Copper(II) sequentially loads onto the N-terminal amino group of the cellular prion protein before the individual octarepeats.
The cellular prion protein (PrPC) binds to Cu2+ ions in vivo, and a misfolded form of PrPC is responsible for a range of transmissible spongiform encephalopathies. Recently, disruption of Cu2+ homeostasis in mice has been shown to impart resistance to scrapie infection. Using full-length PrPC and model peptide fragments, we monitor the sequential loading of Cu2+ ions onto PrPC using visible circular dichroism. We show the N-terminal amino group of PrPC is not the principal binding site for Cu2+; however, surprisingly, it has an affinity for Cu2+ tighter than that of the individual octarepeat binding sites present within PrPC. We re-evaluate what is understood about the sequential loading of Cu2+ onto the full-length protein and show for the first time that Cu2+ loads onto the N-terminal amino group before the single octarepeat binding sites.


DNA methylation and RNA expression profiles in lung adenocarcinomas of never-smokers.
Lung cancer occurs in never-smokers. Epigenetic changes in lung cancer potentially represent important diagnostic, prognostic, and therapeutic targets. We compared DNA methylation profiles of 28 adenocarcinomas of the lungs of never-smokers with paired adjacent nonmalignant lung tissue. We correlated differential methylation changes with gene expression changes from the same 28 sample pairs. Using principal component analysis, we observed a distinct separation in methylation profiles between tumor and adjacent nonmalignant lung tissue. Tumors were generally hypomethylated compared with adjacent nonmalignant tissue. Of 1,906 CpG sites differentially methylated between tumor and nonmalignant tissue, 1,198 were within classically defined CpG islands where tumors were hypermethylated compared with nonmalignant tissue. A total of 708 sites were outside CpG islands where tumors were hypomethylated compared with nonmalignant tissue. There were significant differences in expression of 351 genes (23%) of the 1,522 genes matched to the differentially methylated CpG sites. Genes that were not significantly differentially expressed and were hypermethylated within CpG sites were enriched for homeobox genes. These results suggest that the methylation profiles of lung adenocarcinomas of never-smokers and adjacent nonmalignant lung tissue are significantly different. Despite the differential methylation of homeobox genes, no significant changes in expression of these genes were detected.


Characterization of a monoclonal antibody specific for Brucella smooth lipopolysaccharide and development of a competitive enzyme-linked immunosorbent assay to improve the serological diagnosis of brucellosis.
The reactivity of monoclonal antibody (MAb) 12G12 was analyzed in regard to the main biovars of Brucella species and some members of the families Enterobacteriaceae and Vibrionaceae which present serological cross-reactions with the smooth lipopolysaccharide (S-LPS) of Brucella species. This MAb was strictly directed against the common specific epitope of the Brucella S-LPS. It recognized all of the smooth Brucella strains and biovars except B. suis biovar 2. In order to improve the specificity of the serological diagnosis of brucellosis, a competitive enzyme-linked immunosorbent assay (cELISA) was developed with the horseradish peroxidase-conjugated MAbs 12G12 and S-LPS of B. melitensis Rev1. The specificity of the cELISA was analyzed with 936 serum samples from healthy cattle. The assay was evaluated with sera from heifers (n = 18) experimentally infected with B. abortus 544. After infection, the performance of the cELISA was in agreement with those of the complement fixation test and the rose Bengal plate test. Finally, the specificity of the assay was also evaluated in regard to false-positive serological reactions by using sera from heifers experimentally infected with Yersinia enterocolitica 0:9 (n = 4) and with field sera presenting false-positive reactions (n = 74). The specificity of the cELISA was greater than the specificities of the complement fixation test and the rose Bengal plate test. Indeed, the new assay detected only 31 of the 101 false-positive serum samples detected by at least one serological test.


Reductions in the mitochondrial DNA diversity of coral reef fish provide evidence of population bottlenecks resulting from Holocene sea-level change.
This study investigated the influence of reproductive strategy (benthic or pelagic eggs) and habitat preferences (lagoon or outer slope) on both diversity and genetic differentiation using a set of populations of seven coral reef fish species over different geographic scales within French Polynesia. We hypothesized that a Holocene sea-level decrease contributed to severe reduction of population size for species inhabiting lagoons and a subsequent decrease of genetic diversity. Conversely, we proposed that species inhabiting stable environments, such as the outer slope, should demonstrate higher genetic diversity but also more structured populations because they have potentially reached a migration-genetic drift equilibrium. Sequences of the 5' end of the mitochondrial DNA (mtDNA) control region were compared among populations sampled in five isolated islands within two archipelagos of French Polynesia. For all the species, no significant divergences among populations were found. Significant differences in mtDNA diversity between lagoonal and outer-slope species were demonstrated both for haplotype diversity and sequence divergence but none were found between species with different egg types. Pairwise mismatch distributions suggested rapid population growth for all the seven species involved in this study, but they revealed different distributions, depending on the habitat preference of the species. Although several scenarios can explain the observed patterns, the hypothesis of population size reduction events relative to Holocene sea-level regression and its consequence on French Polynesia coral reefs is the most parsimonious. Outer-slope species have undergone a probable weak and/or old bottleneck (outer reefs persisted during low sea level, leading to reef area reductions), whereas lagoonal species suffered a strong and/or recent bottleneck since Holocene sea-level regression resulted in the drying out of all the atolls that are maximum 70 meters deep. Since present sea level was reached between 5000 and 6000 years ago, different demographic events (bottlenecks or founder events) have lead to the actual populations of lagoons in French Polynesia.


Differences between pathological and physiological cardiac hypertrophy: novel therapeutic strategies to treat heart failure.
1. In general, cardiac hypertrophy (an increase in heart mass) is a poor prognostic sign. Cardiac enlargement is a characteristic of most forms of heart failure. Cardiac hypertrophy that occurs in athletes (physiological hypertrophy) is a notable exception. 2. Physiological cardiac hypertrophy in response to exercise training differs in its structural and molecular profile to pathological hypertrophy associated with pressure or volume overload in disease. Physiological hypertrophy is characterized by normal organization of cardiac structure and normal or enhanced cardiac function, whereas pathological hypertrophy is commonly associated with upregulation of fetal genes, fibrosis, cardiac dysfunction and increased mortality. 3. It is now clear that several signalling molecules play unique roles in the regulation of pathological and physiological cardiac hypertrophy. 4. The present review discusses the possibility of targeting cardioprotective signalling pathways and genes activated in the athlete's heart to treat or prevent heart failure.


Interrelation between viral and cellular DNA synthesis in mouse cells infected with the parvovirus minute virus of mice.
Mouse fibroblasts arrested in G0 by isoleucine deprivation were inoculated with the autonomous parvovirus minute virus of mice (MVM). Infected cells were released from the G0 block by transfer to complete medium and their progression to and and through the S phase was monitored. The onset of viral and cellular DNA synthesis coincided, suggesting that cellular factor(s) required for MVM DNA replication became available as soon as cells entered the S phase. Cellular DNA synthesis was reduced to about 60% by MVM infection. However, this inhibition did not decrease significantly the overall rate of DNA replication in infected cells because it was compensated by concomitant viral DNA synthesis. MVM infection delayed the movement of the cells out of S phase by at least 5 h. At any time post-infection, more than 95% of both viral and cellular DNA synthesis was sensitive to inhibition by aphidicolin. Since this drug is highly specific for cellular DNA polymerase alpha, the data are consistent with a major role of this enzyme in the in vivo DNA replication of autonomous parvovirus. The assembly of 95% of virus progeny particles was concomitant with a late phase or viral DNA replication which accounted for 30% of the total viral DNA synthesized. The inhibition of this residual viral DNA replication by aphidicolin reduced dramatically the size of the burst of infectious particles; this observation concurs with other evidence to suggest that encapsidation is driven by a late replication event sensitive to this drug.


The utility of Coccidioides antigen and antibody detection in cerebrospinal fluid in the diagnosis of canine central nervous system coccidioidomycosis.
To evaluate the utility of enzyme immunoassays (EIAs) for the detection of Coccidioides antigen and antibody in CSF in the diagnosis of CNS coccidioidomycosis in dogs. 51 dogs evaluated for CNS disease in a single specialty center in Tucson in 2016. Excess CSF after routine analysis was banked after collection from dogs presented to the neurology service. Samples were tested by EIA for presence of Coccidioides antigen and antibody. Clinical data were collected from medical records retrospectively. 22 dogs were diagnosed with CNS coccidioidomycosis (CCM) or another neurologic disease (non-CCM). These groups of dogs overlapped in the presenting complaints, MRI results, and routine CSF analysis results. Four dogs, all with CCM, had positive antigen EIA results. With clinical diagnosis used as the reference standard, CSF antigen testing had low sensitivity (20%) but high specificity (100%) for diagnosis of CCM. Ten dogs with CCM and 4 dogs with other diagnoses had antibody detected in CSF by EIA. Sensitivity of CSF antibody testing was 46%, specificity was 86%, and positive and negative predictive values for the study population were 71% and 68%, respectively. Diagnosis of CNS coccidioidomycosis in dogs in an endemic region was hampered by overlap of clinical signs with other neurologic disorders and the low sensitivity of confirmatory diagnostics. The evaluated Coccidioides-specific EIAs performed on CSF can aid in the diagnosis. A prospective study is warranted to corroborate and refine these preliminary findings.


Role of the Bed Nucleus of the Stria Terminalis in PTSD: Insights From Preclinical Models.
Post-traumatic stress disorder (PTSD) afflicts approximately 8% of the United States population and represents a significant public health burden, but the underlying neural mechanisms of this and other anxiety- and stressor-related disorders are largely unknown. Within the last few decades, several preclinical models of PSTD have been developed to help elucidate the mechanisms underlying dysregulated fear states. One brain area that has emerged as a critical mediator of stress-related behavioral processing in both clinical and laboratory settings is the bed nucleus of the stria terminalis (BNST). The BNST is interconnected with essential emotional processing regions, including prefrontal cortex, hippocampus and amygdala. It is activated by stressor exposure and undergoes neurochemical and morphological alterations as a result of stressor exposure. Stress-related neuro-peptides including corticotropin-releasing factor (CRF) and pituitary adenylate cyclase activating peptide (PACAP) are also abundant in the BNST, further implicating an involvement of BNST in stress responses. Behaviorally, the BNST is critical for acquisition and expression of fear and is well positioned to regulate fear relapse after periods of extinction. Here, we consider the role of the BNST in stress and memory processes in the context of preclinical models of PTSD.


Association Between Renal Function, Diastolic Dysfunction, and Postoperative Atrial Fibrillation Following Cardiac Surgery.
Background: Renal dysfunction is associated with a higher rate of atrial fibrillation in clinical practice. This study investigated the associations between renal function, left ventricular (LV) diastolic dysfunction, and postoperative atrial fibrillation (POAF). Methods and Results: A total of 265 consecutive patients who underwent cardiac surgery were prospectively enrolled in the study. Echocardiography was performed before cardiac surgery. The patients were divided into 3 groups based on estimated glomerular filtration rate (eGFR) (group 1, ≥90ml·min-1·1.73m-2; group 2, 60-90ml·min-1·1.73m-2; and group 3, <60ml·min-1·1.73m-2). POAF occurred in 83 of 265 patients (31.3%). The rate of new-onset POAF increased from 15.2% (12/79) in group 1 to 27.8% (27/97) in group 2 and 49.4% (44/89) in group 3 (P<0.001). Further, with increasing renal dysfunction from groups 1 to 3, the rate of LV diastolic dysfunction - defined as E/e' >15 - also increased (group 1, 19.0%; group 2, 38.1%; and group 3, 48.3%; P<0.001). Absolute eGFR was significantly correlated with E/e' ratio (r=-0.39, P<0.001). Renal function remained as the independent predictor of POAF on multivariate analysis (odds ratio, 1.90; 95% confidence interval: 1.26-2.87; P=0.002). Conclusions: In patients undergoing cardiac surgery, decreased eGFR was associated with an increased rate of LV diastolic dysfunction with a subsequent increase in the rate of POAF.


Point process analyses of variations in smoking rate by setting, mood, gender, and dependence.
The immediate emotional and situational antecedents of ad-libitum smoking are still not well understood. We reanalyzed data from ecological momentary assessment using novel point process analyses to assess how craving, mood, and social setting influence smoking rate, as well as to assess the moderating effects of gender and nicotine dependence. Smokers (N = 304) recorded craving, mood, and social setting using electronic diaries when smoking and at random nonsmoking times over 16 days of smoking. Point process analysis, which makes use of the known random sampling scheme for momentary variables, examined main effects of setting and interactions with gender and dependence. Increased craving was associated with higher rates of smoking, particularly among women. Negative affect was not associated with smoking rate, even in interaction with arousal, but restlessness was associated with substantially higher smoking rates. Women's smoking tended to be less affected by negative affect. Nicotine dependence had little moderating effect on situational influences. Smoking rates were higher when smokers were alone or with others who were smoking, and smoking restrictions reduced smoking rates. However, the presence of others who are smoking undermined the effects of restrictions. The more sensitive point process analyses confirmed earlier findings, including the surprising conclusion that negative affect by itself was not related to smoking rates. Contrary to hypothesis, men's and not women's smoking was influenced by negative affect. Both smoking restrictions and the presence of others who are not smoking suppress smoking, but the presence of others who are not smoking undermines the effects of restrictions. Point process analyses of ecological momentary assessment data can bring out even small influences on smoking rate.


Modeling Measurement as a Sequential Process: Autoregressive Confirmatory Factor Analysis (AR-CFA).
To model data from multi-item scales, many researchers default to a confirmatory factor analysis (CFA) approach that restricts cross-loadings and residual correlations to zero. This often leads to problems of measurement-model misfit while also ignoring theoretically relevant alternatives. Existing research mostly offers solutions by relaxing assumptions about cross-loadings and allowing residual correlations. However, such approaches are critiqued as being weak on theory and/or indicative of problematic measurement scales. We offer a theoretically-grounded alternative to modeling survey data called an autoregressive confirmatory factor analysis (AR-CFA), which is motivated by recognizing that responding to survey items is a sequential process that may create temporal dependencies among scale items. We compare an AR-CFA to other common approaches using a sample of 8,569 people measured along five common personality factors, showing how the AR-CFA can improve model fit and offer evidence of increased construct validity. We then introduce methods for testing AR-CFA hypotheses, including cross-level moderation effects using latent interactions among stable factors and time-varying residuals. We recommend considering the AR-CFA as a useful complement to other existing approaches and treat AR-CFA limitations.


A description of an automatic continuous equilibrium system for the measurement of dissolved gaseous mercury.
A novel continuous equilibrium system with high time resolution, i.e. every ten minutes, was developed to sample and determine dissolved gaseous mercury (DGM) in natural surface waters. The system is based on the opposite flow principle, can be connected to a ship's bow water system, and can be applied under most ambient conditions, such as high wind speeds and onboard a moving ship. For the DGM determination the system uses the measured equilibrium concentration of mercury established between the aqueous and gaseous phases, i.e. DGM = Hg(extr)/k(H'), where Hg(extr) is the measured mercury concentration in the outgoing gas phase and k(H') is the dimensionless Henry's Law constant at the desired temperature and salinity. The efficiency of the system was investigated via theoretical calculations and by comparing the continuous equilibrium system with discrete samples. The measurements obtained by the continuous equilibrium system agree within 13% at the 95% confidence level with the measurements of discrete samples obtained by the traditional technique. The theoretical calculations estimated that the continuous equilibrium system described here had an efficiency of 99% for determining the DGM concentration.


Prediction of Zn2(V, Nb, Ta)N3 Monolayers for Optoelectronic Applications.
A new family of ternary nitride materials, Zn2(V, Nb, Ta)N3 monolayers, is predicted. A fabrication mechanism of the Zn2(V, Nb, Ta)N3 monolayers is proposed based on the chemical vapor deposition approach used for their bulk counterparts. The calculations show that these monolayers are thermodynamically and environmentally stable and that the Zn2VN3 monolayer is the most stable and the easiest to synthesize. The Zn2VN3 monolayer also has the highest strength and elasticity. The Zn2(V, Nb, Ta)N3 monolayers are semiconductors with nearly equal direct and indirect band gaps. Considering optoelectronic properties, the predicted monolayers are transparent to the visible light and provide shielding in the ultraviolet region. Thus, the predicted Zn2(V, Nb, Ta)N3 monolayers are promising for applications in LED devices and as blocking layers in tandem solar cells.


In for a penny, in for a pound: examining motivated memory through the lens of retrieved context models.
When people encounter items that they believe will help them gain reward, they later remember them better than others. A recent model of emotional memory, the emotional context maintenance and retrieval model (eCMR), predicts that these effects would be stronger when stimuli that predict high and low reward can compete with each other during both encoding and retrieval. We tested this prediction in two experiments. Participants were promised £1 for remembering some pictures, but only a few pence for remembering others. Their recall of the content of the pictures they saw was tested after 1 min and, in experiment 2, also after 24 h. Memory at the immediate test showed effects of list composition. Recall of stimuli that predicted high reward was greater than of stimuli that predicted lower reward, but only when high- and low-reward items were studied and recalled together, not when they were studied and recalled separately. More high-reward items in mixed lists were forgotten over a 24-h retention interval compared with items studied in other conditions, but reward did not modulate the forgetting rate, a null effect that should be replicated in a larger sample. These results confirm eCMR's predictions, although further research is required to compare that model against alternatives.


High-frequency click-evoked otoacoustic emissions and behavioral thresholds in humans.
Relationships between click-evoked otoacoustic emissions (CEOAEs) and behavioral thresholds have not been explored above 5 kHz due to limitations in CEOAE measurement procedures. New techniques were used to measure behavioral thresholds and CEOAEs up to 16 kHz. A long cylindrical tube of 8 mm diameter, serving as a reflectionless termination, was used to calibrate audiometric stimuli and design a wideband CEOAE stimulus. A second click was presented 15 dB above a probe click level that varied over a 44 dB range, and a nonlinear residual procedure extracted a CEOAE from these click responses. In some subjects (age 14-29 years) with normal hearing up to 8 kHz, CEOAE spectral energy and latency were measured up to 16 kHz. Audiometric thresholds were measured using an adaptive yes-no procedure. Comparison of CEOAE and behavioral thresholds suggested a clinical potential of using CEOAEs to screen for high-frequency hearing loss. CEOAE latencies determined from the peak of averaged, filtered temporal envelopes decreased to 1 ms with increasing frequency up to 16 kHz. Individual CEOAE envelopes included both compressively growing longer-delay components consistent with a coherent-reflection source and linearly or expansively growing shorter-delay components consistent with a distortion source. Envelope delays of both components were approximately invariant with level.


Interrater agreement and stability of the Functional Independence Measure for Children (WeeFIM): use in children with developmental disabilities.
Examination of the interrater agreement and stability of ratings obtained using the Functional Independence Measure for Children (WeeFIM) in a sample of children with developmental disabilities. A relational design was used in which two sets of WeeFIM scores were collected under four conditions: same rater-short interval; same rater-long interval; different rater-short interval; and different rater-long interval. WeeFIM scores were collected in outpatient developmental rehabilitation centers, school programs, and the children's homes. Data were collected for 205 children ranging in age from 11 to 87 months. All children had a medical diagnosis of disability and were receiving habilitative-educational intervention or follow-along services including neurodevelopmental surveillance. The WeeFIM instrument examines basic daily living and functional skills in children from birth to 7 years of age. The WeeFIM is modeled after the Functional Independence Measure (FIM) for adults and includes 18 items in the following subscales: self-care, sphincter control, transfers, locomotion, communication, and social cognition. Kappa values for items ranged from .44 to .82. Intraclass correlation coefficients (ICC) for the six subscales ranged from .73 to .98. Total WeeFIM ICC values were greater than .95 for all analyses. The WeeFIM ratings for the 205 children with developmental disabilities participating in this investigation were consistent across raters and time.


[Management of abnormal uterine bleeding].
Bleeding disorders are one of the most frequent gynecological problems. The causes of bleeding disorders, and their frequency in particular, vary depending on the age of the woman affected. In premenopause and perimenopause, the most frequent causes are hormonal, in up to 90 % of cases, as well as organic changes in the uterus such as myomas, adenomyosis uteri, or endometrial polyps, in up to 70 % of cases. Coagulation defects cause increased bleeding, particularly in girls and young women, with no other recognizable cause. The treatment of bleeding disorders is causally based, although if the woman does not wish to have children, the therapeutic algorithm in many cases leads to similar symptomatic measures. The following therapeutic approaches, listed in order of increasing efficacy, are mainly used in the treatment of increased bleeding: gestagen, estrogen-gestagen combination, levonorgestrel (Mirena) and endometrial ablation or myoma enucleation, with comparable success rates, and finally hysterectomy. Embolization of the uterine artery in myomas or adenomyosis uteri, nonsteroidal anti-inflammatory drugs, and antifibrinolytic agents represent alternatives that may be useful in individual cases. The paper provides an overview of the various causes, useful diagnostic measures, and treatment options in uterine bleeding disorders.


Calculated vibrational states of ozone up to dissociation.
A new accurate global potential energy surface for the ground electronic state of ozone [R. Dawes et al., J. Chem. Phys. 139, 201103 (2013)] was published fairly recently. The topography near dissociation differs significantly from previous surfaces, without spurious submerged reefs and corresponding van der Waals wells. This has enabled significantly improved descriptions of scattering processes, capturing the negative temperature dependence and large kinetic isotope effects in exchange reaction rates. The exchange reactivity was found to depend on the character of near-threshold resonances and their overlap with reactant and product wavefunctions, which in turn are sensitive to the potential. Here we present global "three-well" calculations of all bound vibrational states of three isotopic combinations of ozone ((48)O3, (16)O2 (18)O, (16)O2 (17)O) for J = 0 and J = 1 with a focus on the character and density of highly excited states and discuss their impact on the ozone isotopic anomaly. The calculations were done using a parallel symmetry-adapted Lanczos method with the RV3 code. Some comparisons were made with results obtained with the improved relaxation method implemented in the Heidelberg multi-configuration time-dependent Hartree code.


Oral pregabalin as an add-on treatment for status epilepticus.
Oral antiepileptic drugs (AEDs) represent possible add-on options in refractory status epilepticus (SE). In this setting, pregabalin (PGB) has not been reported before. Over the last 42 months, we identified 11 SE episodes (10 patients) treated with PGB in our hospital. Its use was prompted by the favorable pharmacokinetic profile, devoid of drug-drug interactions. The patients mostly had refractory, partial SE. Only two patients were managed in the intensive care unit (ICU). We found a definite electroclinical response in 5 of 11, already evident 24 h after PGB introduction, and a possible response (concomitantly with other AEDs) in 3 of 11 of the episodes; 3/11 did not respond. The treatment was well tolerated. Partial SE appeared to better respond than generalized convulsive SE. PGB appears to be an interesting option as add-on treatment in refractory partial SE.


Synthesis of superconducting nanocables of FeSe encapsulated in carbonaceous shell.
The recent discovery of superconductivity in iron selenide has attracted considerable attention due to the simplicity of composition, unconventional nature of superconductivity, and ease of synthesis. We have synthesized superconducting FeSe nanowires with a simple catalyst-aided vapor transport reaction at 800 °C in an inert atmosphere. The precursors were chosen to be elemental Se and iron acetylacetonate [Fe(III)(C₅H₈O₂)₃]. These vaporized very easily, thereby facilitating transport, and also contributed to the formation of a carbonaceous shell encapsulating the FeSe nanowires. The superconductivity of these nanocables was confirmed through magnetic measurements and a T(c) of ≈8 K was obtained for an ensemble of nanocables. The length of FeSe filling inside the carbon nanofibers could be varied by controlling the reaction conditions while the diameter of nanowires was dependent on the thickness of Au-Pd coating used as a catalyst. Extensive analysis through high-resolution microscopy revealed that there was considerable lattice contraction of FeSe in the nanocable up to about 3.6% along the c-direction leading to a reduced spacing between the (001) lattice planes. Interestingly, this compression was more pronounced near the catalyst-FeSe interface and was reduced further along the length of the nanocable. The presence of carbon nanofibers as a shell around the FeSe protected the FeSe nanowires from both atmospheric O₂ and moisture attack, as was evident from the very long ambient condition shelf life of these nanocables, and also makes them more stable under e-beam irradiation.


Fabrication and structure analysis of poly(lactide-co-glycolic acid)/silk fibroin hybrid scaffold for wound dressing applications.
Silk fibroin (SF) and poly(lactide-co-glycolic acid) (PLGA) have been proved to be invaluable polymers in the field wound healing. This study aims at optimizing the electrospinning process of those polymers to make a hybrid membrane as a chronic wounds dressing. After characterizing the scaffolds, PLGA/SF (2:1), and PLGA scaffolds were selected for further study according to their superior tensile mechanical properties. The attachment and proliferation of mouse fibroblasts (L929) on scaffolds were measured using colorimetric assay and scanning electron microscopy. Furthermore, to evaluate the wound healing effect of the scaffolds in comparison with gauze and Comfeel(®) dressings, an excision wound model was conducted on diabetic rats. On the postoperative days of 3, 6, 9, 12, and 15, residual wound area was calculated using macroscopic data. In vitro results showed that the attachment and proliferation of L929 were significantly increased on PLGA/SF (2:1) hybrid scaffold. Animal study and histopathological evaluation outcomes confirmed the in vitro results as well. On day 15, the residual wound area in PLGA/SF (2:1) hybrid membrane group was significantly smaller than PLGA and control groups. This promising scaffold has the potential to be used for the upcoming development of wound dressings with or without biological drugs.


Predicting major bleeding in patients with noncardioembolic stroke on antiplatelets: S2TOP-BLEED.
To develop and externally validate a prediction model for major bleeding in patients with a TIA or ischemic stroke on antiplatelet agents. We combined individual patient data from 6 randomized clinical trials (CAPRIE, ESPS-2, MATCH, CHARISMA, ESPRIT, and PRoFESS) investigating antiplatelet therapy after TIA or ischemic stroke. Cox regression analyses stratified by trial were performed to study the association between predictors and major bleeding. A risk prediction model was derived and validated in the PERFORM trial. Performance was assessed with the c statistic and calibration plots. Major bleeding occurred in 1,530 of the 43,112 patients during 94,833 person-years of follow-up. The observed 3-year risk of major bleeding was 4.6% (95% confidence interval [CI] 4.4%-4.9%). Predictors were male sex, smoking, type of antiplatelet agents (aspirin-clopidogrel), outcome on modified Rankin Scale ≥3, prior stroke, high blood pressure, lower body mass index, elderly, Asian ethnicity, and diabetes (S2TOP-BLEED). The S2TOP-BLEED score had a c statistic of 0.63 (95% CI 0.60-0.64) and showed good calibration in the development data. Major bleeding risk ranged from 2% in patients aged 45-54 years without additional risk factors to more than 10% in patients aged 75-84 years with multiple risk factors. In external validation, the model had a c statistic of 0.61 (95% CI 0.59-0.63) and slightly underestimated major bleeding risk. The S2TOP-BLEED score can be used to estimate 3-year major bleeding risk in patients with a TIA or ischemic stroke who use antiplatelet agents, based on readily available characteristics. The discriminatory performance may be improved by identifying stronger predictors of major bleeding.


An attachment perspective on therapeutic processes and outcomes.
Over the past decade, there has been an explosion of interest in clinical applications of attachment theory. In the present article, we briefly describe John Bowlby's model of therapeutic change, the therapeutic relationship, and the therapist's role in emotional healing. We then review empirical evidence for three key propositions in Bowlby's model. First, a client's sense of security during therapy is crucial for facilitating therapeutic work. Second, a therapist's own sense of security contributes to positive therapeutic outcomes. Third, attachment insecurities can be effectively reduced in therapy, and movement toward greater attachment security is central to achieving favorable therapeutic outcomes. In sum, research evidence confirms the importance of establishing what Bowlby called a safe haven and a secure base within a therapeutic relationship.


Molecular typing of a Legionella pneumophila outbreak in Ontario, Canada.
An outbreak of Legionnaires' disease at a long-term care facility in Ontario, Canada from September to October 2005 resulted in the death of 23 residents and the illness of 112 other people. In response, molecular methods were developed to detect Legionella pneumophila in clinical lung samples and to subtype isolates from clinical and environmental samples. The targeted genetic loci included Legionella-specific virulence determinants (mip, icmO, sidA and lidA) and core bacterial determinants (ftsZ, trpS and dnaX). An established amplified fragment length polymorphism typing method provided the first indication of genetic relatedness between strains recovered from clinical samples and strains cultured from environmental samples taken from the outbreak site. These associations were verified using the European Working Group for Legionella Infections sequence-based typing protocol targeting the flaA, pilE, asd, mip, mompS and proA loci. These molecular typing methods confirmed the outbreak source as a contaminated air conditioning cooling tower.


Temporal dynamics of microparticle elevation following subarachnoid hemorrhage.
Microparticles (MPs), small membrane fragments shed from various cell types, have been implicated in thrombosis, inflammation, and endothelial dysfunction. Their involvement in subarachnoid hemorrhage (SAH) and the development of cerebral infarction and clinical deterioration caused by delayed cerebral ischemia (DCI) remain ill defined. The authors sought to quantify the magnitude of elevations in MPs, delineate the temporal dynamics of elevation, and analyze the correlation between MPs and DCI in patients with SAH. On the day of hemorrhage and on Days 1, 3, 5, 7, and 10 after hemorrhage, peripheral blood samples were drawn from 22 patients with SAH. Plasma samples were labeled with Annexin V and CD142, CD41a, CD235a, CD146, CD66b, or von Willebrand factor (vWF) and were quantified by flow cytometry. Clinical data, including the 3-month extended Glasgow Outcome Scale (GOS-E) scores, infarction as measured on MRI at 14 days after SAH, and vasospasm as measured by transcranial Doppler ultrasonography and angiography, were collected and compared with the MP burden. When averaged over time, all MP subtypes were elevated relative to controls. The CD235a+(erythrocyte)-, CD66b+(neutrophil)-, and vWF-associated MPs peaked on the day of hemorrhage and quickly declined. The CD142+(tissue factor [TF])-associated MPs and CD146+(endothelial cell)-associated MPs were significantly elevated throughout the study period. There was a strong negative correlation between TF-expressing and endothelial-derived MPs at Day 1 after SAH and the risk of infarction at Day 14 after SAH. Microparticles of various subtypes are elevated following SAH; however, the temporal profile of this elevation varies by subtype. Those subtypes closely associated with thrombosis and endothelial dysfunction, for example, CD145+(TF)-associated MPs and CD146+(endothelial cell)-associated MPs, had the most durable response and demonstrated a significant negative correlation with radiographic infarction at 14 days after SAH. Levels of these MPs predict infarction as early as Day 1 post-SAH.


Body-image and eating disturbances predict onset of depression among female adolescents: a longitudinal study.
This study examined data from a 4-year school-based longitudinal study (n = 1,124), to test whether the increase in major depression that occurs among girls during adolescence may be partially explained by the body-image and eating disturbances that emerge after puberty. Elevated body dissatisfaction, dietary restraint, and bulimic symptoms at study entry predicted onset of subsequent depression among initially nondepressed youth in bivariate analyses controlling for initial depressive symptoms. Although the unique effect for body dissatisfaction was not significant in the multivariate model, this set of risk factors was able to fairly accurately foretell which girls would go on to develop major depression. Results were consistent with the assertion that the body-image- and eating-related risk factors that emerge after puberty might contribute to the elevated rates of depression for adolescent girls.


Comparison of the Outcomes of Complex Orbital Fracture Repair with and without a Surgical Navigation System: A Prospective Cohort Study with Historical Controls.
In severe orbital fractures, restoration of orbital shape and volume is required to avoid diplopia and posttraumatic enophthalmos. The purpose of this study was to compare outcomes between navigation-aided and conventional techniques for complex unilateral orbital fractures using titanium mesh. The outcomes and the computed tomography-measured orbital volume of two groups of orbital complex unilateral reconstruction cases were compared. The study group consisted of a consecutive cohort of unilateral severe orbital fracture that underwent surgery with the aid of a Brainlab navigation system. A historical control group was composed of consecutive operations performed immediately before the beginning of navigation system use. A total of 55 operations were then identified and studied for patient characteristics, diplopia and globe position, preoperative and postoperative orbital volumes, complications, need for revision surgery, and the surgeon's performance. Postoperative diplopia severity was lower in the study group than in the control group. Orbital volume analysis showed that reconstructed orbital volume in the study group was closer to unaffected orbital volume compared with the control group. Significant orbital volume reduction in the reconstructed orbit could be achieved in the study group, and there was no significant reduction in the control group compared with the unaffected side. The globe projection was higher compared with the preoperative situation in the study group than in the control group. The navigational platform could also contribute to reduce the learning curve. This study demonstrated that computer-assisted techniques improve outcomes compared with conventional techniques. Therapeutic, III.


Cerebrospinal fluid glutamate levels in chronic migraine.
Both preclinical and clinical data link glutamate to the migraine pathophisiology. Altered plasma, platelets and cerebrospinal (CSF) glutamate levels have been reported in migraine patients. Chronic migraine is comorbid with several conditions. It has been recently shown chronic migraine comorbidity with fibromyalgia. The objective of this study was to study cerebrospinal fluid glutamate levels in chronic migraine patients with and without fibromyalgia. We studied 20 chronic migraine patients, with and without fibromyalgia, compared to age-sex matched controls. CSF glutamate levels were measured by HPLC. CSF glutamate demonstrated significantly higher levels in patients with fibromyalgia compared to those without fibromyalgia. Patients overall had higher CSF glutamate levels than controls. Mean pain score correlated with glutamate levels in chronic migraine patients. Tender points, the hallmark of fibromyalgia, can be considered as pressure allodynia, and is probably mediated by central sensitization, with increase in CSF glutamate levels. We postulate chronic migraine patients with fibromyalgia, in addition to have more disabling headaches, suffer from a more severe central sensitization process. This subtype of patients may respond to medications modulating glutamate receptors. Headache intensity correlate with glutamate levels in chronic migraine patients.


Medical examination for asbestos-related disease.
There are millions of workers whose exposure to asbestos dust prior to the implementation of asbestos regulation and improved control measures places them at risk of asbestos-related disease today. In addition, workers are still being exposed to significant amounts of asbestos, when asbestos materials in place are disturbed during renovation, repair, or demolition. Given the continued presence of asbestos-containing materials in industrial, commercial, and residential settings throughout the U.S., a sizeable population remains at risk of asbestos-related disease. This article reviews the health effects associated with exposure to asbestos and delineates the steps necessary for the comprehensive screening and clinical assessment for asbestos-related disease, in order to assist physicians in identifying and preventing illness associated with exposure to asbestos among their patients.


Use of the canonical discriminant analysis to select SNP markers for bovine breed assignment and traceability purposes.
Several market research studies have shown that consumers are primarily concerned with the provenance of the food they eat. Among the available identification methods, only DNA-based techniques appear able to completely prevent frauds. In this study, a new method to discriminate among different bovine breeds and assign new individuals to groups was developed. Bulls of three cattle breeds farmed in Italy - Holstein, Brown, and Simmental - were genotyped using the 50K SNP Illumina BeadChip. Multivariate canonical discriminant analysis was used to discriminate among breeds, and discriminant analysis (DA) was used to assign new observations. This method was able to completely identify the three groups at chromosome level. Moreover, a genome-wide analysis developed using 340 linearly independent SNPs yielded a significant separation among groups. Using the reduced set of markers, the DA was able to assign 30 independent individuals to the proper breed. Finally, a set of 48 high discriminant SNPs was selected and used to develop a new run of the analysis. Again, the procedure was able to significantly identify the three breeds and to correctly assign new observations. These results suggest that an assay with the selected 48 SNP could be used to routinely track monobreed products.


Phytoestrogens in health and disease.
Phytoestrogens are compounds found in a wide variety of plant foods that historically are said to exhibit estrogen-like activity and, more recently, have been reported to display both estrogenic and anti-estrogenic effects. Population-based studies have been interpreted to suggest that consumption of a phytoestrogen-rich diet is protective against breast, prostate, and bowel cancer and cardiovascular disease and ameliorates estrogen-deficiency symptoms in postmenopausal women. Consequently, there is a global movement towards increased consumption of phytoestrogen-rich foods and tabletized concentrated isoflavone extracts are being heavily promoted. Evaluating the effects and hence the potential benefits and risks of phytoestrogens is a complex task. The interindividual diversity and complexity in dietary phytoestrogen absorption and metabolism make the bioactivity of these compounds unpredictable. Epidemiological studies of relationships between phytoestrogens and cancer and cardiovascular disease that take into account confounding factors are scarce. Results of many of the in vitro and in vivo studies are conflicting and confusing. These compounds do not simply mimic the effects of human steroidal estrogen but rather demonstrate both similar and divergent actions. The ultimate actions of these compounds in specific cells are determined by many factors, including the relative levels of estrogen receptor (ER) alpha and ER beta and the diverse cocktail of co-activators and co-repressors present in any given cell type. Therefore, effects vary according to the phytoestrogen studied, cell line, tissue, species, and response being evaluated. Overall, it is naive to assume that exposure to these compounds is always good; inappropriate or excessive exposure may be detrimental. Extensive documentation of the specific intracellular effects of the various phytoestrogens in different tissues, the relationships between timing and duration of exposure and disease, and results from prospective randomized studies in humans of their clinical effects and potential side effects are essential. Only then can widespread recommendations regarding the dietary and pharmacological intake of these compounds be made.


Dynamic selection for forage quality and quantity in response to phenology and insects in an Arctic ungulate.
Spatiotemporal variation in forage is a primary driver of ungulate behavior, yet little is known about the nutritional components they select, and how selection varies across the growing season with changes in forage quality and quantity. We addressed these uncertainties in barren-ground caribou (Rangifer tarandus), which experience their most important foraging opportunities during the short Arctic summer. Recent declines in Arctic caribou populations have raised concerns about the influence of climate change on summer foraging opportunities, given shifting vegetation conditions and insect harassment, and their potential effects on caribou body condition and demography. We examined Arctic caribou selection of summer forage by pairing locations from females in the Central Arctic Herd of Alaska with spatiotemporal predictions of biomass, digestible nitrogen (DN), and digestible energy (DE). We then assessed selection for these nutritional components across the growing season at landscape and patch scales, and determined whether foraging opportunities were constrained by insect harassment. During early summer, at the landscape scale, caribou selected for intermediate biomass and high DN and DE, following expectations of the forage maturation hypothesis. At the patch scale, however, caribou selected for high values of all forage components, particularly DN, suggesting that protein may be limiting. During late summer, after DN declined below the threshold for protein gain, caribou exhibited a switch at both spatial scales, selecting for higher biomass, likely enabling mass and fat deposition. Mosquito activity strongly altered caribou selection of forage and increased their movement rates, while oestrid fly activity had little influence. Our results demonstrate that early and late summer periods afford Arctic caribou distinct foraging opportunities, as they prioritize quality earlier in the summer and quantity later. Climate change may further constrain caribou access to DN as earlier, warmer Arctic summers may be associated with reduced DN and increased mosquito harassment.


"Benign" tumors and "early detection" in mammography-screened patients of a natural cohort with breast cancer.
Although the cure of breast cancer by "early detection" and prompt treatment rests on the belief that all breast cancers grow at the same rate, many cancers have been shown to grow rapidly and others slowly. In particular, mammography screening may often detect the slow-growing, nonaggressive tumors that might not be found until much later, if at all. We reviewed the medical records of a natural cohort of 233 patients. The cohort comprised all women who received their first antineoplastic treatment for breast cancer at Yale-New Haven Hospital during the period from January 1 through December 31, 1988, and had a median follow-up thereafter of 82.4 months. The mammography screen-detected group (MSDG) contained 97 (42%) of the 233 breast cancers. The rates of subsequent freedom from cancer deaths or recurrences were 95% (92 patients) in the MSDG and 79% (107 patients) in all other patients (log-rank 2P<.001). This superiority occurred partly because 90 (93%) of the MSDG were in the good prognosis TNM stages 0, I, and IIA, compared with 92 (68%) of the non-MSDG (chi2 2P = .001). Of the 31 patients with stage 0 (carcinoma in situ), all of whom had disease-free survival, 24 (77%) were found by mammography screening. Even within similar TNM stages, however, the MSDG had distinctly better disease-free survival results than the non-MSDG. For patients in TNM stages I and IIA, the "failure events" had respective rates of 2% and 13% (log-rank 2P = .02). The results suggest that many of the breast cancers found by mammography screening have excellent prognosis not just because of early detection, but also because many of the cancers are relatively benign, requiring minimal therapy.


Mast Cells Granular Contents Are Crucial for Deep Vein Thrombosis in Mice.
Deep vein thrombosis (DVT) and its complication pulmonary embolism have high morbidity reducing quality of life and leading to death. Cellular mechanisms of DVT initiation remain poorly understood. We sought to determine the role of mast cells (MCs) in DVT initiation and validate MCs as a potential target for DVT prevention. In a mouse model, DVT was induced by partial ligation (stenosis) of the inferior vena cava. We demonstrated that 2 strains of mice deficient for MCs were completely protected from DVT. Adoptive transfer of in vitro differentiated MCs restored thrombosis. MCs were present in the venous wall, and the number of granule-containing MCs decreased with thrombosis. Pharmacological depletion of MCs granules or prevention of MC degranulation also reduced DVT. Basal plasma levels of von Willebrand factor and recruitment of platelets to the inferior vena cava wall after DVT induction were reduced in MC-deficient mice. Stenosis application increased plasma levels of soluble P-selectin in wild-type but not in MC-deficient mice. MC releasate elevated ICAM-1 (intercellular adhesion molecule-1) expression on HUVEC (human umbilical vein endothelial cells) in vitro. Topical application of compound 48/80, an MC secretagogue, or histamine, a Weibel-Palade body secretagogue from MCs, potentiated DVT in wild-type mice, and histamine restored thrombosis in MC-deficient animals. MCs exacerbate DVT likely through endothelial activation and Weibel-Palade body release, which is, at least in part, mediated by histamine. Because MCs do not directly contribute to normal hemostasis, they can be considered potential targets for prevention of DVT in humans.


Comparing three generic musculoskeletal models to estimate the tibiofemoral reaction forces during gait and sit-to-stand tasks.
The choice of musculoskeletal (MSK) model is crucial for performing MSK estimations to evaluate muscle demands and joint forces. This study compared two previously published generic MSK models and a modified model to estimate tibiofemoral reaction forces (TFRF) during gait, sit-to-stand, and stand-to-sit. The estimated tibiofemoral reaction forces were compared with an in vivo dataset from six patients using an instrumented knee prosthesis. A correlation and root mean square error (RMSE) in the time-series analysis and relative peak error (RPE) were evaluated. The results showed that the three MSK models were similar in estimating the vertical forces, with a large correlation, and RPE was found around 20 % during gait. The RMSE and the RPE indicated that the modified model had lower total and lateral compartment forces errors for sit-to-stand and stand-to-sit, showing the best performance. The shear forces for all tasks and models showed significant errors. Future MSK studies should consider these findings when researching functional tasks. The modified model was found to be more effective in estimating the vertical tibiofemoral joint reaction forces in tasks that impose greater demands on muscle forces and require high knee and hip flexion.


Prenatal exposure to a low concentration of carbon monoxide disrupts hippocampal long-term potentiation in rat offspring.
The aim of the present study was to investigate whether functional changes at CA3-CA1 synapses in the hippocampus could underlie learning and memory deficits produced in rat offspring by a prenatal exposure model simulating the carbon monoxide (CO) exposure observed in human cigarette smokers. Electrophysiological endpoints, including long-term potentiation, were examined in 15- to 30-day-old male rats whose mothers were exposed, from day 0 to day 20 of gestation, to 150 ppm of CO resulting in blood levels of carboxyhemoglobin comparable to those found in human cigarette smokers. Evoked field excitatory postsynaptic potentials were measured in the stratum radiatum in hippocampal slices. Results show that before tetanus, input/output functions, presynaptic volley, and paired-pulse facilitation were not affected in CO-exposed offspring, indicating that basal synaptic excitability and terminal Ca(2+) influx were not influenced by prenatal exposure to this gas. Conversely, evoked field excitatory postsynaptic potentials potentiation in response to tetanization was reduced by about 23% and decayed rapidly to baseline values in slices from CO-exposed animals. No changes between and within groups were observed in paired-pulse facilitation after tetanus. The selective impairment of long-term potentiation expression exhibited by CO-exposed rats was paralleled by a significant decrease in heme-oxygenase 2 and neuronal nitric-oxide synthase in the hippocampus. No changes in either enzymatic activity were found in frontal cortex and cerebellum. These electrophysiological and biochemical alterations might account for cognitive deficits previously observed in rats exposed prenatally to CO. Our findings could have clinical implications for the offspring of mothers who smoke during pregnancy.


Polychlorinated biphenyls and DDT alter species composition in mixed cultures of algae.
Either DDT or polychlorinated biphenyls were added to mixed cultures containing a marine diatom and a marine green alga that were sensitive and resistant, respectively, to these organochlorine compounds. The diatom grew faster and was therefore dominant in control cultures, but its dominance diminished in treated cultures, even at concentrations of chlorinated hydrocarbons that had no apparent effect in pure cultures. Such stable pollutants could disrupt the species composition of phytoplankton communities, thereby affecting whole eco-systems.


Effective? Engaging? Secure? Applying the ORCHA-24 framework to evaluate apps for chronic insomnia disorder.
Mobile health offers many opportunities; however, the 'side-effects' of health apps are often unclear. With no guarantee health apps first do no harm, their role as a viable, safe and effective therapeutic option is limited. To assess the quality of apps for chronic insomnia disorder, available on the Android Google Play Store, and determine whether a novel approach to app assessment could identify high-quality and low-risk health apps in the absence of indicators such as National Health Service (NHS) approval. The Organisation for the Review of Care and Health Applications- 24 Question Assessment (ORCHA-24), 24 app assessment criteria concerning data privacy, clinical efficacy and user experience, answered on a 'yes' or 'no' and evidence-driven basis, was applied to assess 18 insomnia apps identified via the Android Google Play Store, in addition to the NHS-approved iOS app Sleepio. 63.2% of apps (12/19) provided a privacy policy, with seven (36.8%) stating no user data would be shared without explicit consent. 10.5% (2/19) stated they had been shown to be of benefit to those with insomnia, with cognitive behavioural therapy apps outperforming hypnosis and meditation apps (p=0.046). Both the number of app downloads (p=0.29) and user-review scores (p=0.23) were unrelated to ORCHA-24 scores. The NHS-approved app Sleepio, consistently outperformed non-accredited apps across all domains of the ORCHA-24. Apps for chronic insomnia disorder exhibit substantial variation in adherence to published data privacy, user experience and clinical efficacy standards, which are not clearly correlated with app downloads or user-review scores. In absence of formal app accreditation, the ORCHA-24 could feasibly be used to highlight the risk-benefit profiles of health apps prior to downloading.


Artificial airglow excited by high-power radio waves.
High-power electromagnetic waves beamed into the ionosphere from ground-based transmitters illuminate the night sky with enhanced airglow. The recent development of a new intensified, charge coupled-device imager made it possible to record optical emissions during ionospheric heating. Clouds of enhanced airglow are associated with large-scale plasma density cavities that are generated by the heater beam. Trapping and focusing of electromagnetic waves in these cavities produces accelerated electrons that collisionally excite oxygen atoms, which emit light at visible wavelengths. Convection of plasma across magnetic field lines is the primary source for horizontal motion of the cavities and the airglow enhancements. During ionospheric heating experiments, quasi-cyclic formation, convection, dissipation and reappearance of the cavites comprise a major source of long-term variability in plasma densities during ionospheric heating experiments.


Unsaturated fatty acid regulation of peroxisome proliferator-activated receptor alpha activity in rat primary hepatocytes.
Peroxisome proliferator-activated receptors (PPARs alpha, beta, gamma1, and gamma2) are widely regarded as monitors of intracellular nonesterified fatty acid (NEFA) levels. As such, fatty acid binding to PPAR leads to changes in the transcription of many genes involved in lipid metabolism and storage. Although the composition of the intracellular NEFA pool is likely an important factor controlling PPAR activity, little information is available on factors affecting its composition. Accordingly, we have examined the effects of exogenous fatty acids on PPARalpha activity and NEFA pool composition in rat primary hepatocytes. Prior to the addition of fatty acids to primary hepatocytes, nonesterified unsaturated fatty acid levels are very low, representing </=0.5% of the total fatty acid in the cell. The relative abundance of putative PPARalpha ligands in the NEFA pool is 20:4n-6 = 18:2n-6 = 18:1n-9 > 22:6n-3 > 18:3n-3/6 = 20:5n-3. Of these fatty acids, only 20:5n-3 and 22:6n-3 consistently induced PPARalpha activity. Metabolic labeling of primary hepatocytes indicated that both 14C-18:1n-9 and 14C-20:5n-3 are rapidly assimilated into neutral and polar lipids. Although the addition of 18:1n-9 had no effect on NEFA pool composition, 20:5n-3 mass increased >15-fold within 90 min. Changes in NEFA pool 20:5n-3 mass correlated with dynamic changes in the PPARalpha-regulated transcript mRNACYP4A. Metabolic labeling also indicated that a significant fraction of 14C-20:5n-3 was elongated to 22:5n-3. Cells treated with 22:5n-3 or 22:6n-3 led to a significant accumulation of 20:5n-3 in the NEFA pool through a process that requires peroxisomal beta-oxidation and fatty acyl CoA thioesterase activity. Further analyses suggest that 20:5n-3 and 22:6n-3, but not 22:5n-3, are active ligands for PPARalpha. These studies suggest that basal fatty acid levels in the NEFA pool coupled with rates of fatty acid esterification, elongation, desaturation, peroxisomal beta-oxidation, and fatty acyl thioestease activity are important determinants controlling NEFA pool composition and PPARalpha activity.


Association of serum uric acid levels with blood pressure and the incidence of hypertension in the middle-aged and elderly populations.
This study aimed to investigate the relationship between serum uric acid (SUA) levels and hypertension in the middle-aged and elderly populations. The cross-sectional analysis included 13 349 middle-aged and elderly general health checkup examinees without cardiovascular disease. The retrospective cohort analysis included 6659 normotensive participants (mean age: 64.6 years). Participants were divided into three groups based on their SBP/DBP levels: normal (<120/<80 mmHg), high normal (120-129/<80 mmHg), and elevated (130-139/80-89 mmHg), and were classified into three groups based on the results of 75 g oral glucose tolerance test: normoglycemia, prediabetes, and diabetes. SUA levels were significantly associated with SBP and DBP in this cross-sectional study. Over a mean 6.5-year follow-up period, 2038 participants developed hypertension. According to the SUA quartiles, the incidence of hypertension increased [26.1% in quartile (Q1) (≤4.1 mg/dl), 28.6% in Q2 (4.2-4.9 mg/dl), 32.6% in Q3 (5.0-5.8 mg/dl), 34.9% in Q4 (≥5.9 mg/dl); P for trend <0.001]. In multivariable analyses, SUA levels were positively associated with hypertension incidence only in the normal BP group [Q4 vs. Q1 odds ratio (OR): 1.64, 95% confidence intervals (CIs): 1.11-2.44; Q3 vs. Q1 OR: 1.69, 95% CI: 1.19-2.42] and in the normoglycemic group (Q4 vs. Q1 OR: 1.34, 95% CI: 1.02-1.76; Q3 vs. Q1 OR: 1.36, 95% CI: 1.07-1.74). In the middle-aged and elderly populations, normotensive or normoglycemic individuals with SUA levels at least 5 mg/dl may be potential targets for SUA management to prevent hypertension.


Gel vehicles are not inherently more irritating than creams.
It has been thought that topical gels are inherently more irritating than topical creams. Nevertheless, the irritancies of topical products are potentially quite variable, and a priori assumptions about relative irritancy of gels versus creams may not be accurate. To determine whether a metronidazole gel formulation is more or less irritating to the skin compared to metronidazole creams. A total of 32 normal, healthy volunteers were tested using irritancy patches with 0.75% metronidazole gel and cream, 1% metronidazole cream, and petrolatum (used as the "negative control"). Blinded observers evaluated the application sites for signs of irritancy. A numerical score was assigned to these irritancy patch sites each day for 21 days, or until significant irritation developed, and cumulative irritancy scores were calculated for the study period. A mixed model of variance analysis was performed. After 21 days of evaluation, analysis of the mean cumulative irritancy scores for each of the agents used showed there to be no statistical difference in irritancy potential between the metronidazole gel and the metronidazole creams. However, the 1% metronidazole cream was significantly more irritating than petrolatum. There was no significant difference in the cumulative irritancy potential of cream and gel preparations of metronidazole. The irritancy of topical formulations for treating rosacea should be considered on a case by case basis.


Hepatocyte growth factor (HGF) and the satellite cell response following muscle lengthening contractions in humans.
The time-courses of satellite cell (SC) activation and protein expression of hepatocyte growth factor (HGF), HGF activator (HGFA), HGFA inhibitor-1 (HAI-1), and HGFA inhibitor-2 (HAI-2) in human skeletal muscle, as well as serum HGF following a single bout of muscle lengthening contractions, were determined. Eight recreationally active participants were recruited for the study. Subjects performed 300 lengthening contractions involving the quadriceps femoris muscles of a single leg at a fixed velocity of 180 degrees/s. Percutaneous muscle biopsies were taken before (PRE) and at 4 h (T4), 24 h (T24), 72 h (T72), and 120 h (T120) following the exercise. The protocol resulted in an increase in the number of SCs [neural cell adhesion molecule (NCAM)-labeled cells] expressed relative to total myonuclei, at T24, compared with both PRE and T4 (P<0.05), and peaked at T72 (approximately 80% increase vs. PRE, P<0.05). HGF protein increased significantly in serum from baseline (PRE) to T4 (P<0.05). Active HGF protein was detected in skeletal muscle at rest [14.4+/-1.3 average integrated density value (IDV)/actin average IDV] and tended to increase at early time-points (P=0.12). HGFA protein increased significantly from PRE to T24 (P<0.05). HAI-1 protein increased significantly from PRE to T24 (P<0.05). HAI-2 (32 kDa) increased significantly from baseline (PRE) by T24 (P<0.05), and also by T72 and T120 (P<0.05). We conclude that a single bout of lengthening muscle contractions is sufficient to activate SCs, which may involve both a local and systemic HGF response to contraction-induced injury.


Pyocin-resistant lipopolysaccharide mutans of Neisseria gonorrhoeae: alterations in sensitivity to normal human serum and polymyxin B.
Pyocins from Pseudomonas aeruginosa were used to select several lipopolysaccharide (LPS) mutants of Neisseria gonorrhoeae strain FA19. Three classes of LPS mutans were found in the initial group selected for study. The LPS of one class lacked galactose. That of a second group lacked the typical heptose found in the parental LPS, was reduced in glucose, galactose, and N-acetylglucosamine content, appeared to contain a new unidentified sugar component, and consisted of two species of LPS separable on sodium dodecyl sulfate-polyacrylamide gels. The LPS of a third strain lacked the heptose, glucose, galactose, and N-acetylglucosamine found in the oligosaccharide portion of parental FA19 LPS. The minimal inhibitory concentration for polymyxin B of the mutant strains was 3 to 4 times that of the parental strain. The strains lacking only galactose were as resistant as the parent to the bactericidal action of normal human serum, but cells of the other two classes were quickly killed by serum. Gonococcal LPS thus appears to be important in determining phenotypic properties of the cells.


Predictors of progression of HRCT diagnosed fibrosing alveolitis in patients with rheumatoid arthritis.
Fibrosing alveolitis (FA) is the most serious pleuropulmonary extra-articular feature of rheumatoid arthritis (RA). Features that predict progression of FA in patients with RA have not yet been determined. To identify clinical features that predict progressive FA in patients with RA. An unselected cohort of 29 patients with RA and FA confirmed by high resolution computed tomography (HRCT) were studied prospectively for 24 months. Three monthly clinical assessment, four monthly pulmonary function tests, and yearly HRCT scanning was undertaken on these patients. Progressive FA was defined as >15% fall in carbon monoxide transfer factor (TLCO) with evidence of increasing FA on HRCT or death as a result of FA. During 24 months of follow up 10/29 (34%) patients had progressive FA. Progression on HRCT was seen as acute ground glass exacerbations or increasing reticular pattern lung involvement. Progressive FA was associated with the presence of bibasal crackles (p=0.041), TLCO (p=0.001), and extent (p=0.026) and distribution (p=0.031) of lung involvement on HRCT at initial presentation. When multiple logistic regression was used, only TLCO remained significant. Receiver operator curve analysis was employed to identify presenting TLCO of progressive FA. A TLCO <54% of the predicted value demonstrated 80% sensitivity and 93% specificity in predicting progressive FA. A TLCO <54% of the predicted value is a highly specific predictor of disease progression.


Evidence for an induced plasma membrane mating receptor in the myxomycete Didymium iridis.
Haploid myxamoeboid mating types, CR5-11A11 and HON 1-2A1, of the acellular myxomycete Didymium iridis, were isolated and grown in liquid culture. Previously it has been postulated that a molecule, possibly a hormone, is responsible for the induction of mating competency through receptor site synthesis. The intention of this study was to isolate the molecule and to determine its mode of action. Experiments were designed in order to learn whether it acts only upon the cells which produce it (self-induction) or does it have an effect only on opposite mating types (cross-induction). It was found that plasmodia can only form on solid media, although zygotes are readily formed in liquid media. Moreover, competency of cells to fuse, or to form receptors required that they be haploid and in a specific phase of the cell cycle, namely G1 of interphase. The use of high pressure liquid chromatography techniques was also employed in order to investigate the inducer molecule. It was demonstrated that the inducer molecule was similarly produced by both mating types, and its production was essentially paralleled by cell numbers. It was also discovered that mating competency is self-induced and these results are discussed.


Size and homology of the genomes of leprosy-derived corynebacteria, Mycobacterium leprae, and other corynebacteria and mycobacteria.
The genomes of Mycobacterium leprae and leprosy-derived corynebacteria (LDC), which have a similar base composition of guanine + cytosine 56 mol %, have been compared with those of reference bacteria of the CMN group (genera Corynebacterium, Mycobacterium, Nocardia). Genome sizes of three LDC strains were (1.2-2.5) x 10(6) base pairs. DNA from four of seven LDC strains examined had homology levels greater than 60%. Two other strains had a homology of 40% when compared with the CMN strains and one strain was distinctly different. The DNA from all seven LDC strains gave 0.3-18% hybridisation with that of M. leprae, 5-16% with reference corynebacteria, 5-12% with M. bovis, and 2-8% with Nocardia caviae. The small size of the LDC genome and its unrelatedness to those of M. leprae and organisms of the CMN group shows the uniqueness of LDC.


MicroRNA: A matter of life or death.
Progressive cell loss due to apoptosis is a pathological hallmark implicated in a wide spectrum of degenerative diseases such as heart disease, atherosclerotic arteries and hypertensive vessels, Alzheimer's disease and other neurodegenerative disorders. Tremendous efforts have been made to improve our understanding of the molecular mechanisms and signaling pathways involved in apoptosistic cell death. Once ignored completely or overlooked as cellular detritus, microRNAs (miRNAs) that were discovered only a decade ago, have recently taken many by surprise. The importance of miRNAs has steadily gained appreciation and miRNA biology has exploded into a massive swell of interest with enormous range and potential in almost every biological discipline because of their widespread expression and diverse functions in both animals and humans. It has been established that miRNAs are critical regulators of apoptosis of various cell types. These small molecules act by repressing the expression of either the proapoptotic or antiapoptotic genes to produce antiapoptotic or proapoptotic effects. Appealing evidence has been accumulating for the involvement of miRNAs in human diseases associated with apoptotic cell death and the potential of miRNAs as novel therapeutic targets for the treatment of the diseases. This editorial aims to convey this message and to boost up the research interest by providing a timely, comprehensive overview on regulation of apoptosis by miRNAs and a synopsis on the pathophysiologic implications of this novel regulatory network based on the currently available data in the literature. It begins with a brief introduction to apoptosis and miRNAs, followed by the description of the fundamental aspects of miRNA biogenesis and action, and the role of miRNAs in regulating apoptosis of cancer cells and cardiovascular cells. Speculations on the development of miRNAs as potential therapeutic targets are also presented. Remarks are also provided to point out the unanswered questions and to outline the new directions for the future research of the field.


Fixation of distal femoral osteotomies with self-reinforced poly(L/DL)lactide 70:30 and self-reinforced poly(L/DL)lactide 70: 30/bioactive glass composite rods. an experimental study on rabbits.
Two self-reinforced poly(L/DL)lactide 70:30 or self-reinforced poly (L/DL)lactide 70:30/ bioactive glass (SR-P(L/DL)LA/bioactive glass) composite rods (2 mm x 40 mm) were implanted into the dorsal subcutaneous tissue and osteotomies of the distal femur were fixed with these rods (2 mm x 26 mm) in 36 rabbits. The follow-up times varied from 3 to 100 weeks. After the animals were killed, three-point bending and shear tests and molecular weight measurements were performed for subcutaneously placed rods. Radiological, histological, histomorphometrical, microradiographic and oxytetracycline-fluorescence studies of the osteotomized and intact control femora were performed. After 12 weeks the SR-P(L/DL)LA rods had fragmented into pieces and the mechanical properties could not be measured. The SR-P(L/DL)LA/bioactive glass rods lost their mechanical properties slower, and at 24 weeks the bending strength had decreased by 39% and the shear strength by 50%. After that the mechanical properties of the SR-P(L/DL)LA/bioactive glass rods could not be measured. All osteotomies healed well, and no gross signs of inflammatory reactions were observed. One slight displacement was seen in the three-week follow-up group with SR-P(L/DL)LA rods. Signs of resorption of the implants were seen after 48 weeks in the SR-P(L/DL)LA group and after 24 weeks in the SR-P(L/DL)LA/bioactive glass group. The SR-P(L/DL)LA/bioactive glass rods were almost totally resorbed from the bone at 100 weeks. The present investigation showed that the mechanical strength and fixation properties of the SR-P(L/DL)LA and the SR-P(L/DL)LA/bioactive glass composite rods are suitable for fixation of cancellous bone osteotomies in rabbits.


[Biological mechanisms and genes involved in puberty].
Puberty is an important step in human development. Onset of puberty, including neurobiological mechanisms important for the increase of hypothalamic GnRH pulses remains a mystery. After birth, GnRH secretion remains elevated and then decreases during childhood regardless of any steroid gonadal feedback. This period of quiescence of the gonadotropic axis during childhood is linked to a central inhibition of GnRH secretion which is replaced by an activator tone at puberty. The study of the pathology of the pubertal timing, including delayed puberty led to the discovery of new genes involved in the migration of GnRH neurons and genes involved in the neuroendocrine regulation of the gonadotropic axis. Recently, the emphasis on the importance of the kiss/GPR54 system in modulating control of the gonadotropic axis at puberty has recently emerged from Human genetics studies.


Alcohol and suicide in 14 European countries.
To test the hypothesis that a positive population-level relationship between alcohol and suicide is more likely to be found in dry drinking cultures (as indicated by consumption level) than in wet drinking cultures. Gender- and age-specific suicide rates in 14 western European countries were analysed in relation to per capita alcohol consumption employing the Box-Jenkins technique for time series analysis. The country-specific estimates were pooled into low-, medium- and high-consumption countries. Suicide mortality data for 5-year age groups were converted into gender- and age-specific mortality rates. Alcohol sales expressed as litres of 100% alcohol per year and inhabitants 15 years and older were used as a measure of alcohol consumption. A positive and significant relationship between per capita consumption and gender- and age-specific suicide rates was revealed most often in northern Europe and found least often in southern Europe. A stronger absolute alcohol effect for men was found only in northern Europe, whereas the relative alcohol effect was somewhat stronger for women in both northern and central Europe. Also, the suicide rate in younger age groups was more often significantly related to per capita consumption than suicide among the elder in northern and central Europe but not in southern Europe. The population-level association between alcohol and suicide is conditioned by cultural factors. In general, the suicide rate tends to be more responsive to changes in alcohol consumption in drinking cultures characterized by a low post-war per capita consumption compared to drinking cultures with higher consumption levels. The findings give support to the hypothesis derived from previous theoretical and empirical work, suggesting that suicide and alcohol is more closely connected in dry cultures than in wet cultures.


Preference Reversals in Decision Making Under Risk are Accompanied by Changes in Attention to Different Attributes.
Recent work has shown that visual fixations reflect and influence trial-to-trial variability in people's preferences between goods. Here we extend this principle to attribute weights during decision making under risk. We measured eye movements while people chose between two risky gambles or bid on a single gamble. Consistent with previous work, we found that people exhibited systematic preference reversals between choices and bids. For two gambles matched in expected value, people systematically chose the higher probability option but provided a higher bid for the option that offered the greater amount to win. This effect was accompanied by a shift in fixations of the two attributes, with people fixating on probabilities more during choices and on amounts more during bids. Our results suggest that the construction of value during decision making under risk depends on task context partly because the task differentially directs attention at probabilities vs. amounts. Since recent work demonstrates that neural correlates of value vary with visual fixations, our results also suggest testable hypotheses regarding how task context modulates the neural computation of value to generate preference reversals.


Quantifying soil moisture impacts on light use efficiency across biomes.
Terrestrial primary productivity and carbon cycle impacts of droughts are commonly quantified using vapour pressure deficit (VPD) data and remotely sensed greenness, without accounting for soil moisture. However, soil moisture limitation is known to strongly affect plant physiology. Here, we investigate light use efficiency, the ratio of gross primary productivity (GPP) to absorbed light. We derive its fractional reduction due to soil moisture (fLUE), separated from VPD and greenness changes, using artificial neural networks trained on eddy covariance data, multiple soil moisture datasets and remotely sensed greenness. This reveals substantial impacts of soil moisture alone that reduce GPP by up to 40% at sites located in sub-humid, semi-arid or arid regions. For sites in relatively moist climates, we find, paradoxically, a muted fLUE response to drying soil, but reduced fLUE under wet conditions. fLUE identifies substantial drought impacts that are not captured when relying solely on VPD and greenness changes and, when seasonally recurring, are missed by traditional, anomaly-based drought indices. Counter to common assumptions, fLUE reductions are largest in drought-deciduous vegetation, including grasslands. Our results highlight the necessity to account for soil moisture limitation in terrestrial primary productivity data products, especially for drought-related assessments.


Clinical and anatomical variables associated in the literature to limb graft occlusion after endovascular aneurysm repair compared to the experience of a tertiary referral center.
Limb graft occlusion (LGO) is the third reason for hospital readmission after endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm. We reviewed the clinical features, incidence, anatomical and devices related predictive factors for LGO after EVAR, and compared them with our experience. EVAR between 2010-2017 were included. Patients with LGO (LGO group) were matched for age and type of endograft with the rest of the entire cohort without LGO (control group). Clinical, anatomical, operative, outcome, and follow-up data were collected. Two hundred seventy-six EVAR, (30 aorto-uniliac), 276 patients. The incidence of LGO was 2.5% (seven limbs, seven patients) at 27±24.6 days. Symptomatic patients were successfully treated. No mortality, limb loss, critical limb ischemia or residual claudication due to LGO was observed. Fifty patients resulted from the matching. Among the predictive factors of LGO between the two groups, significant differences were observed in graft limb oversizing ≥15% (57.1% vs. 8%, P=0.005), or kinking (42.9% vs. 2%, P=0.01), and diameter of the aortic bifurcation <20 mm (71.4% vs. 20%, P=0.01). Logistic regression analysis showed that these three variables increased the risk of LGO (P=0.003, P=0.006, and P=0.01, respectively). The strongest predictive factors of LGO issued from our review were: extension in the external iliac artery, or small diameter; tortuous, angled, and calcific iliac axis; excessive oversizing of the limb graft, or kinking; use of old generation devices; EVAR performed outside the instructions for use. Limb graft oversizing >15%, or kinking, and aortic bifurcation <20 mm appear to be independent predictive factors of LGO.


Chlamydophila pneumoniae Infection and Its Role in Neurological Disorders.
Chlamydophila pneumoniae is an intracellular pathogen responsible for a number of different acute and chronic infections. The recent deepening of knowledge on the biology and the use of increasingly more sensitive and specific molecular techniques has allowed demonstration of C. pneumoniae in a large number of persons suffering from different diseases including cardiovascular (atherosclerosis and stroke) and central nervous system (CNS) disorders. Despite this, many important issues remain unanswered with regard to the role that C. pneumoniae may play in initiating atheroma or in the progression of the disease. A growing body of evidence concerns the involvement of this pathogen in chronic neurological disorders and particularly in Alzheimer's disease (AD) and Multiple Sclerosis (MS). Monocytes may traffic C. pneumoniae across the blood-brain-barrier, shed the organism in the CNS and induce neuroinflammation. The demonstration of C. pneumoniae by histopathological, molecular and culture techniques in the late-onset AD dementia has suggested a relationship between CNS infection with C. pneumoniae and the AD neuropathogenesis. In particular subsets of MS patients, C. pneumoniae could induce a chronic persistent brain infection acting as a cofactor in the development of the disease. The role of Chlamydia in the pathogenesis of mental or neurobehavioral disorders including schizophrenia and autism is uncertain and fragmentary and will require further confirmation.


Biochemical and spatial coincidence in the provisional Ser/Thr protein kinase interaction network of Mycobacterium tuberculosis.
Many Gram-positive bacteria coordinate cellular processes by signaling through Ser/Thr protein kinases (STPKs), but the architecture of these phosphosignaling cascades is unknown. To investigate the network structure of a prokaryotic STPK system, we comprehensively explored the pattern of signal transduction in the Mycobacterium tuberculosis Ser/Thr kinome. Autophosphorylation is the dominant mode of STPK activation, but the 11 M. tuberculosis STPKs also show a specific pattern of efficient cross-phosphorylation in vitro. The biochemical specificity intrinsic to each kinase domain was used to map the provisional signaling network, revealing a three-layer architecture that includes master regulators, signal transducers, and terminal substrates. Fluorescence microscopy revealed that the STPKs are specifically localized in the cell. Master STPKs are concentrated at the same subcellular sites as their substrates, providing additional support for the biochemically defined network. Together, these studies imply a branched functional architecture of the M. tuberculosis Ser/Thr kinome that could enable horizontal signal spreading. This systems-level approach provides a biochemical and spatial framework for understanding Ser/Thr phospho-signaling in M. tuberculosis, which differs fundamentally from previously defined linear histidine kinase cascades.


Hyaluronic Acid (HA) Viscosupplementation on Synovial Fluid Inflammation in Knee Osteoarthritis: A Pilot Study.
This study examined the changes in synovial fluid levels of cytokines, oxidative stress and viscosity six months after intraarticular hyaluronic acid (HA) treatment in adults and elderly adults with knee osteoarthritis (OA). This was a prospective, repeated-measures study design in which patients with knee OA were administered 1% sodium hyaluronate. Patients (N=28) were stratified by age (adults, 50-64 years and elderly adults, ≥65 years). Ambulatory knee pain values and self-reported physical activity were collected at baseline and month six. Knee synovial fluid aspirates were collected at baseline and at six months. Fluid samples were analyzed for pro-inflammatory cytokines (interleukins 1β, 6,8,12, tumor necrosis factor-α, monocyte chemotactic protein), anti-inflammatory cytokines (interleukins 4, 10 13), oxidative stress (4-hydroxynonenal) and viscosity at two different physiological shear speeds 2.5Hz and 5Hz. HA improved ambulatory knee pain in adults and elderly groups by month six, but adults reported less knee pain-related interference with participation in exercise than elderly adults. A greater reduction in TNF-α occurred in adults compared to elderly adults (-95.8% ± 7.1% vs 19.2% ± 83.8%, respectively; p=.044). Fluid tended to improve at both shear speeds in adults compared to the elderly adults. The reduction in pain severity correlated with the change in IL-1β levels by month six (r= -.566; p=.044). Reduction of knee pain might be due to improvements in synovial fluid viscosity and inflammation. Cartilage preservation may be dependent on how cytokine, oxidative stress profiles and viscosity change over time.


Phase II trial of radiosurgery to magnetic resonance spectroscopy-defined high-risk tumor volumes in patients with glioblastoma multiforme.
To determine the efficacy of a Gamma Knife stereotactic radiosurgery (SRS) boost to areas of high risk determined by magnetic resonance spectroscopy (MRS) functional imaging in addition to standard radiotherapy for patients with glioblastoma (GBM). Thirty-five patients in this prospective Phase II trial underwent surgical resection or biopsy for a GBM followed by SRS directed toward areas of MRS-determined high biological activity within 2 cm of the postoperative enhancing surgical bed. The MRS regions were determined by identifying those voxels within the postoperative T2 magnetic resonance imaging volume that contained an elevated choline/N-acetylaspartate ratio in excess of 2:1. These voxels were marked, digitally fused with the SRS planning magnetic resonance image, targeted with an 8-mm isocenter per voxel, and treated using Radiation Therapy Oncology Group SRS dose guidelines. All patients then received conformal radiotherapy to a total dose of 60 Gy in 2-Gy daily fractions. The primary endpoint was overall survival. The median survival for the entire cohort was 15.8 months. With 75% of recursive partitioning analysis (RPA) Class 3 patients still alive 18 months after treatment, the median survival for RPA Class 3 has not yet been reached. The median survivals for RPA Class 4, 5, and 6 patients were 18.7, 12.5, and 3.9 months, respectively, compared with Radiation Therapy Oncology Group radiotherapy-alone historical control survivals of 11.1, 8.9, and 4.6 months. For the 16 of 35 patients who received concurrent temozolomide in addition to protocol radiotherapeutic treatment, the median survival was 20.8 months, compared with European Organization for Research and Treatment of Cancer historical controls of 14.6 months using radiotherapy and temozolomide. Grade 3/4 toxicities possibly attributable to treatment were 11%. This represents the first prospective trial using selective MRS-targeted functional SRS combined with radiotherapy for patients with GBM. This treatment is feasible, with acceptable toxicity and patient survivals higher than in historical controls. This study can form the basis for a multicenter, randomized trial.


Source, fate and management of recreational fishing marine debris.
Marine debris, directly and indirectly, threatens marine habitat and biota. Fishing activity is generally recognised as a contributor to marine debris, but the relative input from recreational fishing remains unassessed. Here we provide the first comprehensive literature review of recreational fishing marine debris (RFMD) on a global scale. A systematic literature review identified 70 studies related to RFMD, and plastic and metal respectively were the dominant debris materials found. Nearshore coastal areas and reefs, acted as both sources and sinks of RFMD and a diverse suite of potential impacts such as ghost fishing and entanglement were identified at local scales. Overall, research of RFMD is lacking globally, however, its role in marine debris input is likely underestimated. We recommend more research on the volumes and risks, using a standardised classification approach. Where intervention is required, we suggest cooperative approaches between the sector and authorities.


Icing on the Cake: Imidazole-Anchored Strategy To Enhance the Proton Conductivity of Two Isostructural Ce(IV)/Hf(IV) Metal-Organic Frameworks.
In the field of proton conduction, the acquisition of crystalline metal-organic frameworks (MOFs) with high stability and ultrahigh proton conductivity has been of great research value and is worth continuous exploration. Here, we greenly synthesized a three-dimensional porous MOF (MOF-801-Ce) by using [(NH4)2Ce(NO3)6 and fumaric acid as starting materials and solvothermally synthesized Hf-UiO-66-NO2 by using HfCl4 and 2-nitroterephthalic acid as starting materials. A series of measurements have shown that both MOFs exhibit good water stability, acid-base stability, and thermal stability and demonstrate outstanding proton conductivity. At 100 °C and 98% relative humidity (RH), the proton conductivities (σ) could be 2.59 × 10-3 S·cm-1 for MOF-801-Ce and 0.89 × 10-3 S·cm-1 for Hf-UiO-66-NO2. To pursue higher proton conductivity, we further adopted the evaporation approach to encapsulate imidazole molecules in the pores of the two compounds, achieving the imidazole-encapsulated MOFs, Im@MOF-801-Ce and Im@Hf-UiO-66-NO2. As expected, their σ values were significantly boosted by almost an order of magnitude up to 10-2 S·cm-1. Finally, their proton-conductive mechanisms were explored in light of the structural information, gas adsorption/desorption, and other tests. The outstanding structural stability of these MOFs and their durability of the proton conduction capability manifested that they have great promise in electrochemical fields.


Use of complementary and alternative medical therapies among racial and ethnic minority adults: results from the 2002 National Health Interview Survey.
Complementary and alternative medicine (CAM) use among ethnic minority populations is poorly understood. We sought to examine CAM use in Hispanics, non-Hispanic blacks and non-Hispanic whites. We analyzed data from the Alternative Health Supplement to the 2002 National Health Interview Survey (NHIS), including information on 19 different CAM therapies used in the past 12 months. An estimated 34% of Hispanic, non-Hispanic black and non-Hispanic white adults in the United States used at least one CAM therapy (excluding prayer) during the prior 12 months (2002). CAM use was highest for non-Hispanic whites (36%), followed by Hispanics (27%) and non-Hispanic blacks (26%). Non-Hispanic whites were more likely to use herbal medicine, relaxation techniques and chiropractic more frequently than Hispanics and non-Hispanic blacks. After controlling for other sociodemographic factors, Hispanic and non-Hispanic black races/ethnicities were associated with less CAM use, with adjusted odds ratios (95% confidence intervals) of 0.78 (0.70, 0.87) and 0.71 (0.65, 0.78), respectively. Hispanics cited using CAM because conventional medical treatments were too expensive more frequently than non-Hispanic blacks or whites. Hispanics had the highest provider nondisclosure rates (68.5%), followed by non-Hispanic blacks (65.1%) and non-Hispanic whites (58.1%). Excluding prayer, Hispanics and non-Hispanic blacks used CAM less frequently than non-Hispanic whites and were less likely to disclose their use to their healthcare provider. Further research is needed to improve our understanding of the disparities in CAM use.


Multiple object tracking in molecular bioimaging by Rao-Blackwellized marginal particle filtering.
Time-lapse fluorescence microscopy imaging has rapidly evolved in the past decade and has opened new avenues for studying intracellular processes in vivo. Such studies generate vast amounts of noisy image data that cannot be analyzed efficiently and reliably by means of manual processing. Many popular tracking techniques exist but often fail to yield satisfactory results in the case of high object densities, high noise levels, and complex motion patterns. Probabilistic tracking algorithms, based on Bayesian estimation, have recently been shown to offer several improvements over classical approaches, by better integration of spatial and temporal information, and the possibility to more effectively incorporate prior knowledge about object dynamics and image formation. In this paper, we extend our previous work in this area and propose an improved, fully automated particle filtering algorithm for the tracking of many subresolution objects in fluorescence microscopy image sequences. It involves a new track management procedure and allows the use of multiple dynamics models. The accuracy and reliability of the algorithm are further improved by applying marginalization concepts. Experiments on synthetic as well as real image data from three different biological applications clearly demonstrate the superiority of the algorithm compared to previous particle filtering solutions.


Effect of glucose supply on ovine uteroplacental glucose metabolism.
To test the hypothesis that glucose supply to the uteroplacenta (UP) regulates UP glucose metabolism into oxidative and nonoxidative pathways, we studied eight late-gestation pregnant sheep at low (LG) and high (HG) maternal glucose concentrations (G(M)), using Fick principle and tracer glucose methodology. UP glucose consumption (UPGC) correlated directly with G(M) (r = 0.75, P = 0.0006), and UP glucose decarboxylation (r = 0.80, P = 0.0001), and lactate production (r = 0.90, P = 0.0001) rates were directly correlated with UPGC. The combined fractional production rate for lactate, fructose, and CO(2) from UPGC was the same in LG and HG periods. The fraction of UP oxygen consumption used for glucose oxidation increased by about 50% from LG to HG conditions; however, there was no change in UP oxygen consumption. Nearly half of UPGC was not accounted for by lactate, fructose, and CO(2) production, and about two-thirds of UP oxygen consumption was not accounted for by immediate oxidation of glucose carbon just taken up by the UP. These results indicate that glucose supply directly regulates UP glucose oxidative metabolism and that there is a reciprocal relationship between UP glucose oxidation and the oxidation of other substrates.


Exploring Cognitive Concomitants of Mental Fatigue in Patients with Coronary Artery Disease.
Fatigue and reduced exercise capacity are common concomitants of coronary artery disease (CAD). They are known to be associated with the deterioration in mental health, including emotional and cognitive status. However, the precise nature of the inter-relationship is poorly understood. The aim of this study was to investigate the relationship between fatigue and exercise capacity on the one hand and changes in cognitive functioning on the other, to generate new heuristics for clinical management and outcome prediction of CAD. A cross-sectional study included 827 in-patients (58 ± 9 years, 75% men) with CAD. Patients were evaluated for demographic, cardiac characteristics, and exercise capacity. The Multidimensional Fatigue Inventory-20 was used to assess fatigue, the Mini Mental State Examination for global cognitive function, the Digit Span Test, Digit Symbol Test, and Trail Making Test for executive aspects of cognitive functioning, and the Hospital Anxiety and Depression Scale for anxiety and depression symptom severity. Using multiple regression analysis, after adjusting for possible confounders such as anxiety and depression, mental fatigue was associated with several executive aspects of cognitive function including short-term memory (Digit Symbol Test pairs recalled correctly [β = -0.127, p < 0.005]), psychomotor performance (time to complete the Digit Symbol Test [β = 0.089, p < 0.03]), and cognitive processing speed (Trail Making Test A [β = 0.081, p < 0.05]). In rehabilitating CAD patients, certain aspects of executive functioning were independently associated with mental fatigue. These findings suggest that the subjective experience of mental fatigue, rather than reduced exercise capacity, is significantly associated with cognitive function.