Risk, clinical features, and outcomes of thrombosis associated with pediatric cardiac surgery.
Thrombosis, usually considered a serious but rare complication of pediatric cardiac surgery, has not been a major clinical and/or research focus in the past. We noted 444 thrombi (66% occlusive, 60% symptomatic) in 171 of 1542 surgeries (11%). Factors associated with increased odds of thrombosis were age <31 days (odds ratio [OR], 2.0; P=0.002), baseline oxygen saturation <85% (OR, 2.0; P=0.001), previous thrombosis (OR, 2.6; P=0.001), heart transplantation (OR, 4.1; P<0.001), use of deep hypothermic circulatory arrest (OR, 1.9 P=0.01), longer cumulative time with central lines (OR, 1.2 per 5-day equivalent; P<0.001), and postoperative use of extracorporeal support (OR, 5.2; P<0.001). Serious complications of thrombosis occurred with 64 of 444 thrombi (14%) in 47 of 171 patients (28%), and were associated with thrombus location (intrathoracic, 45%; extrathoracic arterial, 19%; extrathoracic venous, 8%; P<0.001), symptomatic thrombi (OR, 8.0; P=0.02), and partially/fully occluding thrombi (OR, 14.3; P=0.001); indwelling access line in vessel (versus no access line) was associated with lower risk of serious complications (OR, 0.4; P=0.05). Thrombosis was associated with longer intensive care unit (+10.0 days; P<0.001) and hospital stay (+15.2 days; P<0.001); higher odds of cardiac arrest (OR, 4.9; P<0.001), catheter reintervention (OR, 3.3; P=0.002), and reoperation (OR, 2.5; P=0.003); and increased mortality (OR, 5.1; P<0.001). Long-term outcome assessment was possible for 316 thrombi in 129 patients. Of those, 197 (62%) had resolved at the last follow-up. Factors associated with increased odds of thrombus resolution were location (intrathoracic, 75%; extrathoracic arterial, 89%; extrathoracic venous, 60%; P<0.001), nonocclusive thrombi (OR, 2.2; P=0.01), older age at surgery (OR, 1.2 per year; P=0.04), higher white blood cell count (OR, 1.1/10(9) cells per 1 mL; P=0.002), and lower fibrinogen (OR, 1.4/g/L; P=0.02) after surgery. Thrombosis affects a high proportion of children undergoing cardiac surgery and is associated with suboptimal outcomes. Increased awareness and effective prevention and detection strategies are needed.


iTRAQ-Based Quantitative Proteomic Profiling of Staphylococcus aureus Under Different Osmotic Stress Conditions.
Staphylococcus aureus (S. aureus) is an extremely halotolerant pathogenic bacterium with high osmotic stress tolerance, and it is frequently encountered in aquatic production and preservation. However, the mechanism underlying the extremely high osmotic stress tolerance of S. aureus remains unclear. In this study, the isobaric tags for relative and absolute quantification (iTRAQ) method was used to identify the differentially expressed proteins (DEPs) under different sodium chloride (NaCl) concentrations. Compared with the control group (0% NaCl), the 10 and 20% NaCl groups had 484 DEPs and 750 DEPs, respectively. Compared with the 10% NaCl group, the 20% NaCl group had 361 DEPs. Among the DEPs, proteins involved in fatty acid synthesis, proline/glycine betaine biosynthesis and transportation, stress tolerance, cell wall biosynthesis and the TCA cycle were upregulated, whereas proteins associated with biofilm formation and pathogenic infections were downregulated. The results obtained in this study indicate that under extremely high osmotic stress, modification of the cell membrane structure, increased biosynthesis and transportation of osmotic protectants, and redistribution of energy metabolism contribute to the osmotic stress tolerance of S. aureus, and the infectious ability of the bacteria may be limited. The aim of this study was to provide new insight into how S. aureus tolerates the high-salt conditions involved in aquatic production and preservation.


Mapping the zoonotic niche of Marburg virus disease in Africa.
Marburg virus disease (MVD) describes a viral haemorrhagic fever responsible for a number of outbreaks across eastern and southern Africa. It is a zoonotic disease, with the Egyptian rousette (Rousettus aegyptiacus) identified as a reservoir host. Infection is suspected to result from contact between this reservoir and human populations, with occasional secondary human-to-human transmission. Index cases of previous human outbreaks were identified and reports of infection in animals recorded. These data were modelled within a species distribution modelling framework in order to generate a probabilistic surface of zoonotic transmission potential of MVD across sub-Saharan Africa. Areas suitable for zoonotic transmission of MVD are predicted in 27 countries inhabited by 105 million people. Regions are suggested for exploratory surveys to better characterise the geographical distribution of the disease, as well as for directing efforts to communicate the risk of practices enhancing zoonotic contact. These maps can inform future contingency and preparedness strategies for MVD control, especially where secondary transmission is a risk. Coupling this risk map with patient travel histories could be used to guide the differential diagnosis of highly transmissible pathogens, enabling more rapid response to outbreaks of haemorrhagic fever.


Relationship of nurse burnout with personality characteristics and coping behaviors.
Burnout of nurses at university hospitals was analyzed in relation to their personality characteristics and coping behaviors. A self-administered questionnaire regarding burnout (the Copenhagen Burnout Inventory), work-related stressors (the Nursing Job Stressor Scale), personality characteristics (Short-Form Eysenck Personality Questionnaire-Revised), and coping behaviors (the short Japanese version of Brief COPE) was used. We obtained answers from 778 nurses (response rate: 94.9%), and analyzed 707 female registered nurses. Multiple regression analysis showed that neuroticism was more closely related to personal, work-related, and client-related burnout than extroversion. Covariate structure analysis revealed that among the nurses with high neuroticism and low extroversion, client-related burnout was found to be correlated with stressors in relation to conflict with patients and with positive coping behaviors. Among the nurses with low neuroticism and high extroversion, client-related burnout correlated with the coping behavior of behavioral disengagement and conflict with patients. In both groups, an increase in quantitative workload was associated with a higher score for stressors arising from conflict with patients, leading to client-related burnout. These results suggest that acquisition of skills to cultivate appropriate coping behaviors might be useful for reducing client-related burnout in relation to nurses' personality characteristics. These findings need to be further endorsed by intervention studies.


Immune dysfunction in Niemann-Pick disease type C.
Lysosomal storage diseases are inherited monogenic disorders in which lysosome function is compromised. Although individually very rare, they occur at a collective frequency of approximately one in five thousand live births and usually have catastrophic consequences for health. The lysosomal storage diseases Niemann-Pick disease type C (NPC) is caused by mutations predominantly in the lysosomal integral membrane protein NPC1 and clinically presents as a progressive neurodegenerative disorder. In this article we review data that demonstrate significant dysregulation of innate immunity in NPC, which occurs both in peripheral organs and the CNS. In particular pro-inflammatory responses promote disease progression and anti-inflammatory drugs provide benefit in animal models of the disease and are an attractive target for clinical intervention in this disorder. Niemann-Pick disease type C is a rare, devastating, inherited lysosomal storage disease with a unique cellular phenotype characterized by lysosomal accumulation of sphingosine, various glycosphingolipids and cholesterol and a reduction in lysosomal calcium. In this review we highlight the impact of the disease on innate immune activities in both the central nervous system (CNS) and peripheral tissues and discuss their contributions to pathology and the underlying mechanisms.


A comparison of intrapartum interventions and adverse outcomes by parity in planned freestanding midwifery unit and alongside midwifery unit births: secondary analysis of 'low risk' births in the birthplace in England cohort.
For low risk women, there is good evidence that planned birth in a midwifery unit is associated with a reduced risk of maternal interventions compared with planned birth in an obstetric unit. Findings from the Birthplace cohort study have been interpreted by some as suggesting a reduced risk of interventions in planned births in freestanding midwifery units (FMUs) compared with planned births in alongside midwifery units (AMUs). However, possible differences have not been robustly investigated using individual-level Birthplace data. This was a secondary analysis of data on 'low risk' women with singleton, term, 'booked' pregnancies collected in the Birthplace national prospective cohort study. We used logistic regression to compare interventions and outcomes by parity in 11,265 planned FMU births and 16,673 planned AMU births, adjusted for potential confounders, using planned AMU birth as the reference group. Outcomes considered included adverse perinatal outcomes (Birthplace primary outcome measure), instrumental delivery, intrapartum caesarean section, 'straightforward vaginal birth', third or fourth degree perineal trauma, blood transfusion and maternal admission for higher-level care. We used a significance level of 1% for all secondary outcomes. There was no significant difference in adverse perinatal outcomes between planned AMU and FMU births. The odds of instrumental delivery were reduced in planned FMU births (nulliparous: aOR 0.63, 99% CI 0.46-0.86; multiparous: aOR 0.41, 99% CI 0.25-0.68) and the odds of having a 'straightforward vaginal birth' were increased in planned FMU births compared with planned AMU births (nulliparous: aOR 1.47, 99% CI 1.17-1.85; multiparous: 1.86, 99% CI 1.35-2.57). The odds of intrapartum caesarean section did not differ significantly between the two settings (nulliparous: p = 0.147; multiparous: p = 0.224). The overall pattern of findings suggested a trend towards lower intervention rates and fewer adverse maternal outcomes in planned FMU births compared with planned AMU births. The findings support the recommendation that 'low risk' women can be informed that planned birth in an FMU is associated with a lower rate of instrumental delivery and a higher rate of 'straightforward vaginal birth' compared with planned birth in an AMU; and that outcomes for babies do not appear to differ between FMUs and AMUs.


Hepatitis C virus association with peripheral blood B lymphocytes potentiates viral infection of liver-derived hepatoma cells.
Hepatitis C virus (HCV) primarily replicates within the liver, leading to hepatitis, fibrosis, and hepatocellular carcinoma. Infection is also associated with B-cell abnormalities, suggesting an association of the virus with B cells. The infectious JFH-1 strain of HCV can bind primary and immortalized B cells but fails to establish productive infection. However, B cell-associated virus readily infects hepatoma cells, showing an enhanced infectivity compared with extracellular virus. B cells express the viral receptors CD81, SR-BI, and the C-type lectins DC-SIGN and L-SIGN. Antibodies specific for SR-BI and DC-SIGN/L-SIGN reduced B-cell transinfection, supporting a role for these molecules in B-cell association with HCV. Stimulation of B cells with CD40 ligand and interleukin-4 promoted their ability to transinfect hepatoma cells. B cell-associated virus is resistant to trypsin proteolysis and HCV-specific neutralizing antibodies, consistent with particle internalization. HCV promoted the adhesion of primary B cells to Huh-7 hepatomas, providing a mechanism for B-cell retention in the infected liver. In summary, B cells may provide a vehicle for HCV to persist and transmit to the liver.


The proportion and trend of human immunodeficiency virus infections associated with men who have sex with men from Chinese voluntary blood donors: a systematic review and meta-analysis.
Human immunodeficiency virus (HIV)-positive cases associated with men who have sex with men (MSM) have rapidly increased over the past years. The objective of this study is to comprehensively evaluate the proportions, changing trends, and geographical distribution of MSM-associated HIV cases from Chinese voluntary blood donors by systematically reviewing the available literature. Major English and Chinese research databases were searched for studies reporting study locations, study years, the number of HIV infections among blood donors, and the number of HIV-positive donations associated with MSM in China. The proportion estimates were calculated; subgroup analyses and test for time trend were performed using software of comprehensive meta-analysis. Thirty-four studies met eligibility criteria. The pooled proportion of HIV-positive donations associated with MSM from 2001 to 2012 was 36.5% (95% confidence interval, 29.6%-44.1%). The epidemic was found to be more severe in northeast and north China compared to south China (59.6%; 55.0% vs. 3.8%, respectively). The proportion showed a significantly increasing trend over the study period (10.3% in 2001-2005; 38.6% in 2006-2009; and 47.6% in 2010-2012; trend test chi-square = 16.42, p < 0.001). The relatively high proportion of MSM- associated HIV-positive donors is of concern. Efficient and effective measures focused on public education and improving knowledge of blood safety are needed to prevent this at-risk population from seeking HIV testing through blood donation. It is also imperative to expand the scope of postdonation nucleic acid testing to shorten the window period to improve blood supply safety in China.


Effect of breakfast omission and consumption on energy intake and physical activity in adolescent girls: a randomised controlled trial.
It is not known if breakfast consumption is an effective intervention for altering daily energy balance in adolescents when compared with breakfast omission. This study examined the acute effect of breakfast consumption and omission on free-living energy intake (EI) and physical activity (PA) in adolescent girls. Using an acute randomised cross-over design, forty girls (age 13·3 (sd 0·8) years, BMI 21·5 (sd 5·0) kg/m2) completed two, 3-d conditions in a randomised, counter-balanced order: no breakfast (NB) and standardised (approximately 1962 kJ) breakfast (SB). Dietary intakes were assessed using food diaries combined with digital photographic records and PA was measured via accelerometry throughout each condition. Statistical analyses were completed using repeated-measures ANOVA. Post-breakfast EI was 483 (sd 1309) kJ/d higher in NB v. SB (P=0·025), but total daily EI was 1479 (sd 11311) kJ/d higher in SB v. NB (P<0·0005). Daily carbohydrate, fibre and protein intakes were higher in SB v. NB (P<0·0005), whereas daily fat intake was not different (P=0·405). Effect sizes met the minimum important difference of ≥0·20 for all significant effects. Breakfast manipulation did not affect post-breakfast macronutrient intakes (P≥0·451) or time spent sedentary or in PA (P≥0·657). In this sample of adolescent girls, breakfast omission increased post-breakfast free-living EI, but total daily EI was greater when a SB was consumed. We found no evidence that breakfast consumption induces compensatory changes in PA. Further experimental research is required to determine the effects of extended periods of breakfast manipulation in young people.


A 61-million-person experiment in social influence and political mobilization.
Human behaviour is thought to spread through face-to-face social networks, but it is difficult to identify social influence effects in observational studies, and it is unknown whether online social networks operate in the same way. Here we report results from a randomized controlled trial of political mobilization messages delivered to 61 million Facebook users during the 2010 US congressional elections. The results show that the messages directly influenced political self-expression, information seeking and real-world voting behaviour of millions of people. Furthermore, the messages not only influenced the users who received them but also the users' friends, and friends of friends. The effect of social transmission on real-world voting was greater than the direct effect of the messages themselves, and nearly all the transmission occurred between 'close friends' who were more likely to have a face-to-face relationship. These results suggest that strong ties are instrumental for spreading both online and real-world behaviour in human social networks.


Analysis of the genome sequences of three Drosophila melanogaster spontaneous mutation accumulation lines.
We inferred the rate and properties of new spontaneous mutations in Drosophila melanogaster by carrying out whole-genome shotgun sequencing-by-synthesis of three mutation accumulation (MA) lines that had been maintained by close inbreeding for an average of 262 generations. We tested for the presence of new mutations by generating alignments of each MA line to the D. melanogaster reference genome sequence and then compared these alignments base by base. We determined empirically that at least five reads at a site within each line are required for accurate single nucleotide mutation calling. We mapped a total of 174 single-nucleotide mutations, giving a single nucleotide mutation rate of 3.5 x 10(-9) per site per generation. There were no false positives in a random sample of 40 of these mutations checked by Sanger sequencing. Variation in the numbers of mutations among the MA lines was small and nonsignificant. Numbers of transition and transversion mutations were 86 and 88, respectively, implying that transition mutation rate is close to 2x the transversion rate. We observed 1.5x as many G or C --> A or T as A or T --> G or C mutations, implying that the G or C --> A or T mutation rate is close to 2x the A or T --> G or C mutation rate. The base composition of the genome is therefore not at an equilibrium determined solely by mutation. The predicted G + C content at mutational equilibrium (33%) is similar to that observed in transposable element remnants. Nearest-neighbor mutational context dependencies are nonsignificant, suggesting that this is a weak phenomenon in Drosophila. We also saw nonsignificant differences in the mutation rate between transcribed and untranscribed regions, implying that any transcription-coupled repair process is weak. Of seven short indel mutations confirmed, six were deletions, consistent with the deletion bias that is thought to exist in Drosophila.


RNA interference inhibition of Mus81 reduces mitotic recombination in human cells.
Mus81 is a highly conserved endonuclease with homology to the XPF subunit of the XPF-ERCC1 complex. In yeast Mus81 associates with a second subunit, Eme1 or Mms4, which is essential for endonuclease activity in vitro and for in vivo function. Human Mus81 binds to a homolog of fission yeast Eme1 in vitro and in vivo. We show that recombinant Mus81-Eme1 cleaves replication forks, 3' flap substrates, and Holliday junctions in vitro. By use of differentially tagged versions of Mus81 and Eme1, we find that Mus81 associates with Mus81 and that Eme1 associates with Eme1. Thus, complexes containing two or more Mus81-Eme1 units could function to coordinate substrate cleavage in vivo. Down-regulation of Mus81 by RNA interference reduces mitotic recombination in human somatic cells. The recombination defect is rescued by expression of a bacterial Holliday junction resolvase. These data provide direct evidence for a role of Mus81-Eme1 in mitotic recombination in higher eukaryotes and support the hypothesis that Mus81-Eme1 resolves Holliday junctions in vivo.


Chronic aerobic exercise improves blood pressure dipping status in African American nondippers.
The effects of exercise training on nocturnal blood pressure (BP) dipping status remain unclear. African Americans have the highest prevalence of nondippers compared with other racial/ethnic populations. In this 6-month study we tested the hypothesis that long-term aerobic exercise training would increase the levels of nocturnal BP dipping in African American nondippers. We recruited African Americans who were nondiabetic, nonsmoking, and free from cardiovascular and renal disease. For this analysis, only African Americans with a nondipping profile, defined as those with the absence of a nocturnal decline in systolic or diastolic BP (<10% of daytime values), which was determined by ambulatory BP monitoring, were chosen. A pre-post design was used, with baseline and final evaluation including office blood pressure measurement, 24-h ambulatory blood pressure monitoring, fasted blood sampling, and graded exercise testing. Participants engaged in 6 months of supervised aerobic exercise training (AEXT). Following the AEXT intervention, there were significant increases in systolic BP dipping (baseline: 5.8±3.9% vs. final: 9.4±6.1%, P=0.0055) and pulse pressure dipping (baseline: -3.1±6.6% vs. final: 5.0±12.8%, P=0.0109). Of the 18 participants with a nondipping profile at baseline, eight were nonclassified as nondippers after the AEXT intervention. There were no significant changes in office systolic BP/diastolic BP values following the AEXT intervention. This study suggests that the nondipping pattern of ambulatory BP can be improved by chronic AEXT in African American nondippers, regardless of a change in the 24-h average BP. This finding may be clinically important because of the target organ implication of nondipping nocturnal BP.


Real-time numerical forecast of global epidemic spreading: case study of 2009 A/H1N1pdm.
Mathematical and computational models for infectious diseases are increasingly used to support public-health decisions; however, their reliability is currently under debate. Real-time forecasts of epidemic spread using data-driven models have been hindered by the technical challenges posed by parameter estimation and validation. Data gathered for the 2009 H1N1 influenza crisis represent an unprecedented opportunity to validate real-time model predictions and define the main success criteria for different approaches. We used the Global Epidemic and Mobility Model to generate stochastic simulations of epidemic spread worldwide, yielding (among other measures) the incidence and seeding events at a daily resolution for 3,362 subpopulations in 220 countries. Using a Monte Carlo Maximum Likelihood analysis, the model provided an estimate of the seasonal transmission potential during the early phase of the H1N1 pandemic and generated ensemble forecasts for the activity peaks in the northern hemisphere in the fall/winter wave. These results were validated against the real-life surveillance data collected in 48 countries, and their robustness assessed by focusing on 1) the peak timing of the pandemic; 2) the level of spatial resolution allowed by the model; and 3) the clinical attack rate and the effectiveness of the vaccine. In addition, we studied the effect of data incompleteness on the prediction reliability. Real-time predictions of the peak timing are found to be in good agreement with the empirical data, showing strong robustness to data that may not be accessible in real time (such as pre-exposure immunity and adherence to vaccination campaigns), but that affect the predictions for the attack rates. The timing and spatial unfolding of the pandemic are critically sensitive to the level of mobility data integrated into the model. Our results show that large-scale models can be used to provide valuable real-time forecasts of influenza spreading, but they require high-performance computing. The quality of the forecast depends on the level of data integration, thus stressing the need for high-quality data in population-based models, and of progressive updates of validated available empirical knowledge to inform these models.


Membrane binding of plasmid DNA and endocytic pathways are involved in electrotransfection of mammalian cells.
Electric field mediated gene delivery or electrotransfection is a widely used method in various studies ranging from basic cell biology research to clinical gene therapy. Yet, mechanisms of electrotransfection are still controversial. To this end, we investigated the dependence of electrotransfection efficiency (eTE) on binding of plasmid DNA (pDNA) to plasma membrane and how treatment of cells with three endocytic inhibitors (chlorpromazine, genistein, dynasore) or silencing of dynamin expression with specific, small interfering RNA (siRNA) would affect the eTE. Our data demonstrated that the presence of divalent cations (Ca(2+) and Mg(2+)) in electrotransfection buffer enhanced pDNA adsorption to cell membrane and consequently, this enhanced adsorption led to an increase in eTE, up to a certain threshold concentration for each cation. Trypsin treatment of cells at 10 min post electrotransfection stripped off membrane-bound pDNA and resulted in a significant reduction in eTE, indicating that the time period for complete cellular uptake of pDNA (between 10 and 40 min) far exceeded the lifetime of electric field-induced transient pores (∼10 msec) in the cell membrane. Furthermore, treatment of cells with the siRNA and all three pharmacological inhibitors yielded substantial and statistically significant reductions in the eTE. These findings suggest that electrotransfection depends on two mechanisms: (i) binding of pDNA to cell membrane and (ii) endocytosis of membrane-bound pDNA.


Novel key metabolites reveal further branching of the roquefortine/meleagrin biosynthetic pathway.
Metabolic profiling and structural elucidation of novel secondary metabolites obtained from derived deletion strains of the filamentous fungus Penicillium chrysogenum were used to reassign various previously ascribed synthetase genes of the roquefortine/meleagrin pathway to their corresponding products. Next to the structural characterization of roquefortine F and neoxaline, which are for the first time reported for P. chrysogenum, we identified the novel metabolite roquefortine L, including its degradation products, harboring remarkable chemical structures. Their biosynthesis is discussed, questioning the exclusive role of glandicoline A as key intermediate in the pathway. The results reveal that further enzymes of this pathway are rather unspecific and catalyze more than one reaction, leading to excessive branching in the pathway with meleagrin and neoxaline as end products of two branches.


First Report of Palm Rot of Phoenix spp. Caused by Neodeightonia phoenicum in Greece.
In July 2007, a severe rot was observed on Phoenix dactylifera and P. canariensis palms in the vicinity of Heraklion (Crete), Greece. Initial symptoms were pale, elongated spots that gradually turned to dark brown streaks extending along the leaf base and rachis. In early stages, the upper parts of the leaves usually remained unaffected. Eventually decay and premature death of leaves occurred, followed by terminal bud necrosis. Shoot blights and stalk rots were also observed. A filamentous fungus was consistently isolated onto potato dextrose agar (PDA) from leaf base necrotic lesions. Immersed pycnidial conidiomata on pine needles in culture were multiloculate and dark brown to black. Pycnidial paraphyses were absent. Conidiogenous cells were hyaline, cylindrical, and swollen at base. Conidia were thick-walled, ovoid to ellipsoid, with rounded apex and base; initially hyaline and aseptate, 15.2 ± 0.4 × 11.7 ± 0.3 μm, later becoming dark brown and 1-septate, 21.3 ± 0.4 × 11.8 ± 0.3 μm, with a striate appearance. Total DNA was extracted and used for PCR amplification and sequencing of the ITS1-5.8S-ITS2 region, together with parts of the flanking 18S and 28S rRNA genes (1). The sequence (GenBank Accession No. JX456475) was found 99% identical to Neodeightonia phoenicum ITS sequences (GenBank Accession Nos. EU673338 to EU673340), and was clustered together as a single group with the above sequences with good support by phylogenetic analysis that included representatives of other Neodeightonia species and several other Botryosphaeriaceae members. Based on the morphological, molecular, and phylogenetic analyses, the pathogen was identified as N. phoenicum A. J. L. Phillips & Crous (2) (syn. Diplodia phoenicum (Saccardo) H. S. Fawcett & Klotz), formerly also known as Macrophoma phoenicum Saccardo and Strionemadiplodia phoenicum (Saccardo) Zambettakis. To prove pathogenicity, the petioles of the older leaves of seven 2-year-old seedlings of each of three palms, P. canariensis, P. theophrasti, and Washingtonia filifera were wounded with a sterile scalpel (shallow cuts 0.5 to 1.0 cm wide, made parallel to the surface) and inoculated with agar discs from a 1-week-old PDA culture of the fungus. For controls, PDA discs without fungal mycelium were placed on the wounds of four seedlings of each host. Petiole rot, blight, and leaf necrosis were evident on all inoculated plants 6 weeks post inoculation and the pathogen was consistently reisolated from all three inoculated palm species, whereas no symptoms were observed on control plants. N. phoenicum has repeatedly and globally been reported on P. dactylifera (3). To the best of our knowledge, this is the first report of the occurrence of N. phoenicum infecting Phoenix species in Greece. Palms are extensively used as ornamental trees throughout Greece. A potential spread of palm rot caused by N. phoenicum might have a substantial economic impact and should be urgently addressed through appropriate disease management programs. References: (1) M. P. Pantou et al. Mycol. Res. 109:889, 2005. (2) A. J. L. Phillips et al. Persoonia 21:29, 2008. (3) A. Zaid et al. Chapter XII in: Date palm cultivation, FAO Plant Production and Protection Paper 156 Rev. 1, 2002.


The role of experience-based perceptual learning in the face inversion effect.
Perceptual learning of the type we consider here is a consequence of experience with a class of stimuli. It amounts to an enhanced ability to discriminate between stimuli. We argue that it contributes to the ability to distinguish between faces and recognize individuals, and in particular contributes to the face inversion effect (better recognition performance for upright vs inverted faces). Previously, we have shown that experience with a prototype defined category of checkerboards leads to perceptual learning, that this produces an inversion effect, and that this effect can be disrupted by Anodal tDCS to Fp3 during pre-exposure. If we can demonstrate that the same tDCS manipulation also disrupts the inversion effect for faces, then this will strengthen the claim that perceptual learning contributes to that effect. The important question, then, is whether this tDCS procedure would significantly reduce the inversion effect for faces; stimuli that we have lifelong expertise with and for which perceptual learning has already occurred. Consequently, in the experiment reported here we investigated the effects of anodal tDCS at Fp3 during an old/new recognition task for upright and inverted faces. Our results show that stimulation significantly reduced the face inversion effect compared to controls. The effect was one of reducing recognition performance for upright faces. This result is the first to show that tDCS affects perceptual learning that has already occurred, disrupting individuals' ability to recognize upright faces. It provides further support for our account of perceptual learning and its role as a key factor in face recognition.


The canine heart as an electrocardiographic generator. Dependence on cardiac cell orientation.
Traditionally it is assumed that during cardiac depolarization the macroscopic current generators that produce electrocardiographic voltages can be represented as a uniform double-layer source, coincident with the macroscopic boundary between resting and depolarized cardiac fibers as measured with extracellular electrodes ("uniform" hypothesis). A segment of this boundary is thus considered as a current dipole oriented perpendicular to the boundary. We present evidence that, contrary to the above, the effective dipoles largely parallel the long axes of cardiac fibers ("axial" hypothesis). Calculated potentials in volume conductors differ markedly in the two cases. The magnitudes of rapid local "intrinsic" deflections also differ markedly. In our experiments, potential fields prodlced by stimulation at several cardiac sites and measured magnitudes of intrinsic deflections during normal depolarization and that caused by stimulation support the axial hypothesis and are incompatible with the uniform hypothesis. Our results suggest that axial orientation of sources is sufficiently strong so that predictions assuming the uniform hypothesis would be seriously in error, although the axial theory alone does not exactly describe all the measured potentials. Axial orientation of current generators must be considered in quantitative prediction of electrocardiographic potentials. tfurther study of the geometry of the intracellular depolarization boundary and its relation to fiber direction and to the frequency of lateral intercellular junctions is required to describe the generators exactly.


Glutathione and its antiaging and antimelanogenic effects.
Previous studies showed that supplementation of reduced form of glutathione (GSH, 500 mg/d) has a skin-lightening efficacy in humans. This study was designed to evaluate the influences of both GSH and oxidized form (GSSG), at doses lower than 500 mg/d, on improving skin properties. A randomized, double-blind, placebo-controlled, parallel, three-arm study was conducted. Healthy female subjects were equally randomized into three groups and took GSH (250 mg/d), GSSG (250 mg/d), or placebo orally for 12 weeks. At each visit at baseline and for 12 weeks, skin features including melanin index, wrinkles, and other relevant biophysical properties were measured. Blood samples were collected for safety monitoring. In generalized estimating equation analyses, melanin index and ultraviolet spots of all sites including face and arm when given GSH and GSSG tended to be lower than placebo. At some sites evaluated, subjects who received GSH showed a significant reduction in wrinkles compared with those taking placebo. A tendency toward increased skin elasticity was observed in GSH and GSSG compared with placebo. There were no serious adverse effects throughout the study. We showed that oral glutathione, 250 mg/d, in both reduced and oxidized forms effectively influences skin properties. Overall, glutathione in both forms are well tolerated.


The effect of systematic clinical interventions with cigarette smokers on quit status and the rates of smoking-related primary care office visits.
The United States Public Health Service (USPHS) Guideline for Treating Tobacco Use and Dependence includes ten key recommendations regarding the identification and the treatment of tobacco users seen in all health care settings. To our knowledge, the impact of system-wide brief interventions with cigarette smokers on smoking prevalence and health care utilization has not been examined using patient population-based data. Data on clinical interventions with cigarette smokers were examined for primary care office visits of 104,639 patients at 17 Harvard Vanguard Medical Associates (HVMA) sites. An operational definition of "systems change" was developed. It included thresholds for intervention frequency and sustainability. Twelve sites met the criteria. Five did not. Decreases in self-reported smoking prevalence were 40% greater at sites that achieved systems change (13.6% vs. 9.7%, p<.01). On average, the likelihood of quitting increased by 2.6% (p<0.05, 95% CI: 0.1%-4.6%) per occurrence of brief intervention. For patients with a recent history of current smoking whose home site experienced systems change, the likelihood of an office visit for smoking-related diagnoses decreased by 4.3% on an annualized basis after systems change occurred (p<0.05, 95% CI: 0.5%-8.1%). There was no change in the likelihood of an office visit for smoking-related diagnoses following systems change among non-smokers. The clinical practice data from HVMA suggest that a systems approach can lead to significant reductions in smoking prevalence and the rate of office visits for smoking-related diseases. Most comprehensive tobacco intervention strategies focus on the provider or the tobacco user, but these results argue that health systems should be included as an integral component of a comprehensive tobacco intervention strategy. The HVMA results also give us an indication of the potential health impacts when meaningful use core tobacco measures are widely adopted.


It is always on your mind: experiences and perceptions of falling of older people and their carers and the potential of a mobile falls detection device.
Background. Falls and fear of falling present a major risk to older people as both can affect their quality of life and independence. Mobile assistive technologies (AT) fall detection devices may maximise the potential for older people to live independently for as long as possible within their own homes by facilitating early detection of falls. Aims. To explore the experiences and perceptions of older people and their carers as to the potential of a mobile falls detection AT device. Methods. Nine focus groups with 47 participants including both older people with a range of health conditions and their carers. Interviews were audio recorded, transcribed verbatim, and thematically analysed. Results. Four key themes were identified relating to participants' experiences and perceptions of falling and the potential impact of a mobile falls detector: cause of falling, falling as everyday vulnerability, the environmental context of falling, and regaining confidence and independence by having a mobile falls detector. Conclusion. The perceived benefits of a mobile falls detector may differ between older people and their carers. The experience of falling has to be taken into account when designing mobile assistive technology devices as these may influence perceptions of such devices and how older people utilise them.


High-throughput, Highly Sensitive Analyses of Bacterial Morphogenesis Using Ultra Performance Liquid Chromatography.
The bacterial cell wall is a network of glycan strands cross-linked by short peptides (peptidoglycan); it is responsible for the mechanical integrity of the cell and shape determination. Liquid chromatography can be used to measure the abundance of the muropeptide subunits composing the cell wall. Characteristics such as the degree of cross-linking and average glycan strand length are known to vary across species. However, a systematic comparison among strains of a given species has yet to be undertaken, making it difficult to assess the origins of variability in peptidoglycan composition. We present a protocol for muropeptide analysis using ultra performance liquid chromatography (UPLC) and demonstrate that UPLC achieves resolution comparable with that of HPLC while requiring orders of magnitude less injection volume and a fraction of the elution time. We also developed a software platform to automate the identification and quantification of chromatographic peaks, which we demonstrate has improved accuracy relative to other software. This combined experimental and computational methodology revealed that peptidoglycan composition was approximately maintained across strains from three Gram-negative species despite taxonomical and morphological differences. Peptidoglycan composition and density were maintained after we systematically altered cell size in Escherichia coli using the antibiotic A22, indicating that cell shape is largely decoupled from the biochemistry of peptidoglycan synthesis. High-throughput, sensitive UPLC combined with our automated software for chromatographic analysis will accelerate the discovery of peptidoglycan composition and the molecular mechanisms of cell wall structure determination.


Self-textured oxide structure for improved performance of 365 nm ultraviolet vertical-type light-emitting diodes.
High performance 365 nm vertical-type ultraviolet light-emitting diodes (LEDs) are demonstrated by the insertion of a self-textured oxide mask (STOM) structure using metal-organic chemical vapor deposition. The dislocation densities were reduced significantly via the STOM by the observation of the transmission electron microcopy image. Under an injection current of 20 mA, a 50% light output power enhancement was achieved, representing an enhancement of 35.4% in light extraction efficiency and injected electron efficiency of the LED with STOM in comparison to that without STOM. At 350 mA, the light output power of the STOM-LEDs was approximately 24.4% higher. Measurements of the optical and electrical properties of the LED showed that the corrugated STOM structure improved the light scattering and reflection which increased the light output, and also enhanced the current spreading to intensify radiative recombination.


Surgical Treatment of Double Outlet Right Ventricle Complicated by Pulmonary Hypertension.
Double outlet right ventricle (DORV) is a group of complex congenital heart abnormalities. Preoperative pulmonary hypertension (PH) is considered an important risk factor for early death during the surgical treatment of DORV. The aim of this study was to report our experience on surgical treatment of DORV complicated by PH. From June 2004 to November 2016, 61 patients (36 males and 25 females) aged 2 weeks to 26 years (median: 0.67 years and interquartile range: 0.42-1.67 years) with DORV (two great arteries overriding at least 50%) complicated by PH underwent surgical treatment in our center. All patients were categorized according to surgical age and lesion type, respectively. Pulmonary artery systolic pressure (PASP), pulmonary artery diastolic pressure (PADP), and mean pulmonary artery pressure (mPAP) were measured directly before cardiopulmonary bypass (CPB) was established and after CPB was removed. An intracardiac channel procedure was performed in 37 patients, arterial switch procedure in 19 patients, Rastelli procedure in three patient, Senning procedure in one patients, and Mustard procedure in one patient. The Student's t-test and Chi-squared test were performed to evaluate clinical outcomes of the surgical timing and operation choice. Fifty-five patients had uneventful recovery. PASP fell from 55.3 ± 11.2 mmHg to 34.7 ± 11.6 mmHg (t = 14.05, P < 0.001), PADP fell from 29.7 ± 12.5 mmHg to 18.6 ± 7.9 mmHg (t = 7.39, P < 0.001), and mPAP fell from 40.3 ± 10.6 mmHg to 25.7 ± 8.3 mmHg (t = 11.85, P < 0.001). Six (9.8%) patients died owing to complications including low cardiac output syndrome in two patients, respiratory failure in two, pulmonary hemorrhage in one, and sudden death in one patient. Pulmonary artery pressure (PAP) dropped significantly in infant and child patients. Mortality of both infants (13.9%) and adults (33.3%) was high. PAP of patients with DORV complicated by PH can be expected to fall significantly after surgery. An arterial switch procedure can achieve excellent results in patients with transposition of the great arteries type. Higher incidence of complications may occur in patients with ventricular septal defect (VSD) type before 1 year of age. For those with remote VSD type, VSD enlargement and right ventricle outflow tract reconstruction are usually required with acceptable results. The degree of aortic overriding does not influence surgical outcome.


Intraspecific Differentiation of Vibrio vulnificus Biotypes by Amplified Fragment Length Polymorphism and Ribotyping.
The intraspecific genomic relatedness of 80 Vibrio vulnificus isolates, 44 of biotype 1 and 36 of biotype 2, from different geographic origins and sources was evaluated by ribotyping and AFLP (amplified fragment length polymorphism) fingerprinting. Ribopatterns of DNAs digested with KpnI and hybridized with an oligonucleotide complementary to a highly conserved sequence in the 23S rRNA gene revealed up to 19 ribotypes in the species, which were different for the two biotypes. Sixteen different ribotypes were found within biotype 1 strains from clinical and environmental sources, and only three, recovered mainly from diseased eels, were found within biotype 2. Within this biotype, 96% of the strains showed the same ribopattern. The closest similarity was shown by the strains coming from the same eel farm, irrespectively of biotype. AFLP fingerprints obtained by selective PCR amplification of HindIII-TaqI double-restricted DNA fragments exhibited a strain-specific pattern which allowed the finest differentiation of subgroups within the eel-pathogenic isolates sharing the same ribopattern. Both techniques revealed good genetic markers for intraspecific differentiation of V. vulnificus. Ribotyping clearly separated the eel-pathogenic strains from the clinical and environmental isolates, whereas AFLP enabled the monitoring of individual strains and therefore constitutes one of the most discriminative tools for epidemiological and ecological studies.


Tight modulation of Escherichia coli bacterial biofilm formation through controlled expression of adhesion factors.
Despite the economic and sanitary problems caused by harmful biofilms, biofilms are nonetheless used empirically in industrial environmental and bioremediation processes and may be of potential use in medical settings for interfering with pathogen development. Escherichia coli is one of the bacteria with which biofilm formation has been studied in great detail, and it is especially appreciated for biotechnology applications because of its genetic amenability. Here we describe the development of two new genetic tools enabling the constitutive and inducible expression of any gene or operon of interest at its native locus. In addition to providing valuable tools for complementation and overexpression experiments, these two compact genetic cassettes were used to modulate the biofilm formation capacities of E. coli by taking control of two biofilm-promoting factors, autotransported antigen 43 adhesin and the bscABZC cellulose operon. The modulation of the biofilm formation capacities of E. coli or those of other bacteria capable of being genetically manipulated may be of use both for reducing and for improving the impact of biofilms in a number of industrial and medical applications.


Phospholipase D activity regulates the binding of leukotriene B4 to human polymorphonuclear leukocytes.
Unsaturated fatty acids, such as arachidonic acid, have been implicated as second messengers of various cellular responses. In this paper, we demonstrate that the release of arachidonate from human polymorphonuclear leukocytes (PMNL) via a pathway initiated by phospholipase D (PLD) mediates phorbol myristate acetate (PMA)-induced desensitization of leukotriene B4 (LTB4) receptors. PMA caused a delayed release of arachidonic acid from PMNL, which occurred within minutes of the generation of the PLD products, phosphatidic acid and diglyceride, from [3H]lysophosphatidylcholine prelabeled PMNL. Moreover, stimulating PMNL with PMA in the presence of ethanol resulted in the formation of phosphatidylethanol at the expenses of phosphatidic acid, diglyceride and arachidonic acid. The PMA-induced generation of these three PLD products was inhibited by mepacrine which, in parallel, significantly blocked PMA-induced desensitization of [3H]LTB4 binding, which suggested that elevation of one or more of these products played a role in desensitization. In contrast, under basal conditions mepacrine reduced levels of these three lipids in a dose-related manner and, in parallel, increased basal [3H]LTB4 binding to PMNL. The reduction of PMA-induced LTB4 receptor desensitization by mepacrine could be overcome to various degrees by adding back PLD-derived lipids such as arachidonic acid. These data demonstrate that [3H]LTB4 binding to PMNL is decreased by PLD-derived lipids and suggests that intracellular arachidonic acid may modulate PMNL responsiveness to LTB4 activation.


Hypothesis: Paralog Formation from Progenitor Proteins and Paralog Mutagenesis Spur the Rapid Evolution of Telomere Binding Proteins.
Through elegant studies in fungal cells and complex organisms, we propose a unifying paradigm for the rapid evolution of telomere binding proteins (TBPs) that associate with either (or both) telomeric DNA and telomeric proteins. TBPs protect and regulate telomere structure and function. Four critical factors are involved. First, TBPs that commonly bind to telomeric DNA include the c-Myb binding proteins, OB-fold single-stranded binding proteins, and G-G base paired Hoogsteen structure (G4) binding proteins. Each contributes independently or, in some cases, cooperatively, to provide a minimum level of telomere function. As a result of these minimal requirements and the great abundance of homologs of these motifs in the proteome, DNA telomere-binding activity may be generated more easily than expected. Second, telomere dysfunction gives rise to genome instability, through the elevation of recombination rates, genome ploidy, and the frequency of gene mutations. The formation of paralogs that diverge from their progenitor proteins ultimately can form a high frequency of altered TBPs with altered functions. Third, TBPs that assemble into complexes (e.g., mammalian shelterin) derive benefits from the novel emergent functions. Fourth, a limiting factor in the evolution of TBP complexes is the formation of mutually compatible interaction surfaces amongst the TBPs. These factors may have different degrees of importance in the evolution of different phyla, illustrated by the apparently simpler telomeres in complex plants. Selective pressures that can utilize the mechanisms of paralog formation and mutagenesis to drive TBP evolution along routes dependent on the requisite physiologic changes.


High-resolution MR of the spinal cord in humans and rats.
Human and rat cervical spinal cords were imaged with high-resolution spin-echo and inversion-recovery pulse sequences in an experimental 1.9-T MR system. The gross morphology of the cord was easily discernible in fresh and fixed specimens, including the white and gray commissures, dorsal and ventral horns, and lateral and posterior funiculi. The T1, T2, and spin-density values for gray and white matter were determined from these images and were found to be 914 msec, 114 msec, and 71% for white matter other than the dorsal columns, and 946 msec, 87 msec, and 80% for gray matter in human spinal cords. These values are reduced considerably after formalin fixation: T1 to 56% (white matter) and 54% (gray matter) of prefixation values, T2 to 52% (white matter) and 70% (gray matter) of fresh values, and spin density to 90% (white matter) and 96% (gray matter) of prefixation values. Interestingly, the central gray matter demonstrates higher signal intensity than the white matter on both short and long TR/TE images. This intensity difference was observed for both human and rat spinal cords, before and after fixation, and can be explained by the relatively small T1 differences between gray matter and white matter and the gray matter-white matter spin-density ratios: 1.127 for fresh and 1.203 for fixed specimens.


Epidemiology and Sequence-Based Evolutionary Analysis of Circulating Non-Polio Enteroviruses.
Enteroviruses (EVs) are positive-sense RNA viruses, with over 50,000 nucleotide sequences publicly available. While most human infections are typically associated with mild respiratory symptoms, several different EV types have also been associated with severe human disease, especially acute flaccid paralysis (AFP), particularly with endemic members of the EV-B species and two pandemic types-EV-A71 and EV-D68-that appear to be responsible for recent widespread outbreaks. Here we review the recent literature on the prevalence, characteristics, and circulation dynamics of different enterovirus types and combine this with an analysis of the sequence coverage of different EV types in public databases (e.g., the Virus Pathogen Resource). This evaluation reveals temporal and geographic differences in EV circulation and sequence distribution, highlighting recent EV outbreaks and revealing gaps in sequence coverage. Phylogenetic analysis of the EV genus shows the relatedness of different EV types. Recombination analysis of the EV-A species provides evidence for recombination as a mechanism of genomic diversification. The absence of broadly protective vaccines and effective antivirals makes human enteroviruses important pathogens of public health concern.


Engaging stakeholders in research to address water-energy-food (WEF) nexus challenges.
The water-energy-food (WEF) nexus has become a popular, and potentially powerful, frame through which to analyse interactions and interdependencies between these three systems. Though the case for transdisciplinary research in this space has been made, the extent of stakeholder engagement in research remains limited with stakeholders most commonly incorporated in research as end-users. Yet, stakeholders interact with nexus issues in a variety of ways, consequently there is much that collaboration might offer to develop nexus research and enhance its application. This paper outlines four aspects of nexus research and considers the value and potential challenges for transdisciplinary research in each. We focus on assessing and visualising nexus systems; understanding governance and capacity building; the importance of scale; and the implications of future change. The paper then proceeds to describe a novel mixed-method study that deeply integrates stakeholder knowledge with insights from multiple disciplines. We argue that mixed-method research designs-in this case orientated around a number of cases studies-are best suited to understanding and addressing real-world nexus challenges, with their inevitable complex, non-linear system characteristics. Moreover, integrating multiple forms of knowledge in the manner described in this paper enables research to assess the potential for, and processes of, scaling-up innovations in the nexus space, to contribute insights to policy and decision making.


Anger Dimensions and Mental Health Following a Disaster: Distribution and Implications After a Major Bushfire.
Anger is an important dimension of affect and a prominent feature of posttraumatic mental health, but it is commonly overlooked in postdisaster settings. We aimed to examine the distribution and implications of significant anger problems in the aftermath of a natural disaster, via analyses of Beyond Bushfires survey data from 736 residents of rural communities 5 years after the 2009 Black Saturday bushfires in Victoria, Australia. Assessments included the five-item Dimensions of Anger Reaction (DAR-5) scale along with measures of PTSD, depression, and significant mental illness, and indicators of life satisfaction, suicidality, hostile aggressive behavior, and violence exposure. The results indicated that approximately 10% of respondents from areas highly affected by the bushfires scored above the provisional cutoff criteria for significant anger problems on the DAR-5, which was a more than 3-fold increase, OR = 3.26, relative to respondents from areas of low-to-moderate bushfire impact. The rates were higher among women, younger participants, and those who were unemployed, and co-occurred commonly, although not exclusively, with other postdisaster mental health problems. Anger problems were also associated with lower life satisfaction, β = -.31, an 8-fold increase in suicidal ideation, OR = 8.68, and a nearly 13-fold increase in hostile aggressive behavior, OR = 12.98. There were associations with anger problems and violence exposure, which were reduced when controlling for covariates, including probable PTSD. The findings provide evidence indicating that anger is a significant issue for postdisaster mental health and should be considered routinely alongside other posttraumatic mental health issues.


Rapid exclusion of acute myocardial infarction in patients with undetectable troponin using a high-sensitivity assay.
This paper sought to evaluate whether high sensitivity troponin (hs-cTnT) can immediately exclude acute myocardial infarction (AMI) at a novel 'rule out' cut-off. Subgroup analysis of recent evidence suggests that undetectable hs-cTnT may exclude AMI at presentation. In a cohort study, we prospectively enrolled patients with chest pain, evaluating them with standard troponin T and testing for hs-cTnT (Roche Diagnostics, Basel, Switzerland) at presentation. The primary outcome was a diagnosis of AMI. We also followed up patients for adverse events within 6 months. After subsequent clinical implementation of hs-cTnT, we again evaluated whether initially undetectable hs-cTnT ruled out a subsequent rise. Of 703 patients in the cohort study, 130 (18.5%) had AMI, none of whom initially had undetectable hs-cTnT (sensitivity: 100.0%, 95% confidence interval [CI]: 95.1% to 100.0%, negative predictive value: 100.0%, 95% CI: 98.1% to 100.0%). This strategy would rule out AMI in 27.7% of patients, 2 (1.0%) of whom died or had AMI within 6 months (1 periprocedural AMI, 1 noncardiac death). We evaluated this approach in an additional 915 patients in clinical practice. Only 1 patient (0.6%) with initially undetectable hs-cTnT had subsequent elevation (to 17 ng/l), giving a sensitivity of 99.8% (95% CI: 99.1% to 100.0%) and a negative predictive value of 99.4% (95% CI: 96.6% to 100.0%). Undetectable hs-cTnT at presentation has very high negative predictive value, which may be considered to rule out AMI, identifying patients at low risk of adverse events. Pending further validation, this strategy may reduce the need for serial testing and empirical treatment, enabling earlier reassurance for patients and fewer unnecessary evaluations and hospital admissions.


Decorin overexpression reduces atherosclerosis development in apolipoprotein E-deficient mice.
Atherosclerosis results from accumulation of macrophages and extracellular matrix in the arterial wall. Decorin, a small matrix proteoglycan, is able to regulate cell proliferation, migration and growth factors' activity. We investigated the effect of decorin overexpression on atherosclerosis progression in apolipoprotein E-deficient (ApoE(-/-)) mice. Female ApoE(-/-) mice, 10 weeks old (early treatment, n = 20) and 20 weeks old (delayed treatment, n = 20) were administered intravenously with either an adenovirus (2.5 x 10(9) plaque-forming units/mouse) containing human decorin gene (Ad-Dcn) or beta-galactosidase (LacZ), or PBS. Transgenic decorin was mainly expressed in the liver, and was secreted in the plasma up to 4 weeks. Six weeks after treatment, no significant difference in aortic root lesion size was observed between LacZ- and PBS-control groups. In contrast, Ad-Dcn-treated mice showed significantly reduced atherosclerotic lesions as compared to controls in both early and delayed treatment groups (2.9 +/- 1.1% versus 5.5 +/- 0.4%; p = 0.004 and 13.4 +/- 1.3% versus 19.9 +/- 1.41%; p = 0.009, respectively). In parallel, macrophage, gelatinase activity and collagen plaque content were also reduced. Interestingly, plasma triglycerides were reduced and decorin formed complexes with transforming growth factor-beta1 (TGF-beta1) that resulted in reduced circulating free-TGF-beta1. In conclusion, systemic overexpression of decorin reduces inflammation, triglycerides and fibrosis in atherosclerotic plaques of ApoE(-/-) mice resulting in slowing down of disease progression.


Involvement of Heme Oxygenase-1 Participates in Anti-Inflammatory and Analgesic Effects of Aqueous Extract of Hibiscus taiwanensis.
Anti-inflammatory effects of the aqueous extract of Hibiscus taiwanensis (AHT) were used in lipopolysaccharide (LPS-)stimulated mouse macrophage RAW264.7 cells and carrageenan (Carr-)induced mouse paw edema model. When RAW264.7 macrophages were treated with AHT together with LPS, a concentration-dependent inhibition of nitric oxide (NO), tumor necrosis factor (TNF-α), and prostaglandin E2 (PGE(2)) levels productions were detected. Western blotting revealed that AHT blocked protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and elevated heme oxygenase-1 (HO-1), significantly. In the animal test, AHT decreased the paw edema at the 4th and the 5th h after Carr administration, and it increased the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in the paw tissue. We also demonstrated AHT decreased the NO, TNF-α, and PGE2 levels on the serum level at the 5th h after the Carr injection. Western blotting revealed that AHT decreased Carr-induced iNOS, and COX-2, and increased HO-1 expressions at the 5th h in the edema paw. These findings demonstrated that AHT has excellent anti-inflammatory activities in vitro and in vivo and thus it has great potential to be used as a source for natural health products.


2-methoxyoestradiol levels and placental catechol-O-methyltransferase expression in patients with late-onset preeclampsia.
Deficiencies in placental catechol-O-methyltransferase (COMT) and circulating 2-methoxyoestradiol (2-ME) have been shown to be related to early onset preeclampsia. The aim of this study was to investigate levels of 2-ME in the serum and urine of patients with late-onset preeclampsia and to compare those levels to those of normal pregnant women. In addition, we examined placental COMT expression in both groups. Fifteen patients with preeclampsia and 15 normal pregnant women were enrolled. 2-ME levels were evaluated by ELISA and placental COMT expression was examined by Western blot analysis. 2-ME levels in serum [median 181.1 pg/mL, interquartile range (IQR) 119.6-244.3 vs. 61.2 pg/mL, IQR 12.0-133.7, respectively, p = 0.004] and urine (median 143.3 pg/mL, IQR 35.0-328.2 vs. 0.5 pg/mL, IQR 0.4-4.6, respectively, p < 0.001) were significantly increased in patients with late-onset preeclampsia compared to those in normal pregnant women at term. There was no significant difference in placental COMT expression between the two groups. Increased levels of 2-ME in patients with late-onset preeclampsia might be a product of a compensatory mechanism in patients with late-onset preeclampsia.


Toward noninvasive quantification of brain radioligand binding by combining electronic health records and dynamic PET imaging data.
Quantitative analysis of positron emission tomography (PET) brain imaging data requires a metabolite-corrected arterial input function (AIF) for estimation of distribution volume and related outcome measures. Collecting arterial blood samples adds risk, cost, measurement error, and patient discomfort to PET studies. Minimally invasive AIF estimation is possible with simultaneous estimation (SIME), but at least one arterial blood sample is necessary. In this study, we describe a noninvasive SIME (nSIME) approach that utilizes a pharmacokinetic input function model and constraints derived from machine learning applied to an electronic health record database consisting of "long tail" data (digital records, paper charts, and handwritten notes) that were collected ancillary to the PET studies. We evaluated the performance of nSIME on 95 [(11)C]DASB PET scans that had measured AIFs. The results indicate that nSIME is a promising alternative to invasive AIF measurement. The general framework presented here may be expanded to other metabolized radioligands, potentially enabling quantitative analysis of PET studies without blood sampling. A glossary of technical abbreviations is provided at the end of this paper.


The standard isoform of CD44 is preferentially expressed in atypical papillomas and carcinomas of the choroid plexus.
Isoforms of the CD44 adhesion molecule have been assigned a pivotal role in tumor invasion and metastasis. CD44 splice variants may be selectively expressed in various normal and neoplastic tissues. We investigated immunohistochemically the presence of the standard (H) and two variant (v3, v6) isoforms of the CD44 molecule in a series comprising 13 choroid plexus papillomas (WHO grade I) and 8 carcinomas (WHO grade III). In the papilloma group, 5 tumors showed variable cellular pleomorphism and foci of infiltrative growth, and were tentatively classified as atypical papillomas. Autopsy specimens of normal pediatric and adult choroid plexus were used as control. Western-blot analysis of CD44H was carried out on 4 carcinomas, 1 papilloma and on normal choroid plexus. The proliferation rate was assessed by MIB-1 immunoreactivity. The normal choroid plexuses and 9 papillomas were negative for the standard as well as the variant CD44 molecules investigated. Four atypical papillomas and 5 carcinomas expressed CD44H. CD44v3 and CD44v6 were only detected in one of the atypical papillomas also positive for CD44H. These data indicate that CD44H is preferentially expressed on atypical papillomas and carcinomas and may correlate with the infiltrative growth of these tumors.


Temperature shift experiments with an ftsZ84(Ts) strain reveal rapid dynamics of FtsZ localization and indicate that the Z ring is required throughout septation and cannot reoccupy division sites once constriction has initiated.
FtsZ is an essential division protein in bacteria that functions by forming a ring at midcell that mediates septation. To further study the function of the Z ring the effect of a temperature-sensitive mutation, ftsZ84(Ts), on ring dynamics and septal progression was examined. Shifting a strain carrying an ftsZ84(Ts) mutation to the nonpermissive temperature led to loss of Z rings within 1 min. Septal ingrowth was immediately inhibited, and sharply demarcated septa, present at the time of the shift, were gradually replaced by blunted septa. These results indicate that the Z ring is required throughout septation. Shifting filaments to permissive temperature led to a rapid localization of FtsZ84 at regular intervals. Included in these localization events were complete and partial rings as well as spots, although some of these eventually aborted. These results reveal the rapid dynamics of FtsZ localization and indicate that nucleation sites are formed in the absence of FtsZ function. Interestingly, Z rings could not reform at division sites that were constricted although they could reform at sites that had not begun constriction.


Does the cellular bronchoalveolar lavage fluid profile reflect the severity of sarcoidosis?
The aim of this study was to assess whether the cellular bronchoalveolar lavage fluid (BALF) profile, particularly the number of polymorphonuclear neutrophils (PMNs), is associated with disease severity of sarcoidosis and its usefulness in determining remission. Twenty-six nonsmoking outpatients with sarcoidosis were included in this study. The patients were divided into two subgroups according to the absolute number of PMNs in BALF: < or =0.2x10(4) cells x mL(-1) (group 1; n = 15) and >0.2x10(4) cells x mL(-1) (group 2; n = 11). The radiographic stage, high-resolution computed tomography (HRCT) findings, 67Ga lung uptake as well as lung function tests differed significantly between group 1 and 2. Follow-up revealed that 14 (93.3%) patients of group 1 compared to four (36.4%) of group 2 recovered spontaneously without the help of corticosteroids. In contrast, no differences were found in the number of lymphocytes in BALF nor in the serum angiotensin converting enzyme (sACE) level between both groups. The number of PMNs, the transfer factor of the lungs for carbon monoxide (TL,CO), the forced expiratory volume in one second (FEV1) and one of the HRCT subscores discriminated between patients with different disease progression. Of these parameters the PMNs appeared to be the only one which differentiated patients who demonstrated remission and those who deteriorated. In conclusion, these results indicate that the number of polymorphonuclear neutrophils in bronchoalveolar lavage fluid distinguish between sarcoidosis patients who demonstrated remission and those having a more severe course of the disease. Whether polymorphonuclear neutrophils may be considered as markers of disease activity and/or prognosis in sarcoidosis needs further investigation.


Harnessing quantum transport by transient chaos.
Chaos has long been recognized to be generally advantageous from the perspective of control. In particular, the infinite number of unstable periodic orbits embedded in a chaotic set and the intrinsically sensitive dependence on initial conditions imply that a chaotic system can be controlled to a desirable state by using small perturbations. Investigation of chaos control, however, was largely limited to nonlinear dynamical systems in the classical realm. In this paper, we show that chaos may be used to modulate or harness quantum mechanical systems. To be concrete, we focus on quantum transport through nanostructures, a problem of considerable interest in nanoscience, where a key feature is conductance fluctuations. We articulate and demonstrate that chaos, more specifically transient chaos, can be effective in modulating the conductance-fluctuation patterns. Experimentally, this can be achieved by applying an external gate voltage in a device of suitable geometry to generate classically inaccessible potential barriers. Adjusting the gate voltage allows the characteristics of the dynamical invariant set responsible for transient chaos to be varied in a desirable manner which, in turn, can induce continuous changes in the statistical characteristics of the quantum conductance-fluctuation pattern. To understand the physical mechanism of our scheme, we develop a theory based on analyzing the spectrum of the generalized non-Hermitian Hamiltonian that includes the effect of leads, or electronic waveguides, as self-energy terms. As the escape rate of the underlying non-attracting chaotic set is increased, the imaginary part of the complex eigenenergy becomes increasingly large so that pointer states are more difficult to form, making smoother the conductance-fluctuation pattern.


Postdischarge Outcome Domains in Pediatric Critical Care and the Instruments Used to Evaluate Them: A Scoping Review.
Assessing outcomes after pediatric critical illness is imperative to evaluate practice and improve recovery of patients and their families. We conducted a scoping review of the literature to identify domains and instruments previously used to evaluate these outcomes. Scoping review. We queried PubMed, EMBASE, PsycINFO, Cumulative Index of Nursing and Allied Health Literature, and the Cochrane Central Register of Controlled Trials Registry for studies evaluating pediatric critical care survivors or their families published between 1970 and 2017. We identified articles using key words related to pediatric critical illness and outcome domains. We excluded articles if the majority of patients were greater than 18 years old or less than 1 month old, mortality was the sole outcome, or only instrument psychometrics or procedural outcomes were reported. We used dual review for article selection and data extraction and categorized outcomes by domain (overall health, emotional, physical, cognitive, health-related quality of life, social, family). Manuscripts evaluating outcomes after pediatric critical illness. None. Of 60,349 citations, 407 articles met inclusion criteria; 87% were published after 2000. Study designs included observational (85%), interventional (7%), qualitative (5%), and mixed methods (3%). Populations most frequently evaluated were traumatic brain injury (n = 96), general pediatric critical illness (n = 87), and congenital heart disease (n = 72). Family members were evaluated in 74 studies (18%). Studies used a median of 2 instruments (interquartile range 1-4 instruments) and evaluated a median of 2 domains (interquartile range 2-3 domains). Social (n = 223), cognitive (n = 183), and overall health (n = 161) domains were most frequently studied. Across studies, 366 unique instruments were used, most frequently the Wechsler and Glasgow Outcome Scales. Individual domains were evaluated using a median of 77 instruments (interquartile range 39-87 instruments). A comprehensive, generalizable understanding of outcomes after pediatric critical illness is limited by heterogeneity in methodology, populations, domains, and instruments. Developing assessment standards may improve understanding of postdischarge outcomes and support development of interventions after pediatric critical illness.


Diagnostic difficulty arising from rectal recovery in ulcerative colitis.
To ascertain whether the dogma that a normal rectal biopsy precludes a diagnosis of ulcerative colitis is correct. Rectal biopsy specimens from a prospective group of 24 asymptomatic patients, with an established diagnosis of ulcerative colitis, were examined in a blinded study alongside 10 normal rectal biopsy specimens from an age and sex matched patient cohort without ulcerative colitis. Each biopsy specimen was assessed by three pathologists and ascribed to one of four categories: normal; borderline abnormality (one or more minor nonspecific abnormalities which, when combined, did not fulfil the minimal acceptable criteria for a diagnosis of ulcerative colitis); minimal features of chronic ulcerative colitis; and unequivocal ulcerative colitis. Two patients with ulcerative colitis had normal biopsy specimens; nine specimens were categorised as borderline abnormality, one as showing the minimal changes of chronic ulcerative colitis, and 12 as having the typical changes of chronic ulcerative colitis. Thus, 11 (46%) of the 24 patients had a rectal biopsy specimen that was devoid of the acceptable attributes on which a diagnosis is established, despite a confident previous diagnosis. Ten of these 11 cases had disease limited to the rectum. Review of all previous histological biopsy specimens (n = 164) and clinical data, including drug treatment, failed to identify any attributes that might be prognostic markers for future rectal mucosal healing. A normal rectal biopsy specimen, though uncommon, may occur in longstanding colitis. Moreover, in 46% of these asymptomatic but established cases the degree of healing may preclude a diagnosis of ulcerative colitis without comprehensive clinical and radiological details. Pathologists need to be aware of this minimal end of the spectrum of disease.


Length mutations in human mitochondrial DNA.
By high-resolution, restriction mapping of mitochondrial DNAs purified from 112 human individuals, we have identified 14 length variants caused by small additions and deletions (from about 6 to 14 base pairs in length). Three of the 14 length differences are due to mutations at two locations within the D loop, whereas the remaining 11 occur at seven sites that are probably within other noncoding sequences and at junctions between coding sequences. In five of the nine regions of length polymorphism, there is a sequence of five cytosines in a row, this sequence being comparatively rare in coding DNA. Phylogenetic analysis indicates that, in most of the polymorphic regions, a given length mutation has arisen several times independently in different human lineages. The average rate at which length mutations have been arising and surviving in the human species is estimated to be many times higher for noncoding mtDNA than for noncoding nuclear DNA. The mystery of why vertebrate mtDNA is more prone than nuclear DNA to evolve by point mutation is now compounded by the discovery of a similar bias toward rapid evolution by length mutation.


Expression Patterns and Identified Protein-Protein Interactions Suggest That Cassava CBL-CIPK Signal Networks Function in Responses to Abiotic Stresses.
Cassava is an energy crop that is tolerant of multiple abiotic stresses. It has been reported that the interaction between Calcineurin B-like (CBL) protein and CBL-interacting protein kinase (CIPK) is implicated in plant development and responses to various stresses. However, little is known about their functions in cassava. Herein, 8 CBL (MeCBL) and 26 CIPK (MeCIPK) genes were isolated from cassava by genome searching and cloning of cDNA sequences of Arabidopsis CBLs and CIPKs. Reverse-transcriptase polymerase chain reaction (RT-PCR) analysis showed that the expression levels of MeCBL and MeCIPK genes were different in different tissues throughout the life cycle. The expression patterns of 7 CBL and 26 CIPK genes in response to NaCl, PEG, heat and cold stresses were analyzed by quantitative real-time PCR (qRT-PCR), and it was found that the expression of each was induced by multiple stimuli. Furthermore, we found that many pairs of CBLs and CIPKs could interact with each other via investigating the interactions between 8 CBL and 25 CIPK proteins using a yeast two-hybrid system. Yeast cells co-transformed with cassava MeCIPK24, MeCBL10, and Na+/H+ antiporter MeSOS1 genes exhibited higher salt tolerance compared to those with one or two genes. These results suggest that the cassava CBL-CIPK signal network might play key roles in response to abiotic stresses.


Dynamics of the cerebral blood flow response to step changes in end-tidal PCO2 and PO2 in humans.
This study examined the dynamics of the cerebral blood flow response to hypoxia and hypercapnia in humans. Middle cerebral artery blood flow (MCAF) was assessed continuously using transcranial Doppler ultrasound. MCAF was calculated on a beat-by-beat basis as the product of the intensity-weighted mean velocity and the total power of the reflected signal. End-tidal PCO2 (PETCO2) and PO2 (PETO2) were controlled using a dynamic end-tidal forcing system. Six repeats of each of four protocols were administered to six subjects. The first was a control protocol with PETO2 held at 100 Torr and PETCO2 held 1-2 Torr above eucapnia throughout. The second was a hypoxic step protocol with PETO2 lowered from control values to 50 Torr for 20 min. The third was a hypercapnic step protocol with PETCO2 elevated from control by 7.5 Torr for 20 min. The fourth was a hypoxic-and-hypercapnic step protocol lasting 20 min. The total power of the Doppler signal remained relatively constant, suggesting that the cross-sectional area of the vessel changed little. After the initial transient in MCAF at the onset of the stimulus, no adaptation or progressive increase was observed over the remaining 20 min. A simple model consisting of a single pure delay, gain terms, time constants, and offsets for the on and off transients was fitted to the hypoxic and hypercapnic protocols. For hypercapnia, all the parameters for the onset were significantly different from the relief of the stimulus. The asymmetry was characterized by a slower on transient than off transient and also by a degree of undershoot after the relief of hypercapnia. Finally, the results from this study show that the cerebral blood flow response to hypoxia and hypercapnia in humans is much faster than has previously been thought.


Older people, the natural environment and common mental disorders: cross-sectional results from the Cognitive Function and Ageing Study.
To explore the hypothesis that higher exposure to natural environments in local areas is associated with a lower odds of depression and anxiety in later life. A cross-sectional study based on the year-10 interview of the Medical Research Council Cognitive Function and Ageing Study (CFAS), a population-based study of ageing in the UK. Postcodes of the CFAS participants were mapped onto small geographic units, lower-layer super output areas (LSOAs) and linked to environmental data from government databases. The natural environment was characterised as the percentage of green space and private gardens in each LSOA based on the UK Generalised Land Use 2001 Dataset. 2424 people aged 74 and over in the CFAS year-10 follow-up interview (2001) from 4 English centres (Cambridgeshire, Nottingham, Newcastle and Oxford). Depression and anxiety; clinical and subthreshold cases were identified using the Geriatric Mental State Examination (GMS) package and its associated diagnostic algorithm: the Automated Geriatric Examination for Computer Assisted Taxonomy. Compared with the lowest quartile, living in the highest quartile of neighbourhood natural environment provision was associated with a reduced odds of subthreshold depression (OR 0.66, 95% CI 0.46 to 0.95), anxiety symptoms (OR 0.62, 95% CI 0.46 to 0.83) and their co-occurrence (OR 0.55, 95% CI 0.35 to 0.84) after adjusting for individual-level factors. Controlling for area deprivation attenuated the strength of associations for subthreshold depression by 20% but not for anxiety symptoms or for co-occurrence of the conditions. A high exposure to natural environments (green space and gardens) in communities was associated with fewer mental disorders among older people. Increasing provision of green environments in local areas could be a potential population-level intervention to improve mental health among older people.


Brain mitochondrial function in a murine model of cerebral malaria and the therapeutic effects of rhEPO.
Cerebral malaria (CM) is a life-threatening complication of Plasmodium falciparum infection. The pathogenesis of CM is complex. Cerebral metabolic dysfunction is implicated in CM, which may be caused by both an impaired cerebral microcirculation and a dysregulated inflammatory response affecting cellular respiration of mitochondria. Recombinant human erythropoietin (rhEPO) is a promising new therapy that has been shown to reduce mortality in a mouse model of CM. In order to further elucidate the metabolic dysfunction in CM the objective of the present study was to assess brain mitochondrial respiratory function in CM with and without rhEPO treatment. The P. berghei ANKA - C57BL/6 murine model of CM was used. Mitochondrial respiration was analyzed in brain homogenates using high-resolution respirometry and a multiple substrate and inhibitor protocol. The animals were divided into four groups; infected injected with saline or with rhEPO, non-infected injected with saline or with rhEPO. Infected mice developed CM and treatment with rhEPO attenuated clinical signs of disease. There were no differences in respiratory parameters of brain mitochondria between infected and non-infected mice and no connection between disease severity and mitochondrial respiratory function. Treatment with rhEPO similarly had no effect on respiratory function. Thus cerebral metabolic dysfunction in CM does not seem to be directly linked to altered mitochondrial respiratory capacity as analyzed in brain homogenates ex vivo. This article is part of a Directed Issue entitled: Bioenergetic dysfunction, adaptation and therapy.


Risk of venous thromboembolic disease associated with hormonal contraceptives and hormone replacement therapy: a clinical review.
Venous thromboembolic events (VTEs) represent a serious complication related to hormonal contraception and hormone replacement therapy (HRT). Evidence on hormonal contraceptive- and HRT-related VTEs is derived almost exclusively from observational studies and points to a 2- to 6-fold increased relative risk of VTEs with either therapy. Oral contraceptive pills that contain third-generation progestins (desogestrel or gestodene) seem to be associated with greater VTE risk than those that contain levonorgestrel. Oral contraceptive pill use and HRT are associated with exponentially higher VTE relative risks when used by women who carry an inherited hypercoagulable state. The indication of a lower or a lack of VTE risk associated with the use of progestin-only contraceptives and with transdermal HRT suggests that these therapies may be safer than combination oral contraceptive pills and oral HRT for women in whom oral estrogen therapy is considered contraindicated. Data that support such safety advantages are limited and should be interpreted with caution.


Instrumental variables and interactions in the causal analysis of a complex clinical trial.
We consider the application of instrumental variable techniques in a longitudinal clinical trial in paediatric HIV/AIDS, with a substantial degree of non-compliance to randomized treatment (Nelfinavir versus placebo) and with left censoring of the outcome variable (HIV RNA concentration). We consider in detail the assumptions and implications behind the inclusion and exclusion of interactions between randomized arm and baseline covariates in modelling actual treatment received, and between treatment and baseline covariates in modelling outcome. Estimated treatment effects were sensitive to inclusion of interactions, and we show how such sensitivity can be explored and explained.


Effects of Combined Power Band Resistance Training on Sprint Speed, Agility, Vertical Jump Height, and Strength in Collegiate Soccer Players.
Soccer involves explosive physical actions requiring strength, power, and agility for optimal performance. Such attributes may be trained several ways, of which power-band resistance training has received limited attention regarding the potential for performance improvement in soccer players. This study serves to determine the effect of power-band resistance training on 1-repetition maximal (1RM) strength, speed, standing vertical jump (SVJ) height, and agility of collegiate soccer players. Seventeen male players (age: 20.47 ± 1.85 years, height: 1.77 ± 0.08 m, mass: 70.49 ± 4.15 kg) were matched and randomly allocated into either a conventional resistance group (CON, n = 8), or a power-band resistance training group (EXP, n = 9). Following a 6-week intervention, participants were re-assessed relative to their baseline values, showing improvements in 1RM squat mass (CON: +31.57%; EXP: +34.61%), 1RM deadlift mass (CON: +15.44%; EXP: +13.72%), and SVJ height (CON: +4.15%; EXP: +6.35%). Power-band resistance training produced greater results compared to conventional training in 1RM squat mass, even when between-group baseline values were controlled for (ANCOVA, F(1,14)=5.32, p = 0.037, η p 2 = .28 ). No other between-group differences were evident, showing no clear methodological superiority. Power-band resistance training shows potential as an effective training methodology compared to conventional resistance training to improve performance variables in university soccer players.


Expanding conceptualizations of harm reduction: results from a qualitative community-based participatory research study with people who inject drugs.
The perspectives of people who use drugs are critical in understanding why people choose to reduce harm in relation to drug use, what practices are considered or preferred in conceptualizations of harm reduction, and which environmental factors interfere with or support the use of harm reduction strategies. This study explores how people who inject drugs (PWID) think about harm reduction and considers the critical imperative of equity in health and social services delivery for this community. This community-based participatory research study was conducted in a Canadian urban centre. Using a peer-based recruitment and interviewing strategy, semi-structured qualitative interviews were conducted by and with PWID. The Vidaview Life Story Board, an innovative tool where interviewers and participant co-construct a visual "life-scape" using a board, markers, and customized picture magnets, was used to facilitate the interviews. The topics explored included injection drug use and harm reduction histories, facilitators and barriers to using harm reduction strategies, and suggestions for improving services and supports. Twenty-three interviews with PWID (14 men and 9 women) were analysed, with a median age of 50. Results highlighted an expanded conceptualization of harm reduction from the perspectives of PWID, including motivations for adopting harm reduction strategies and a description of harm reduction practices that went beyond conventional health-focused concerns. The most common personal practices that PWID used included working toward moderation, employing various cognitive strategies, and engaging in community activities. The importance of social or peer support and improving self-efficacy was also evident. Further, there was a call for less rigid eligibility criteria and procedures in health and social services, and the need to more adequately address the stigmatization of drug users. These findings demonstrated that PWID incorporate many personal harm reduction practices in their daily lives to improve their well-being, and these practices highlight the importance of agency, self-care, and community building. Health and social services are needed to better support these practices because the many socio-structural barriers this community faces often interfere with harm reduction efforts. Finally, "one size does not fit all" when it comes to harm reduction, and more personalized or de-medicalized conceptualizations are recommended.


Inhalation rewarming from hypothermia: an evaluation in -20 degrees C simulated field conditions.
The present study evaluates the efficacy of inhaling warm moist air as a method of rewarming from hypothermia in -20 degrees C field conditions. The method of inhalation rewarming is compared to two other methods of rewarming: a) passive rewarming; and b) passive rewarming, with a respiratory heat exchanger designed to minimize respiratory heat loss. Eight male subjects were rendered hypothermic by immersion in 15 degrees C water for 1 h. They were withdrawn from the tank earlier, in the event that their rectal temperature (Tre) decreased to 35 degrees C, or by 1.5 degrees C from the pre-immersion value. Upon completion of the immersion, they were placed in a well-insulated sleeping bag assembly and transferred to a cold room maintained at -20 degrees C for a 2 h rewarming period. They participated in 3 trials: Control-passive rewarming; Heat Treat-inhalation rewarming with the Heat Treat; HME-passive rewarming in conjunction with a respiratory heat and moisture exchanger (HME). During the rewarming period, inspired air temperature was -19.4 +/- 1.1 degrees C in the control trial. In the HME and Heat Treat trials subjects breathed via an oro-nasal mask. The inspired air temperature was +20.5 +/- 1.2 degrees C in the HME and +36.2 +/- 2.9 degrees C in the Heat Treat trial. The post-immersion drop in Tre was significant in all conditions. The reduction in the post-exposure drop in Tre observed with the Heat Treat may be attributed to the minimization of respiratory heat loss, since the magnitude of the reduction was similar to that observed with the HME.(ABSTRACT TRUNCATED AT 250 WORDS)


Psychosocial interventions for self-harm in adults.
Self-harm (SH; intentional self-poisoning or self-injury) is common, often repeated, and associated with suicide. This is an update of a broader Cochrane review first published in 1998, previously updated in 1999, and now split into three separate reviews. This review focuses on psychosocial interventions in adults who engage in self-harm. To assess the effects of specific psychosocial treatments versus treatment as usual, enhanced usual care or other forms of psychological therapy, in adults following SH. The Cochrane Depression, Anxiety and Neurosis Group (CCDAN) trials coordinator searched the CCDAN Clinical Trials Register (to 29 April 2015). This register includes relevant randomised controlled trials (RCTs) from: the Cochrane Library (all years), MEDLINE (1950 to date), EMBASE (1974 to date), and PsycINFO (1967 to date). We included RCTs comparing psychosocial treatments with treatment as usual (TAU), enhanced usual care (EUC) or alternative treatments in adults with a recent (within six months) episode of SH resulting in presentation to clinical services. We used Cochrane's standard methodological procedures. We included 55 trials, with a total of 17,699 participants. Eighteen trials investigated cognitive-behavioural-based psychotherapy (CBT-based psychotherapy; comprising cognitive-behavioural, problem-solving therapy or both). Nine investigated interventions for multiple repetition of SH/probable personality disorder, comprising emotion-regulation group-based psychotherapy, mentalisation, and dialectical behaviour therapy (DBT). Four investigated case management, and 11 examined remote contact interventions (postcards, emergency cards, telephone contact). Most other interventions were evaluated in only single small trials of moderate to very low quality.There was a significant treatment effect for CBT-based psychotherapy compared to TAU at final follow-up in terms of fewer participants repeating SH (odds ratio (OR) 0.70, 95% confidence interval (CI) 0.55 to 0.88; number of studies k = 17; N = 2665; GRADE: low quality evidence), but with no reduction in frequency of SH (mean difference (MD) -0.21, 95% CI -0.68 to 0.26; k = 6; N = 594; GRADE: low quality).For interventions typically delivered to individuals with a history of multiple episodes of SH/probable personality disorder, group-based emotion-regulation psychotherapy and mentalisation were associated with significantly reduced repetition when compared to TAU: group-based emotion-regulation psychotherapy (OR 0.34, 95% CI 0.13 to 0.88; k = 2; N = 83; GRADE: low quality), mentalisation (OR 0.35, 95% CI 0.17 to 0.73; k = 1; N = 134; GRADE: moderate quality). Compared with TAU, dialectical behaviour therapy (DBT) showed a significant reduction in frequency of SH at final follow-up (MD -18.82, 95% CI -36.68 to -0.95; k = 3; N = 292; GRADE: low quality) but not in the proportion of individuals repeating SH (OR 0.57, 95% CI 0.21 to 1.59, k = 3; N = 247; GRADE: low quality). Compared with an alternative form of psychological therapy, DBT-oriented therapy was also associated with a significant treatment effect for repetition of SH at final follow-up (OR 0.05, 95% CI 0.00 to 0.49; k = 1; N = 24; GRADE: low quality). However, neither DBT vs 'treatment by expert' (OR 1.18, 95% CI 0.35 to 3.95; k = 1; N = 97; GRADE: very low quality) nor prolonged exposure DBT vs standard exposure DBT (OR 0.67, 95% CI 0.08 to 5.68; k = 1; N =18; GRADE: low quality) were associated with a significant reduction in repetition of SH.Case management was not associated with a significant reduction in repetition of SH at post intervention compared to either TAU or enhanced usual care (OR 0.78, 95% CI 0.47 to 1.30; k = 4; N = 1608; GRADE: moderate quality). Continuity of care by the same therapist vs a different therapist was also not associated with a significant treatment effect for repetition (OR 0.28, 95% CI 0.07 to 1.10; k = 1; N = 136; GRADE: very low quality). None of the following remote contact interventions were associated with fewer participants repeating SH compared with TAU: adherence enhancement (OR 0.57, 95% CI 0.32 to 1.02; k = 1; N = 391; GRADE: low quality), mixed multimodal interventions (comprising psychological therapy and remote contact-based interventions) (OR 0.98, 95% CI 0.68 to 1.43; k = 1 study; N = 684; GRADE: low quality), including a culturally adapted form of this intervention (OR 0.83, 95% CI 0.44 to 1.55; k = 1; N = 167; GRADE: low quality), postcards (OR 0.87, 95% CI 0.62 to 1.23; k = 4; N = 3277; GRADE: very low quality), emergency cards (OR 0.82, 95% CI 0.31 to 2.14; k = 2; N = 1039; GRADE: low quality), general practitioner's letter (OR 1.15, 95% CI 0.93 to 1.44; k = 1; N = 1932; GRADE: moderate quality), telephone contact (OR 0.74, 95% CI 0.42 to 1.32; k = 3; N = 840; GRADE: very low quality), and mobile telephone-based psychological therapy (OR not estimable due to zero cell counts; GRADE: low quality).None of the following mixed interventions were associated with reduced repetition of SH compared to either alternative forms of psychological therapy: interpersonal problem-solving skills training, behaviour therapy, home-based problem-solving therapy, long-term psychotherapy; or to TAU: provision of information and support, treatment for alcohol misuse, intensive inpatient and community treatment, general hospital admission, or intensive outpatient treatment.We had only limited evidence on whether the intervention had different effects in men and women. Data on adverse effects, other than planned outcomes relating to suicidal behaviour, were not reported. CBT-based psychological therapy can result in fewer individuals repeating SH; however, the quality of this evidence, assessed using GRADE criteria, ranged between moderate and low. Dialectical behaviour therapy for people with multiple episodes of SH/probable personality disorder may lead to a reduction in frequency of SH, but this finding is based on low quality evidence. Case management and remote contact interventions did not appear to have any benefits in terms of reducing repetition of SH. Other therapeutic approaches were mostly evaluated in single trials of moderate to very low quality such that the evidence relating to these interventions is inconclusive.