation Pattern Typical of Mature Regulatory T Cells.
Regulatory T cells expressing the transcription factor Foxp3 require acquisition of a specific hypomethylation pattern to ensure optimal functional commitment, limited lineage plasticity, and long-term maintenance of tolerance. A better understanding of the molecular mechanisms involved in the generation of these epigenetic changes in vivo will contribute to the clinical exploitation of Foxp3(+) Treg. Here, we show that both in vitro and in vivo generated antigen-specific Foxp3(+) Treg can acquire Treg-specific epigenetic characteristics and prevent skin graft rejection in an animal model.


Misrepresentation of neuroscience data might give rise to misleading conclusions in the media: the case of attention deficit hyperactivity disorder.
There is often a huge gap between neurobiological facts and firm conclusions stated by the media. Data misrepresentation in the conclusions and summaries of neuroscience articles might contribute to this gap. Using the case of attention deficit hyperactivity disorder (ADHD), we identified three types of misrepresentation. The first relies on prominent inconsistencies between results and claimed conclusions and was observed in two scientific reports dealing with ADHD. Only one out of the 61 media articles echoing both scientific reports adequately described the results and, thus questioned the claimed conclusion. The second type of misrepresentation consists in putting a firm conclusion in the summary while raw data that strongly limit the claim are only given in the results section. To quantify this misrepresentation we analyzed the summaries of all articles asserting that polymorphisms of the gene coding for the D4 dopaminergic receptor are associated with ADHD. Only 25 summaries out of 159 also mentioned that this association confers a small risk. This misrepresentation is also observed in most media articles reporting on ADHD and the D4 gene. The third misrepresentation consists in extrapolating basic and pre-clinical findings to new therapeutic prospects in inappropriate ways. Indeed, analysis of all ADHD-related studies in mice showed that 23% of the conclusions were overstated. The frequency of this overstatement was positively related with the impact factor of the journal. Data misrepresentations are frequent in the scientific literature dealing with ADHD and may contribute to the appearance of misleading conclusions in the media. In synergy with citation distortions and publication biases they influence social representations and bias the scientific evidence in favor of the view that ADHD is primarily caused by biological factors. We discuss the social consequences and the causes of data misrepresentations and suggest a few corrective actions.


Aggregation kinetics of extended porphyrin and cyanine dye assemblies.
The kinetics of J-aggregate formation has been studied for two chromophores, tetrakis-4-sulfonatophenylporphine in an acid medium and pseudoisocyanine on a polyvinylsulfonate template. The assembly processes differ both in their sensitivity to initiation protocols and in the reaction profiles they produce. The porphyrin's assembly kinetics, for example, displays an induction period unlike that of the cyanine dye. Two kinetic models are presented. For the porphyrin, an autocatalytic pathway in which the formation of an aggregation nucleus is rate-determining appears to be applicable; for the pseudoisocyanine dye, an equation derived for diffusion-limited aggregation of a fractal object satisfactorily fits the data. These models are shown to be useful for the analysis of kinetic data obtained for several biologically important aggregation processes.


Distribution of 5-HT1 binding sites in cat spinal cord.
Quantitative analysis of high affinity [3H]5-HT binding to 5-HT1 receptors in the cervical, thoracic, lumbar, and sacral spinal cord of the cat revealed specific binding throughout the grey matter, with the highest levels of binding in laminae II and III, and the lowest levels in laminae I and VII. Relatively high levels were also observed in the thoracic intermediolateral cell column. There were no significant differences in the degree of binding between various segmental levels. Comparison of these data with published maps of 5-HT immunoreactivity reveals--with the exception of lamina I--a close correspondence between the degree of immunoreactivity and the degree of 5-HT binding. These results suggest that 5-HT plays an important role in a variety of spinal cord sensory, motor and autonomic functions.


Complementary and alternative medicine for the treatment of type 2 diabetes.
To review clinical evidence supporting complementary and alternative medicine interventions for improving glycemic control in type 2 diabetes mellitus. MEDLINE and EMBASE were searched from January 1966 to August 2008 using the term type 2 diabetes in combination with each of the following terms for specific therapies selected by the authors: cinnamon, fenugreek, gymnema, green tea, fibre, momordica, chromium, and vanadium. Only human clinical trials were selected for review. Chromium reduced glycosylated hemoglobin (HbA(1c)) and fasting blood glucose (FBG) levels in a large meta-analysis. Gymnema sylvestre reduced HbA(1c) levels in 2 small open-label trials. Cinnamon improved FBG but its effects on HbA(1c) are unknown. Bitter melon had no effect in 2 small trials. Fibre had no consistent effect on HbA(1c) or FBG in 12 small trials. Green tea reduced FBG levels in 1 of 3 small trials. Fenugreek reduced FBG in 1 of 3 small trials. Vanadium reduced FBG in small, uncontrolled trials. There were no trials evaluating microvascular or macrovascular complications or other clinical end points. Chromium, and possibly gymnema, appears to improve glycemic control. Fibre, green tea, and fenugreek have other benefits but there is little evidence that they substantially improve glycemic control. Further research on bitter melon and cinnamon is warranted. There is no complementary and alternative medicine research addressing microvascular or macrovascular clinical outcomes.


Switching leukemia cell phenotype between life and death.
Divergent life or death responses of a cell can be controlled by a single cytokine (tumor necrosis factor alpha, TNF) via the signaling pathways that respond to activation of its two receptors (TNFR1 and TNFR2). Here, we show that the choice of life or death can be controlled by manipulation of TNFR signals. In human erythroleukemia patient myeloid progenitor stem cells (TF-1) as well as chronic myelogenous leukemia cells (K562), granulocyte-macrophage colony-stimulating factor primes cells for apoptosis. These death-responsive cells show prolonged TNF stimulation of c-Jun N-terminal kinase and p38 mitogen-activated protein kinase, but no NF-kappaB transcriptional activity as a consequence of receptor-interacting protein degradation by caspases. Conversely, cells of a proliferative phenotype display antiapoptotic NF-kappaB responses that antagonize c-Jun N-terminal kinase and p38 mitogen-activated protein kinase stress kinase effects. These proliferative effects of TNF are apparently due to enhanced basal expression of the caspase-8/FLICE-inhibitory protein FLIP. Manipulation of the NF-kappaB, c-Jun N-terminal kinase, or p38 mitogen-activated protein kinase signals switches leukemia cells from a proliferative to an apoptotic phenotype; consequently, these highly proliferative cells die rapidly. In addition, sodium salicylate mimics the death phenotype signals and causes selective destruction of leukemia cells. These findings reveal the signaling mechanisms underlying the phenomenon of human leukemia cell life/death switching. Additionally, through knowledge of the signals that control TNF life/death switching, we have identified several therapeutic targets for selectively killing these cells.


The effect of a Computerised Decision Support System (CDSS) on compliance with the prehospital assessment process: results of an interrupted time-series study.
Errors in the decision-making process are probably the main threat to patient safety in the prehospital setting. The reason can be the change of focus in prehospital care from the traditional "scoop and run" practice to a more complex assessment and this new focus imposes real demands on clinical judgment. The use of Clinical Guidelines (CG) is a common strategy for cognitively supporting the prehospital providers. However, there are studies that suggest that the compliance with CG in some cases is low in the prehospital setting. One possible way to increase compliance with guidelines could be to introduce guidelines in a Computerized Decision Support System (CDSS). There is limited evidence relating to the effect of CDSS in a prehospital setting. The present study aimed to evaluate the effect of CDSS on compliance with the basic assessment process described in the prehospital CG and the effect of On Scene Time (OST). In this time-series study, data from prehospital medical records were collected on a weekly basis during the study period. Medical records were rated with the guidance of a rating protocol and data on OST were collected. The difference between baseline and the intervention period was assessed by a segmented regression. In this study, 371 patients were included. Compliance with the assessment process described in the prehospital CG was stable during the baseline period. Following the introduction of the CDSS, compliance rose significantly. The post-intervention slope was stable. The CDSS had no significant effect on OST. The use of CDSS in prehospital care has the ability to increase compliance with the assessment process of patients with a medical emergency. This study was unable to demonstrate any effects of OST.


Preventing pressure ulcers in hospitals: A systematic review of nurse-focused quality improvement interventions.
A systematic review of the literature on nurse-focused interventions conducted in the hospital setting informs the evidence base for implementation of pressure ulcer (PU) prevention programs. Despite the availability of published guidelines, there is little evidence about which interventions can be successfully integrated into routine care through quality improvement (QI). The two previous literature syntheses on PU prevention have included articles from multiple settings but have not focused specifically on QI. A search of six electronic databases for publications from January 1990 to September 2009 was conducted. Trial registries and bibliographies of retrieved studies and reviews, and Internet sites of funding agencies were also searched. Using standardized forms, two independent reviewers screened publications for eligibility into the sample; data were abstracted and study quality was assessed for those that passed screening. Thirty-nine studies met the inclusion criteria. Most of them used a before-and-after study design in a single site. Intervention strategies included PU-specific changes in combination with educational and/or QI strategies. Most studies reported patient outcome measures, while fewer reported nursing process of care measures. For nearly all the studies, the authors concluded that the intervention had a positive effect. The pooled risk difference for developing PUs was -.07 (95% confidence interval [CI]: -0.0976, -0.0418) comparing the pre- and postintervention status. Future research can build the evidence base for implementation through an increased emphasis on understanding the mechanisms by which improved outcomes are achieved and describing the conditions under which specific intervention strategies are likely to succeed or fail.


Food as Pharma? The Case of Glucosinolates.
Glucosinolates (GLSs) are dietary plant secondary metabolites occurring in the order Brassicales with potential health effects, in particular as anti-carcinogenic compounds. GLSs are converted into a variety of breakdown products (BPs) upon plant tissue damage and by the gut microbiota. GLS biological activity is related to BPs rather than to GLSs themselves. we have reviewed the most recent scientific literature on the metabolic fate and the biological effect of GLSs with particular emphasis on the epidemiological evidence for health effect and evidence from clinical trials. An overview of potential molecular mechanisms underlying GLS biological effect is provided. The potential toxic or anti-nutritional effect has also been discussed. Epidemiological and human in vivo evidence point towards a potential anti-cancer effect for sulforaphane, indole-3-carbinol and 3,3-diindolylmethane. A number of new human clinical trials are on-going and will likely shed further light on GLS protective effect towards cancer as well as other diseases. BPs biological effect is the results of a plurality of molecular mechanisms acting simultaneously which include modulation of xenobiotic metabolism, modulation of inflammation, regulation of apoptosis, cell cycle arrest, angiogenesis and metastasis and regulation of epigenetic events. BPs have been extensively investigated for their protective effect towards cancer but in recent years the interest also includes other diseases. It appears that certain BPs may protect against and may even represent a therapeutic strategy against several forms of cancer. Whether this latter effect can be achieved through diet or supplements should be investigated more thoroughly.


Drosophila Mon2 couples Oskar-induced endocytosis with actin remodeling for cortical anchorage of the germ plasm.
Drosophila pole (germ) plasm contains germline and abdominal determinants. Its assembly begins with the localization and translation of oskar (osk) RNA at the oocyte posterior, to which the pole plasm must be restricted for proper embryonic development. Osk stimulates endocytosis, which in turn promotes actin remodeling to form long F-actin projections at the oocyte posterior pole. Although the endocytosis-coupled actin remodeling appears to be crucial for the pole plasm anchoring, the mechanism linking Osk-induced endocytic activity and actin remodeling is unknown. Here, we report that a Golgi-endosomal protein, Mon2, acts downstream of Osk to remodel cortical actin and to anchor the pole plasm. Mon2 interacts with two actin nucleators known to be involved in osk RNA localization in the oocyte, Cappuccino (Capu) and Spire (Spir), and promotes the accumulation of the small GTPase Rho1 at the oocyte posterior. We also found that these actin regulators are required for Osk-dependent formation of long F-actin projections and cortical anchoring of pole plasm components. We propose that, in response to the Osk-mediated endocytic activation, vesicle-localized Mon2 acts as a scaffold that instructs the actin-remodeling complex to form long F-actin projections. This Mon2-mediated coupling event is crucial to restrict the pole plasm to the oocyte posterior cortex.


Causes of fatal childhood accidents involving head injury in northern region, 1979-86.
To examine the causes and circumstances surrounding fatal accidents involving head injuries in children in the Northern region. Retrospective review of the hospital case notes, necropsy reports, and records of the coroners' inquests. Northern Regional Health Authority. All 255 children aged less than 16 years who died with a head injury during 1979-86. Cause of injury and circumstances of accident according to reports of inquests; injury severity score; number of fatal accidents and mortality per 100,000 children in 10 groups of local authority wards ranked according to their score on the overall deprivation index; and distance of site of accident from child's home. Of the 255 children who died after a head injury, 136 (53%) children were playing at the time of the accident. 195 (76%) children sustained the head injury in road traffic accidents, 135 as pedestrians, 35 as cyclists, and 25 as passengers in a vehicle. In 120 accidents in child pedestrians the primary cause of accident was the unsafe behaviour of the child. 172 (67%) accidents occurred within one to two km of the child's home and 153 (63%) between 3 pm and 9 pm. The mortality was significantly related to social deprivation; excluding eight children injured while on holiday in the region, 15-fold decrease in mortality was recorded between the local authority wards that ranked highest on the overall deprivation index and those that ranked lowest (14.0/100,000 children, group 10 v 0.9/100,000, group 1 respectively, p less than 0.00001). The finding that most accidents occurred in children living in deprived areas who were playing unsupervised near their home suggests that childhood mortality might be appreciably reduced if children at play were protected from traffic, particularly in socially deprived areas.


Activated bauxite waste as an adsorbent for removal of Acid Blue 92 from aqueous solutions.
Bauxite waste, known as red mud, is produced in some industrial processes, such as aluminum production process. In this process, the waste material is produced from leached bauxite as a by product. In this research, the removal of Acid Blue 92 (AB92) dye was investigated from aqueous solution onto the activated bauxite waste (red mud) in a batch equilibration system. Besides, the influences of pH, adsorbent dosage, contact time, initial concentration of dye and temperature have been considered. It was found that the OH group is an effective functional group for the adsorption process. The intensity of the peaks correspond to OH group has been significantly climbed after the activation process. The adsorption kinetics of AB92 can be well described by the pseudo-second-order reaction model. Based on the isotherm data obtained from the fittings of the adsorption kinetics, the Langmuir model appears to fit the adsorption process better than the Freundlich and Brunauer-Emmett-Teller (BET) models.


The description-experience gap in risky choice in nonhuman primates.
Risk attitudes in humans depend on the format used to present the gamble: we are more risk-averse for common gambles in the gains domain whose properties are described to us verbally than for those whose properties we learned about solely through experience. This difference, which constitutes part of the description-experience gap, is important, because it highlights the role of knowledge acquisition in decision-making. The reasons for the gap remain obscure, but could depend upon uniquely human cognitive abilities, such as those associated with language. Thus, the gap may or may not extend to nonhuman animals. For this study, rhesus monkeys performed a novel task in which the properties of some gambles were explicitly cued (described), whereas others were learned through previous choices (experienced). Our monkeys displayed a description-experience gap. Overall, monkeys were more risk-seeking for experienced than for described gambles. This difference was observed for a range of gamble probabilities (from 20% to 80% likelihood of payoff), indicating that it is not limited to low probability events. These results suggest that the description-experience gap does not depend on uniquely human cognitive abilities, such as those associated with language, and support the idea that epistemic influences on risk attitudes are evolutionarily ancient.


CDK1 inactivation regulates anaphase spindle dynamics and cytokinesis in vivo.
Through association with CDK1, cyclin B accumulation and destruction govern the G2/M/G1 transitions in eukaryotic cells. To identify CDK1 inactivation-dependent events during late mitosis, we expressed a nondestructible form of cyclin B (cyclin BDelta90) by microinjecting its mRNA into prometaphase normal rat kidney cells. The injection inhibited chromosome decondensation and nuclear envelope formation. Chromosome disjunction occurred normally, but anaphase-like movement persisted until the chromosomes reached the cell periphery, whereupon they often somersaulted and returned to the cell center. Injection of rhodamine-tubulin showed that this movement occurred in the absence of a central anaphase spindle. In 82% of cells cytokinesis was inhibited; the remainder split themselves into two parts in a process reminiscent of Dictyostelium cytofission. In all cells injected, F-actin and myosin II were diffusely localized with no detectable organization at the equator. Our results suggest that a primary effect of CDK1 inactivation is on spindle dynamics that regulate chromosome movement and cytokinesis. Prolonged CDK1 activity may prevent cytokinesis through inhibiting midzone microtubule formation, the behavior of proteins such as TD60, or through the phosphorylation of myosin II regulatory light chain.


The Killer Fly Hunger Games: Target Size and Speed Predict Decision to Pursuit.
Predatory animals have evolved to optimally detect their prey using exquisite sensory systems such as vision, olfaction and hearing. It may not be so surprising that vertebrates, with large central nervous systems, excel at predatory behaviors. More striking is the fact that many tiny insects, with their miniscule brains and scaled down nerve cords, are also ferocious, highly successful predators. For predation, it is important to determine whether a prey is suitable before initiating pursuit. This is paramount since pursuing a prey that is too large to capture, subdue or dispatch will generate a substantial metabolic cost (in the form of muscle output) without any chance of metabolic gain (in the form of food). In addition, during all pursuits, the predator breaks its potential camouflage and thus runs the risk of becoming prey itself. Many insects use their eyes to initially detect and subsequently pursue prey. Dragonflies, which are extremely efficient predators, therefore have huge eyes with relatively high spatial resolution that allow efficient prey size estimation before initiating pursuit. However, much smaller insects, such as killer flies, also visualize and successfully pursue prey. This is an impressive behavior since the small size of the killer fly naturally limits the neural capacity and also the spatial resolution provided by the compound eye. Despite this, we here show that killer flies efficiently pursue natural (Drosophila melanogaster) and artificial (beads) prey. The natural pursuits are initiated at a distance of 7.9 ± 2.9 cm, which we show is too far away to allow for distance estimation using binocular disparities. Moreover, we show that rather than estimating absolute prey size prior to launching the attack, as dragonflies do, killer flies attack with high probability when the ratio of the prey's subtended retinal velocity and retinal size is 0.37. We also show that killer flies will respond to a stimulus of an angular size that is smaller than that of the photoreceptor acceptance angle, and that the predatory response is strongly modulated by the metabolic state. Our data thus provide an exciting example of a loosely designed matched filter to Drosophila, but one which will still generate successful pursuits of other suitable prey.


Modelling the effects of glucagon during glucose tolerance testing.
Glucose tolerance testing is a tool used to estimate glucose effectiveness and insulin sensitivity in diabetic patients. The importance of such tests has prompted the development and utilisation of mathematical models that describe glucose kinetics as a function of insulin activity. The hormone glucagon, also plays a fundamental role in systemic plasma glucose regulation and is secreted reciprocally to insulin, stimulating catabolic glucose utilisation. However, regulation of glucagon secretion by α-cells is impaired in type-1 and type-2 diabetes through pancreatic islet dysfunction. Despite this, inclusion of glucagon activity when modelling the glucose kinetics during glucose tolerance testing is often overlooked. This study presents two mathematical models of a glucose tolerance test that incorporate glucose-insulin-glucagon dynamics. The first model describes a non-linear relationship between glucagon and glucose, whereas the second model assumes a linear relationship. Both models are validated against insulin-modified and glucose infusion intravenous glucose tolerance test (IVGTT) data, as well as insulin infusion data, and are capable of estimating patient glucose effectiveness (sG) and insulin sensitivity (sI). Inclusion of glucagon dynamics proves to provide a more detailed representation of the metabolic portrait, enabling estimation of two new diagnostic parameters: glucagon effectiveness (sE) and glucagon sensitivity (δ). The models are used to investigate how different degrees of pax'tient glucagon sensitivity and effectiveness affect the concentration of blood glucose and plasma glucagon during IVGTT and insulin infusion tests, providing a platform from which the role of glucagon dynamics during a glucose tolerance test may be investigated and predicted.


Hydrodynamic mobility of chiral colloidal aggregates.
A recent advance in colloidal technology [Zerrouki, Nature (London) 455, 380 (2008)] uses magnetic aggregation to enable the formation of micron-scale particle clusters with helical symmetry. The basic building blocks of these aggregates are doublets composed of two micron-scale beads of different radii bonded together by a magnetic cement. Such self-assembled structures offer potential for controllable transport and separation in a low Reynolds number environment using externally applied magnetic or electric fields. Establishing the hydrodynamic properties of the aggregates, in particular the coupling between rotation and translation afforded by the cluster geometry, is an essential initial step toward the design of microfluidic devices employing these aggregates. To quantify this coupling, we first determine parametrized expressions that describe the positions of the beads in an aggregate as a function of size ratio of the two beads composing the doublets. With the geometry of the structure known, we perform hydrodynamic calculations to ascertain entries of the mobility matrix for the aggregate and establish the relationship between the applied torque about the helical axis and translations parallel to this direction. We find that for larger values of the particle radius ratio the coupling between rotations and translations changes sign as the number of doublets in the aggregate increases. This feature indicates that the clusters possess a more complex superhelical structure.


Immunoregulation of Bone Marrow-Derived Mesenchymal Stem Cells on the Chronic Cigarette Smoking-Induced Lung Inflammation in Rats.
Impact of bone mesenchymal stem cell (BMSC) transfusion on chronic smoking-induced lung inflammation is poorly understood. In this study, a rat model of smoking-related lung injury was induced and the rats were treated with vehicle or BMSCs for two weeks. Different subsets of CD4+ T cells, cytokines, and anti-elastin in the lungs as well as the lung injury were characterized. Serum and lung inducible nitric oxide synthase (iNOS) and STAT5 phosphorylation in lymphocytes from lung tissue were also analyzed. Results indicated that transfusion of BMSCs significantly reduced the chronic smoking-induced lung injury, inflammation, and levels of lung anti-elastin in rats. The frequency of Th1 and Th17 cells and the levels of IL-2, IL-6, IFN-γ, TNF-α, IL-17, IP-10, and MCP-1 increased, but the frequency of Tregs and IL-10 decreased. Transfusion of BMSCs significantly modulated the imbalance of immune responses by mitigating chronic smoking-increased Th1 and Th17 responses, but enhancing Treg responses in the lungs of rats. Transfusion of BMSCs limited chronic smoking-related reduction in the levels of serum and lung iNOS and mitigated smoking-induced STAT5 phosphorylation in lymphocytes from lung tissue. BMSCs negatively regulated smoking-induced autoimmune responses in the lungs of rats and may be promising for the intervention of chronic smoking-related lung injury.


High genetic diversity, phenotypic plasticity, and invasive potential of a recently introduced calcareous sponge, fast spreading across the Atlanto-Mediterranean basin.
Sponges are considered poor invaders, and no genetic studies on introduced sponges have been performed up to now. Paraleucilla magna is the first calcareous sponge introduced to the Mediterranean and Northeastern Atlantic. The study aimed at investigating the genetic makeup and connectivity of the introduced populations of P. magna and at exploring signs of local phenotypic adaptation, to gain insight on the species invasive potential. Ten populations along the species introduction range (Brazil, Açores, Madeira, and continental Europe) were genetically characterized by using nine microsatellite markers. Most populations were genetically structured as suggested by significant Dst and Fst values, significant differences among populations (AMOVA) and the presence of private alleles. The analyzed populations belonged to three genetically homogeneous groups (K) according to the Bayesian algorithm (structure software) and the UPGMA dendrogram. Genetic diversity within populations was higher than expected. Recurrent introductions of non-randomly selected individuals from the native sources may have contributed to the heterozygote deficit found in all populations by forming pedigree structures with mating among relatives. Moreover, the species biological cycle was monitored in a population established on native Mediterranean assemblages (41°40'27″N, 2°47'25″E) and compared with the species cycle in other habitats. Contrasting life spans, growth habits, and reproduction cycles, depending on the habitat conditions, were recorded. To summarize, high genetic diversity, phenotypic local adaptation, and high reproduction rates altogether allow predicting the fast proliferation of P. magna in newly colonized regions and point to its strong invasive potential.


Improved medium for fluconazole susceptibility testing of Candida albicans.
We have compared fluconazole susceptibilities of 92 clinical isolates of Candida albicans by broth microdilution in two different media: standard RPMI 1640 (RPMI) and the same medium supplemented with 18 g of glucose per liter (RPMI-glucose). Preparation of media, drugs, and inocula, as well as incubation conditions, followed the preliminary recommendations of the National Committee for Clinical Laboratory Standards (Villanova, Pa.) antifungal agent working group for broth macrodilution tests with antifungal agents, adapted to microdilution. Microtiter plates were agitated for 5 min before spectrophotometric readings were performed with an automatic plate reader set at 405 mm. The MIC endpoint was defined as an inhibitory concentration calculated from the turbidimetric data as a function of the turbidity in the drug-free control wells. The mean absorbances in the drug-free wells in RPMI and RPMI-glucose were, respectively, 0.38 (41.6% transmission) and 0.99 (10.2% transmission) (P < 0.001; Student's t test). Despite the increased growth in RPMI-glucose, 98.9% of the C. albicans strains tested for fluconazole susceptibility yielded similar MICs (+/- 1 dilution) in both media. Moreover, strains with decreased susceptibility to fluconazole displaying similar MICs in both media are easier to detect in RPMI-glucose because of the greater differences between turbidimetric readings in wells with grown or fluconazole-inhibited cultures. This objective turbidimetric method, with an easy-to-read improved medium (RPMI with glucose), together with previous experience of the National Committee for Clinical Laboratory Standards antifungal agent subcommittee, could overcome some of the present problems associated with lack of reproducibility of azole susceptibility testing.


Influence of acidifying or alkalinizing diets on bone mineral density and urine relative supersaturation with calcium oxalate and struvite in healthy cats.
To evaluate the influence of acidifying or alkalinizing diets on bone mineral density and urine relative supersaturation (URSS) with calcium oxalate and struvite in healthy cats. 6 castrated male and 6 spayed female cats. 3 groups of 4 cats each were fed diets for 12 months that differed only in acidifying or alkalinizing properties (alkalinizing, neutral, and acidifying). Body composition was estimated by use of dual energy x-ray absorptiometry, and 48-hour urine samples were collected for URSS determination. Urine pH differed significantly among diet groups, with the lowest urine pH values in the acidifying diet group and the highest values in the alkalinizing diet group. Differences were not observed in other variables except urinary ammonia excretion, which was significantly higher in the neutral diet group. Calcium oxalate URSS was highest in the acidifying diet group and lowest in the alkalinizing diet group; struvite URSS was not different among groups. Diet was not significantly associated with bone mineral content or density. Urinary undersaturation with calcium oxalate was achieved by inducing alkaluria. Feeding an alkalinizing diet was not associated with URSS with struvite. Bone mineral density and calcium content were not adversely affected by diet; therefore, release of calcium from bone caused by feeding an acidifying diet may not occur in healthy cats.


Viral expression cassette elements to enhance transgene target specificity and expression in gene therapy.
Over the last five years, the number of clinical trials involving AAV (adeno-associated virus) and lentiviral vectors continue to increase by about 150 trials each year. For continued success, AAV and lentiviral expression cassettes need to be designed to meet each disease's specific needs. This review discusses how viral vector expression cassettes can be engineered with elements to enhance target specificity and increase transgene expression. The key differences relating to target specificity between ubiquitous and tissue-specific promoters are discussed, as well as how endogenous miRNAs and their target sequences have been used to restrict transgene expression. Specifically, relevant studies indicating how cis-acting elements such as introns, WPRE, polyadenylation signals, and the CMV enhancer are highlighted to show their utility for enhancing transgene expression in gene therapy applications. All discussion bears in mind that expression cassettes have space constraints. In conclusion, this review can serve as a menu of vector genome design elements and their cost in terms of space to thoughtfully engineer viral vectors for gene therapy.


Anatomical and biomechanical traits of broiler chickens across ontogeny. Part II. Body segment inertial properties and muscle architecture of the pelvic limb.
In broiler chickens, genetic success for desired production traits is often shadowed by welfare concerns related to musculoskeletal health. Whilst these concerns are clear, a viable solution is still elusive. Part of the solution lies in knowing how anatomical changes in afflicted body systems that occur across ontogeny influence standing and moving. Here, to demonstrate these changes we quantify the segment inertial properties of the whole body, trunk (legs removed) and the right pelvic limb segments of five broilers at three different age groups across development. We also consider how muscle architecture (mass, fascicle length and other properties related to mechanics) changes for selected muscles of the pelvic limb. All broilers used had no observed lameness, but we document the limb pathologies identified post mortem, since these two factors do not always correlate, as shown here. The most common leg disorders, including bacterial chondronecrosis with osteomyelitis and rotational and angular deformities of the lower limb, were observed in chickens at all developmental stages. Whole limb morphology is not uniform relative to body size, with broilers obtaining large thighs and feet between four and six weeks of age. This implies that the energetic cost of swinging the limbs is markedly increased across this growth period, perhaps contributing to reduced activity levels. Hindlimb bone length does not change during this period, which may be advantageous for increased stability despite the increased energetic costs. Increased pectoral muscle growth appears to move the centre of mass cranio-dorsally in the last two weeks of growth. This has direct consequences for locomotion (potentially greater limb muscle stresses during standing and moving). Our study is the first to measure these changes in the musculoskeletal system across growth in chickens, and reveals how artificially selected changes of the morphology of the pectoral apparatus may cause deficits in locomotion.


Inhibition of nucleoside transport proteins by C8-alkylamine-substituted purines.
4-nitrobenzylthioinosine (NBTI, 1) is a well-known inhibitor for the nucleoside transport protein ENT1. Here we report on the synthesis and the biological evaluation of compounds that are less polar than NBTI. Compound screening in our laboratory indicated that introduction of an alkylamine substituent at the C(8)-position of N(6)-cyclopentyladenosine (CPA, 2) led to an increment in affinity for the transport protein. It was investigated whether this would also apply for NBTI derivatives. Two series of C(8)-alkylamine-substituted compounds were prepared, one in which the nitro group was absent (46-58) and another in which the ribose moiety was replaced by a benzyl group (72-75). Comparison of the biological data of these compounds with 6-benzylthioinosine (4, K(i) = 53 nM) and 9-benzyl-6-(4-nitrobenzylsulfanyl)purine (59, K(i) = 135 nM) confirmed the hypothesis. The K(i) values improved upon elongation of the alkylamine chain from methylamine to n-hexylamine with an optimum for n-pentylamine (50, K(i) = 2.3 nM). Substitution with 2-methylbutylamine (52), cyclopropylamine (53), cyclopentylamine (54, 72), and cyclohexylamine (55, 73) revealed that the presence of a bulky group enhanced the affinity. The presence of tertiary amines obtained by substitution with pyrrolidine, piperidine, and morpholine gave only poor results. For both series substitution with cyclopentylamine was most effective. Compound 54 (LUF5942) proved the most active, showing a comparable affinity (K(i) = 0.64 nM) to NBTI but a significantly lower polar surface area.


Ciliary neurotropic factor, interleukin 11, leukemia inhibitory factor, and oncostatin M are growth factors for human myeloma cell lines using the interleukin 6 signal transducer gp130.
Interleukin 6 (IL-6) is a major growth factor for tumor plasma cells involved in human multiple myeloma (MM). In particular, human myeloma cell lines (HMCL), whose growth is completely dependent on addition of exogenous IL-6, can be obtained reproducibly from every patient with terminal disease. Four cytokines, ciliary neurotropic factor (CNTF), IL-11, leukemia inhibitory factor (LIF), and oncostatin M (OM), use the same transducer chain (signal transducer gp130) as IL-6 and share numerous biological activities with this IL. We found that these four cytokines stimulated proliferation and supported the long-term growth of two out of four IL-6-dependent HMCL obtained in our laboratory. Half-maximal proliferation was obtained with cytokine concentrations ranging from 0.4 to 1.2 ng/ml for IL-11, LIF, and OM. CNTF worked at high concentrations only (90 ng/ml), but addition of soluble CNTF receptor increased sensitivity to CNTF 30-fold. The growth-promoting effect of these four cytokines was abrogated by anti-gp130 antibodies, contrary to results for anti-IL-6 receptor or anti-IL-6 antibodies. No detectable changes in the morphology and phenotype were found when myeloma cells were cultured with one of these four cytokines instead of IL-6. Concordant with their IL-6-dependent growth, the four HMCL expressed membrane IL-6R and gp130 detected by FACS analysis. LIF-binding chain gene (LIFR) was expressed only in the two HMCL responsive to LIF and OM.


Hermaphroditism: cytogenetics, gonadal pathology and gender assignment: a case report.
True hermaphroditism is a rare intersex disorder in which individuals possess both testicular and ovarian gonadal tissue. A case of true unilateral hermaphroditism presenting with ambiguous external genitalia, right scrotal testis and left pelvic ovotestis is herein outlined Phallic, gonadal and genetic factors were considered before male gender was assigned. Gender assignment procedures have been questioned by intersex activists opposed to early genital surgery. Western societies have a binary perspective on gender and this leads to a stigma being placed on intersex cases. A multidisciplinary approach to this problem involving paediatric specialists in the field, of endocrinology, surgery and psychiatry is necessary, along with educational programmes that promote tolerance in society to variations in gender.


Impact of a modified Broviac maintenance care bundle on bloodstream infections in paediatric cancer patients.
During intensive chemotherapy, bloodstream infection (BSI) represents an important complication in paediatric cancer patients. Most patients carry a long-term central venous access device (CVAD). Improved maintenance care of these vascular catheters may decrease the risk of BSI. Intervention study (adapted CVAD prevention protocol) with two observation periods (P1: 09-2009 until 05-2011; P2: 09-2011 until 05-2013); prospective surveillance of all laboratory confirmed BSIs. In P2, ready to use sterile NaCl 0.9% syringes were used for CVAD flushing and octenidine/isopropanol for the disinfection of catheter hubs and 3-way stopcocks. During P1, 84 patients were included versus 81 patients during P2. There were no significant differences between the two patient populations in terms of median age, gender, underlying malignancy or disease status (first illness or relapse). Nearly all CVADs were Broviac catheters. The median duration from implantation to removal of the CVAD was 192 days (Inter-quartile-range (IQR); 110-288 days) in P1 and 191 days (IQR; 103-270 days) in P2. 28 BSI were diagnosed in 22 patients in P1 (26% of all patients experienced at least one BSI) and 15 BSI in 12 patients in P2 (15% of all patients). The corresponding results for incidence density (ID) were 0.44 (CI95 0.29-0.62) for P1 vs. 0.34 (0.19-0.53) BSI per 100 inpatient days for P2 and for incidence rate (IR) 7.76 (5.16-10.86) in P1 vs. 4.75 (2.66-7.43) BSI per 1,000 inpatient CVAD utilization days. In P1, 9 BSI were caused by CoNS vs. only 2 in P2 (IR 2.49; CI95 0.17-4.17 vs. 0.63; CI95 0.08-1.72). In P1 two BSI (7%) lead to early removal of the device. During P2 one CVAD was prematurely removed due to a Broviac-related BSI (6.7%). The preventive protocol investigated in this study led to a reduction of BSI in paediatric cancer patients. This result was clinically relevant but - due to insufficient power in a single centre observation - the difference did not reach statistical significance. The most pronounced trend in BSI reduction was observed for CoNS infections. Thus, improving maintenance care of the CVAD may result in lower CVAD-linked infection rates. The higher acquisition cost of the ready to use NaCl 0.9% flushing syringes and octenidine/propanol hub disinfection were probably balanced by cost savings in the intervention period.


Low-coherent light-source angular interferometer using a square prism and the angular-scanning technique.
An interferometer based on using low-coherent light source, a square prism, and the angular-scanning technique is proposed for absolute angular-displacement determinations. An angular displacement of the square prism shifts the correlogram, which is modulated by an envelope function, of the interference signal of the beams passing through the prism. This angle can thus be discovered by detecting the shifting of the envelope peak. A setup constructed to validate the interferometer is used. The results of using this setup are then presented.


Urate oxidase from Aspergillus flavus: new crystal-packing contacts in relation to the content of the active site.
Urate oxidase from Aspergillus flavus (uricase or Uox; EC 18.104.22.168) is a 135 kDa homotetramer with a subunit consisting of 301 amino acids. It catalyses the first step of the degradation of uric acid into allantoin. The structure of the extracted enzyme complexed with a purine-type inhibitor (8-azaxanthin) had been solved from high-resolution X-ray diffraction of I222 crystals. Expression of the recombinant enzyme in Saccharomyces cerevisiae followed by a new purification procedure allowed the crystallization of both unliganded and liganded enzymes utilizing the same conditions but in various crystal forms. Here, four different crystal forms of Uox are analyzed. The diversity of the Uox crystal forms appears to depend strongly on the chemicals used as inhibitors. In the presence of uracil and 5,6-diaminouracil crystals usually belong to the trigonal space group P3(1)21, the asymmetric unit (AU) of which contains one tetramer of Uox (four subunits). Chemical oxidation of 5,6-diaminouracil within the protein may occur, leading to the canonical (I222) packing with one subunit per AU. Coexistence of two crystal forms, P2(1) with two tetramers per AU and I222, was found in the same crystallization drop containing another inhibitor, guanine. Finally, a fourth form, P2(1)2(1)2 with one tetramer per AU, resulted fortuitously in the presence of cymelarsan, an additive. Of all the reported forms, the I222 crystal forms present by far the best X-ray diffraction resolution (approximately 1.6 angstroms resolution compared with 2.3-3.2 angstroms for the other forms). The various structures and contacts in all crystalline lattices are compared. The backbones are essentially conserved except for the region near the active site. Its location at the dimer interface is thus likely to be at the origin of the crystal contact changes as a response to the various bound inhibitors.


Prognostic significance of anti-p53 and anti-KRas circulating antibodies in esophageal cancer patients treated with chemoradiotherapy.
P53 mutations are an adverse prognostic factor in esophageal cancer. P53 and KRas mutations are involved in chemo-radioresistance. Circulating anti-p53 or anti-KRas antibodies are associated with gene mutations. We studied whether anti-p53 or anti-KRas auto-antibodies were prognostic factors for response to chemoradiotherapy (CRT) or survival in esophageal carcinoma. Serum p53 and KRas antibodies (abs) were measured using an ELISA method in 97 consecutive patients treated at Saint Louis University Hospital between 1999 and 2002 with CRT for esophageal carcinoma (squamous cell carcinoma (SCCE) 57 patients, adenocarcinoma (ACE) 27 patients). Patient and tumor characteristics, response to treatment and the follow-up status of 84 patients were retrospectively collected. The association between antibodies and patient characteristics was studied. Univariate and multivariate survival analyses were conducted. Twenty-four patients (28%) had anti-p53 abs. Abs were found predominantly in SCCE (p = 0.003). Anti-p53 abs were associated with a shorter overall survival in the univariate analysis (HR 1.8 [1.03-2.9], p = 0.04). In the multivariate analysis, independent prognostic factors for overall and progression-free survival were an objective response to CRT, the CRT strategy (alone or combined with surgery [preoperative]) and anti-p53 abs. None of the long-term survivors had p53 abs. KRas abs were found in 19 patients (23%, no difference according to the histological type). There was no significant association between anti-KRas abs and survival neither in the univariate nor in the multivariate analysis. Neither anti-p53 nor anti-KRas abs were associated with response to CRT. Anti-p53 abs are an independent prognostic factor for esophageal cancer patients treated with CRT. Individualized therapeutic approaches should be evaluated in this population.


Chemoradiotherapy in malignant glioma: standard of care and future directions.
Glioma has been considered resistant to chemotherapy and radiation. Recently, concomitant and adjuvant chemoradiotherapy with temozolomide has become the standard treatment for newly diagnosed glioblastoma. Conversely (neo-)adjuvant PCV (procarbazine, lomustine, vincristine) failed to improve survival in the more chemoresponsive tumor entities of anaplastic oligoastrocytoma and oligodendroglioma. Preclinical investigations suggest synergism or additivity of radiotherapy and temozolomide in glioma cell lines. Although the relative contribution of the concomitant and the adjuvant chemotherapy, respectively, cannot be assessed, the early introduction of chemotherapy and the simultaneous administration with radiotherapy appear to be key for the improvement of outcome. Epigenetic inactivation of the DNA repair enzyme methylguanine methyltransferase (MGMT) seems to be the strongest predictive marker for outcome in patients treated with alkylating agent chemotherapy. Patients whose tumors do not have MGMT promoter methylation are less likely to benefit from the addition of temozolomide chemotherapy and require alternative treatment strategies. The predictive value of MGMT gene promoter methylation is being validated in ongoing trials aiming at overcoming this resistance by a dose-dense continuous temozolomide administration or in combination with MGMT inhibitors. Understanding of molecular mechanisms allows for rational targeting of specific pathways of repair, signaling, and angiogenesis. The addition of tyrosine kinase inhibitors vatalanib (PTK787) and vandetinib (ZD6474), the integrin inhibitor cilengitide, the monoclonal antibodies bevacizumab and cetuximab, the mammalian target of rapamycin inhibitors temsirolimus and everolimus, and the protein kinase C inhibitor enzastaurin, among other agents, are in clinical investigation, building on the established chemoradiotherapy regimen for newly diagnosed glioblastoma.