Natural history of lymph pumping pressure after pelvic lymphadenectomy.
Lower limb lymphedema is difficult to prevent and diagnose early because its natural history is unclear. Therefore, the aim of this study was to clarify its pathogenesis and to identify risk factors that may lead to early diagnosis. In 29 patients, aged 25 to 74 years with cervical, uterine, or ovarian cancer who underwent pelvic lymphadenectomy, indocyanine green fluorescence lymphangiography was performed with an infrared camera system, and lymph pumping pressure was measured indirectly preoperatively, and one, two, three, and six months postoperatively. Of these 29 patients, 22 (75.9%) completed the examinations. In the non-lymphedema group, the average lymph pumping pressure did not change significantly at postoperative follow-up compared with preoperative values. On the other hand, lymph pumping pressure increased at various time points in five patients who developed early lymphatic changes with dermal diffusion at the level of the proximal femur. An increase in lymph flow path resistance due to pelvic lymphadenectomy resulted in an initial increase in lymph pumping pressure, followed by a subsequent decrease, in the early lymphatic changes group. This trend in the pressure change signifies that the lymph vessels became dysfunctional as they were overwhelmed by the overload condition and this feature may be a clinically useful signal for the early diagnosis of developing lymphedema.


Genomic and immune profiling of pre-invasive lung adenocarcinoma.
Adenocarcinoma in situ and minimally invasive adenocarcinoma are the pre-invasive forms of lung adenocarcinoma. The genomic and immune profiles of these lesions are poorly understood. Here we report exome and transcriptome sequencing of 98 lung adenocarcinoma precursor lesions and 99 invasive adenocarcinomas. We have identified EGFR, RBM10, BRAF, ERBB2, TP53, KRAS, MAP2K1 and MET as significantly mutated genes in the pre/minimally invasive group. Classes of genome alterations that increase in frequency during the progression to malignancy are revealed. These include mutations in TP53, arm-level copy number alterations, and HLA loss of heterozygosity. Immune infiltration is correlated with copy number alterations of chromosome arm 6p, suggesting a link between arm-level events and the tumor immune environment.


Fish distributions and nutrient cycling in streams: can fish create biogeochemical hotspots?
Rates of biogeochemical processes often vary widely in space and time, and characterizing this variation is critical for understanding ecosystem functioning. In streams, spatial hotspots of nutrient transformations are generally attributed to physical and microbial processes. Here we examine the potential for heterogeneous distributions of fish to generate hotspots of nutrient recycling. We measured nitrogen (N) and phosphorus (P) excretion rates of 47 species of fish in an N-limited Neotropical stream, and we combined these data with population densities in each of 49 stream channel units to estimate unit- and reach-scale nutrient recycling. Species varied widely in rates of N and P excretion as well as excreted N:P ratios (6-176 molar). At the reach scale, fish excretion could meet >75% of ecosystem demand for dissolved inorganic N and turn over the ambient NH4 pool in <0.3 km. Areal N excretion estimates varied 47-fold among channel units, suggesting that fish distributions could influence local N availability. P excretion rates varied 14-fold among units but were low relative to ambient concentrations. Spatial variation in aggregate nutrient excretion by fish reflected the effects of habitat characteristics (depth, water velocity) on community structure (body size, density, species composition), and the preference of large-bodied species for deep runs was particularly important. We conclude that the spatial distribution of fish could indeed create hotspots of nutrient recycling during the dry season in this species-rich tropical stream. The prevalence of patchy distributions of stream fish and invertebrates suggests that hotspots of consumer nutrient recycling may often occur in stream ecosystems.


An inverse latitudinal gradient in speciation rate for marine fishes.
Far more species of organisms are found in the tropics than in temperate and polar regions, but the evolutionary and ecological causes of this pattern remain controversial1,2. Tropical marine fish communities are much more diverse than cold-water fish communities found at higher latitudes3,4, and several explanations for this latitudinal diversity gradient propose that warm reef environments serve as evolutionary 'hotspots' for species formation5-8. Here we test the relationship between latitude, species richness and speciation rate across marine fishes. We assembled a time-calibrated phylogeny of all ray-finned fishes (31,526 tips, of which 11,638 had genetic data) and used this framework to describe the spatial dynamics of speciation in the marine realm. We show that the fastest rates of speciation occur in species-poor regions outside the tropics, and that high-latitude fish lineages form new species at much faster rates than their tropical counterparts. High rates of speciation occur in geographical regions that are characterized by low surface temperatures and high endemism. Our results reject a broad class of mechanisms under which the tropics serve as an evolutionary cradle for marine fish diversity and raise new questions about why the coldest oceans on Earth are present-day hotspots of species formation.


ProForma: A Standard Proteoform Notation.
The Consortium for Top-Down Proteomics (CTDP) proposes a standardized notation, ProForma, for writing the sequence of fully characterized proteoforms. ProForma provides a means to communicate any proteoform by writing the amino acid sequence using standard one-letter notation and specifying modifications or unidentified mass shifts within brackets following certain amino acids. The notation is unambiguous, human-readable, and can easily be parsed and written by bioinformatic tools. This system uses seven rules and supports a wide range of possible use cases, ensuring compatibility and reproducibility of proteoform annotations. Standardizing proteoform sequences will simplify storage, comparison, and reanalysis of proteomic studies, and the Consortium welcomes input and contributions from the research community on the continued design and maintenance of this standard.


Technical refinements in small bowel transplantation.
This review focuses on the recently described or revised refinements or innovations in small bowel transplantation. Changes in donor selection criteria; cadaveric procurement techniques; organ preservation solutions; management of the recipient abdominal wall; technical modifications, pitfalls and recommendations to be applied during the engraftment as well as intestinal living donation will be covered. Intestinal transplantation has evolved over time to become a clinically accepted therapy for patients with intestinal failure. Short- and long-term results have improved. The surgical procedures have been standardized and the applications broaden, but there have been recently published refinements that might affect the future results of clinical intestinal transplantation and guide research.


A cross sectional study investigating the association between exposure to food outlets and childhood obesity in Leeds, UK.
Current UK policy in relation to the influence of the 'food environment' on childhood obesity appears to be driven largely on assumptions or speculations because empirical evidence is lacking and findings from studies are inconsistent. The aim of this study was to investigate the number of food outlets and the proximity of food outlets in the same sample of children, without solely focusing on fast food. Cross sectional study over 3 years (n = 13,291 data aggregated). Body mass index (BMI) was calculated for each participant, overweight and obesity were defined as having a BMI >85(th) (sBMI 1.04) and 95(th) (sBMI 1.64) percentiles respectively (UK90 growth charts). Home and school neighbourhoods were defined as circular buffers with a 2 km Euclidean radius, centred on these locations. Commuting routes were calculated using the shortest straight line distance, with a 2 km buffer to capture varying routes. Data on food outlet locations was sourced from Leeds City Council covering the study area and mapped against postcode. Food outlets were categorised into three groups, supermarkets, takeaway and retail. Proximity to the nearest food outlet in the home and school environmental domain was also investigated. Age, gender, ethnicity and deprivation (IDACI) were included as covariates in all models. There is no evidence of an association between the number of food outlets and childhood obesity in any of these environments; Home Q4 vs. Q1 OR = 1.11 (95% CI = 0.95-1.30); School Q4 vs. Q1 OR = 1.00 (95% CI 0.87 - 1.16); commute Q4 vs. Q1 OR = 0.1.00 (95% CI 0.83 - 1.20). Similarly there is no evidence of an association between the proximity to the nearest food outlet and childhood obesity in the home (OR = 0.77 [95% CI = 0.61 - 0.98]) or the school (OR = 1.01 [95% CI 0.84 - 1.23]) environment. This study provides little support for the notion that exposure to food outlets in the home, school and commuting neighbourhoods increase the risk of obesity in children. It seems that the evidence is not well placed to support Governmental interventions/recommendations currently being proposed and that policy makers should approach policies designed to limit food outlets with caution.


Anion binding, electrochemistry and solvatochromism of β-brominated oxoporphyrinogens.
Effects of macrocycle bromination on the structural, electrochemical and anion binding properties of 5,10,15,20-tetrakis(3,5-di-t-butyl-4-oxo-cyclohexa-2,5-dienylidene)porphyrinogen, OxP, are reported. Bromination of 5,10,15,20-tetrakis(3,5-di-t-butyl-4-hydroxyphenyl)-porphinatocopper(II), [T(DtBHP)P]Cu(II) yielded β-Br8OxP, which was N-alkylated to β-Br8OxPBz2 and β-Br8OxPBz4 (where Bz = 4-bromobenzyl). β-Br8OxPBz2 crystallizes in orthorhombic space group Pccn [a = 23.5535(17) Å, b = 19.3587(14) Å c = 20.9760(15) Å, V = 9564.3(12) Å3]. It has a calix[4]pyrrole-like structure with a saddle conformation and two molecules of methanol occupy a central binding site made up of the non-alkylated pyrrole N–H groups. Computational and electrochemical studies revealed widening HOMO–LUMO band gaps for the brominated compounds over the non-brominated analogues consistent with the observed hypsochromic shifts in electronic absorption spectra. Solvatochromic and chromogenic effects on anion binding were both observed for β-Br8OxP and β-Br8OxPBz2 with binding affinities of anions being greater than those observed for the corresponding OxP and OxPBz2. Colorimetric sensor studies suggest that the OxP compounds reported here are possible candidates for use in the design of optoelectronic noses for detection of anions and anionic analyte species of biological interest.


Factors affecting treatment decisions for Class I malocclusions.
Orthodontic treatment planning requires skill and expertise with considerable practice variations. The aims of this study were to review retrospectively the pretreatment records of patients with Class I malocclusion and to identify variables that could play a role in the treatment decision. From the available records of 1500 orthdontic patients, the pretreatment records of 202 patients were selected at random. Inclusion and exclusion criteria were applied, and the surviving records were divided into extraction (n = 92) and nonextraction (n = 92) treatment groups. Skeletal, dental, and soft tissue measurements were obtained from pretreatment lateral cephalograms and dental casts of subjects with bilateral Class I molar relationships. Data were statistically analyzed by binary logistic regression tests. The results showed that the variables of lower anterior facial height, E-plane to upper lip, and maxillary and mandibular incisor inclinations were significantly increased in the extraction group (P <0.05), whereas spacing in the mandibular arch and increased overbite were statistically significant in the nonextraction treatment group (P <0.05). According to the model, the odds of nonextraction treatment are 1.29 and 1.24 times that of extraction treatment for every 1-mm increase in overbite and spacing in the mandibular arch, respectively. Vertical facial pattern, overbite, mandibular tooth size-arch length discrepancy, lip position, and maxillary and mandibular incisor inclinations are a few of the important variables that should not be overlooked when planning orthodontic treatment. The findings of this study could facilitate the treatment planning process for patients with Class I malocclusion.


Combinatorial pharmacogenetic interactions of bucindolol and β1, α2C adrenergic receptor polymorphisms.
Pharmacogenetics involves complex interactions of gene products affecting pharmacodynamics and pharmacokinetics, but there is little information on the interaction of multiple genetic modifiers of drug response. Bucindolol is a β-blocker/sympatholytic agent whose efficacy is modulated by polymorphisms in the primary target (β(1) adrenergic receptor [AR] Arg389 Gly on cardiac myocytes) and a secondary target modifier (α(2C) AR Ins [wild-type (Wt)] 322-325 deletion [Del] on cardiac adrenergic neurons). The major allele homozygotes and minor allele carriers of each polymorphism are respectively associated with efficacy enhancement and loss, creating the possibility for genotype combination interactions that can be measured by clinical trial methodology. In a 1,040 patient substudy of a bucindolol vs. placebo heart failure clinical trial, we tested the hypothesis that combinations of β(1)389 and α(2C)322-325 polymorphisms are additive for both efficacy enhancement and loss. Additionally, norepinephrine (NE) affinity for β(1)389 AR variants was measured in human explanted left ventricles. The combination of β(1)389 Arg+α(2C)322-325 Wt major allele homozygotes (47% of the trial population) was non-additive for efficacy enhancement across six clinical endpoints, with an average efficacy increase of 1.70-fold vs. 2.32-fold in β(1)389 Arg homozygotes+α(2C)322-325 Del minor allele carriers. In contrast, the minor allele carrier combination (13% subset) exhibited additive efficacy loss. These disparate effects are likely due to the higher proportion (42% vs. 8.7%, P = 0.009) of high-affinity NE binding sites in β(1)389 Arg vs. Gly ARs, which converts α(2C)Del minor allele-associated NE lowering from a therapeutic liability to a benefit. On combination, the two sets of AR polymorphisms 1) influenced bucindolol efficacy seemingly unpredictably but consistent with their pharmacologic interactions, and 2) identified subpopulations with enhanced (β(1)389 Arg homozygotes), intermediate (β(1)389 Gly carriers+α(2C)322-325 Wt homozygotes), and no (β(1)389 Gly carriers+α(2C)322-325 Del carriers) efficacy.


Innovative oral spray-dried Idebenone systems to improve patient compliance.
Idebenone is a high permeable drug with very slight water solubility that affects the dissolution rate in the biological fluids, causing an irregular and limited in vivo absorption after oral administration. Moreover, it is marketed in Europe as tablets equivalent to 150 mg, with the consequent administration of multiple dose of solid unit to obtain the correct dose, a deterrent for the patients' compliance. According to these considerations, our goal was to develop spray-dried microparticles using a soluble β-cyclodextrin (CD) polymer and an enhancer of dissolution rate, such as carboxymethyl cellulose, to obtain a formulation easily dosable and soluble in water. The complex in solution was evaluated by phase solubility studies and the Idebenone/CD molar ratio selected was 1:1. According to Higuchi and Connors, adding carboxymethyl cellulose, a Bs-type profile was obtained. This result was due to the presence of carboxymethyl cellulose that competes with the CD in forming Idebenone microsystems, reducing of 10-fold the formulation bulk. UV-Vis absorption, (1)H nuclear magnetic resonance and circular dichroism showed the formation of the CD/Idebenone inclusion complex confirmed also by differential scanning calorimetry, Fourier transform infrared spectroscopy and fluorescence microscope (FM). The water solubility data and the in vitro dissolution tests performed in simulated gastric fluid, showed an increase of the drug water interaction due to the presence of the CD and carboxymethyl cellulose, both able to improve drug wettability, water solubility and dissolution rate. This approach seems to be suitable to produce microsystems which are able to enhance the in vivo absorption of Idebenone after oral administration and to increase the patient compliance.


Peri-implant marginal bone loss reduction with platform-switching components: 5-Year post-loading results of an equivalence randomized clinical trial.
To compare the clinical performance and marginal bone levels of implants restored with platform-switching (PS) or platform-matching (PM) abutments. Adult patients missing two or more adjacent teeth in the posterior mandible received 2-4 CAMLOG SCREW-LINE implants and were randomly allocated to the PM or PS group, receiving the corresponding prosthetic components from surgery onwards. Implants were conventionally loaded with single cemented crowns. Patients were followed annually for 5 years. Outcome measures were marginal bone level changes, implant survival, performance of the prosthetic components and clinical parameters plaque index, sulcus bleeding index and pocket probing depth. Thirty-three patients received 72 implants in the PM group, and thirty-five patients received 74 implants in the PS group. Sixty patients attended the final appointment, 31 had received PS components and 29 had received PM components with 65 and 63 implants, respectively. Global survival rate was 96.6% with no differences between groups (p = 0.647). After 5 years of functional loading, PS restored implants presented 0.23mm (95% CI: [0.03, 0.43], p = 0.025) lower marginal bone level changes. The two groups were declared non-equivalent. Patients requiring implant supported restorations in healed bounded or free end edentulous gaps of the mandible benefit from the use of PS components in terms of peri-implant marginal bone level maintenance, though it may not be clinically noticeable.


Endothelial cell barrier enhancement by ATP is mediated by the small GTPase Rac and cortactin.
ATP is a physiologically relevant agonist released by various sources, including activated platelets, with complex effects mediated via activation of P(2) purinergic receptors. ATP-induced endothelial cell (EC) production of prostacyclin and nitric oxide is recognized, and EC barrier enhancement evoked by ATP has been described. ATP effects on EC barrier function and vascular permeability, however, remain poorly characterized. Although the mechanisms involved are unclear, we previously identified activation of the small GTPase Rac and translocation of cortactin, an actin-binding protein, as key to EC barrier augmentation induced by simvastatin and sphingosine 1-phosphate and therefore examined the role of these molecules in ATP-induced EC barrier enhancement. ATP induced rapid, dose-dependent barrier enhancement in human pulmonary artery EC as measured by transendothelial electrical resistance, with a peak effect appreciable at 25 min (39% increase, 10 microM) and persisting at 2 h. These effects were associated with rearrangement of the EC actin cytoskeleton, early myosin light chain phosphorylation, and spatially defined (cell periphery) translocation of both Rac and cortactin. ATP (10 microM)-treated EC demonstrated a significant increase in Rac activation relative to controls, with a maximal effect (approximately 4-fold increase) at 10 min. Finally, ATP-induced barrier enhancement was markedly attenuated by reductions of either Rac or cortactin (small interfering RNA) relative to controls. Our results suggest for the first time that ATP-mediated barrier protection is associated with cytoskeletal activation and is dependent on both Rac activation and cortactin.


Bilateral Tactile Input Patterns Decoded at Comparable Levels But Different Time Scales in Neocortical Neurons.
The presence of contralateral tactile input can profoundly affect ipsilateral tactile perception, and unilateral stroke in somatosensory areas can result in bilateral tactile deficits, suggesting that bilateral tactile integration is an important part of brain function. Although previous studies have shown that bilateral tactile inputs exist and that there are neural interactions between inputs from the two sides, no previous study explored to what extent the local neuronal circuitry processing contains detailed information about the nature of the tactile input from the two sides. To address this question, we used a recently introduced approach to deliver a set of electrical, reproducible, tactile afferent, spatiotemporal activation patterns, which permits a high-resolution analysis of the neuronal decoding capacity, to the skin of the second forepaw digits of the anesthetized male rat. Surprisingly, we found that individual neurons of the primary somatosensory can decode contralateral and ipsilateral input patterns to comparable extents. Although the contralateral input was stronger and more rapidly decoded, given sufficient poststimulus processing time, ipsilateral decoding levels essentially caught up to contralateral levels. Moreover, there was a weak but significant correlation for neurons with high decoding performance for contralateral tactile input to also perform well on decoding ipsilateral input. Our findings shed new light on the brain mechanisms underlying bimanual haptic integration.SIGNIFICANCE STATEMENT Here we demonstrate that the spiking activity of single neocortical neurons in the somatosensory cortex of the rat can be used to decode patterned tactile stimuli delivered to the distal ventral skin of the second forepaw digits on both sides of the body. Even though comparable levels of decoding of the tactile input were achieved faster for contralateral input, given sufficient integration time each neuron was found to decode ipsilateral input with a comparable level of accuracy. Given that the neocortical neurons could decode ipsilateral inputs with such small differences between the patterns suggests that S1 cortex has access to very precise information about ipsilateral events. The findings shed new light on possible network mechanisms underlying bimanual haptic processing.


Phenotypic properties of transmitted founder HIV-1.
Defining the virus-host interactions responsible for HIV-1 transmission, including the phenotypic requirements of viruses capable of establishing de novo infections, could be important for AIDS vaccine development. Previous analyses have failed to identify phenotypic properties other than chemokine receptor 5 (CCR5) and CD4+ T-cell tropism that are preferentially associated with viral transmission. However, most of these studies were limited to examining envelope (Env) function in the context of pseudoviruses. Here, we generated infectious molecular clones of transmitted founder (TF; n = 27) and chronic control (CC; n = 14) viruses of subtypes B (n = 18) and C (n = 23) and compared their phenotypic properties in assays specifically designed to probe the earliest stages of HIV-1 infection. We found that TF virions were 1.7-fold more infectious (P = 0.049) and contained 1.9-fold more Env per particle (P = 0.048) compared with CC viruses. TF viruses were also captured by monocyte-derived dendritic cells 1.7-fold more efficiently (P = 0.035) and more readily transferred to CD4+ T cells (P = 0.025). In primary CD4+ T cells, TF and CC viruses replicated with comparable kinetics; however, when propagated in the presence of IFN-α, TF viruses replicated to higher titers than CC viruses. This difference was significant for subtype B (P = 0.000013) but not subtype C (P = 0.53) viruses, possibly reflecting demographic differences of the respective patient cohorts. Together, these data indicate that TF viruses are enriched for higher Env content, enhanced cell-free infectivity, improved dendritic cell interaction, and relative IFN-α resistance. These viral properties, which likely act in concert, should be considered in the development and testing of AIDS vaccines.


Doppler reconstruction of left ventricular pressure from functional mitral regurgitation: potential importance of varying orifice geometry.
To assess the left ventricular pressure pulse, in particular its time course, reconstructed from the continuous wave Doppler signal of functional mitral regurgitation using the simplified Bernoulli equation. Prospective study with simultaneously recorded high fidelity left ventricular pressure and continuous wave Doppler traces of functional mitral regurgitation, along with indirect left atrial pressure, electrocardiograms, and phonocardiograms. Tertiary referral cardiac centre. 9 patients (age 60 (17) years) were studied immediately before or 1-20 h after routine cardiac surgery. 104 cardiac cycles were analysed. There were no consistent differences between directly measured and reconstructed pressures in the time intervals from Q to + dP/dt (mean (SD) 125 (35) v 130 (35) ms and from Q to -dP/dt (389 (30) v 387 (28) ms or from Q to maximum pressure (267 (40) v 270 (40) ms, all P = NS). The time from Q to the onset of pressure rise (67 (30) v 64 (30) ms, P < 0.01) and the duration of total left ventricular systole (404 (50) v 408 (50) ms, P < 0.01) measured by the two methods were effectively identical, though the small difference was consistent enough to be statistically significant. The calculated peak pressure drop between the left ventricle and the left atrium (45-100 mm Hg) significantly underestimated left ventricular pressure (72-150 mm Hg; 70 (11) v 105 (15) mm Hg, P < 0.01) even if mean left atrial pressure (14 (4.0) mm Hg) was taken into account. Compared with those directly derived from left ventricular pressure, values of pressure measured at + dP/dt (26 (6.5) v 53 (10) mm Hg, P < 0.01) and -dP/dt (30 (8.0) v 60 (10) mm Hg, P < 0.01), and those of the rates of increase (675 (155) v 815 (155) mm Hg/s, P < 0.01) and fall (610 (145) v 845 (175) mm Hg, P < 0.01) were all significantly underestimated by Doppler. The underestimation in peak rates of pressure change could not entirely be explained by a scaling effect of absolute pressure. To investigate interrelations between the two methods throughout the cardiac cycle, reconstructed left ventricular pressure was plotted against the direct record. The plots confirmed that the reconstructed pressure was always less than directly measured pressure, the relative degree of underestimation falling as the pressure rose. This was not the effect of acceleration but probably reflects changing geometry of the regurgitant orifice. The continuous wave Doppler trace of functional mitral regurgitation is suitable for studying the timing of overall mechanical events and normalised rates of change of pressure in the left ventricle. Estimates of atrioventricular pressure drop by this method and particularly its absolute rates of change seem to be less reliable.


[IgA antibody detection and PCR as first options in the diagnosis of perinatal HIV-1 infection].
To evaluate the sensitivity and specificity of the polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA) and IgA-specific immunoblot assays as ancillary methods to diagnose human immunodeficiency virus (HIV-1) perinatal infection. A comparative study was conducted between February and October 2001 at the Human Retrovirus Research Unit of Mexico's National University. Ninety infected and 153 non-infected children were included in the study. Viral cultures were the gold standard tests. Standardized PCR for a conserved region of the gag gene and HIV-specific IgA antibody using ELISA and immunoblot were used. Statistical analysis of results was performed with SPSS 10.0. IgA ELISA sensitivity and specificity were 61.1% and 90.8%, respectively. Immunoblot had a sensitivity of 82.2% and a specificity of 95.4%. PCR had an overall sensitivity of 98.3% and a specificity of 100% with only one false negative result. If both assays were run, the sensitivity increased to 100% and the specificity to 96%. A very high sensitivity and specificity is reached when using together PCR and IgA immunoblot; these assays are useful for perinatal diagnosis of HIV-1.


Continuous-wave ultrasonic modulation of scattered laser light to image objects in turbid media.
Continuous-wave ultrasonic modulation of scattered laser light has been used to image objects in tissue-simulating turbid media for what is to our knowledge the first time. The ultrasound wave focused into the turbid media modulates the laser light passing through the ultrasonic focal zone. The modulated laser light collected by a photomultiplier tube reflects the local mechanical and optical properties in the focal zone. Buried objects are located with millimeter resolution by scanning and detecting alterations of the modulated optical signal. This technique has the potential to provide a noninvasive, nonionizing, inexpensive diagnostic tool for diseases such as breast cancer.


Levels of empathy among undergraduate physiotherapy students: A cross-sectional study at two universities in Istanbul.
The aim of this study is to determine differences of levels of empathy among undergraduates in each year of their four-year programs of physiotherapy. During the 2014-2015 academic school year, 381 physiotherapy students were enlisted from two universities in Istanbul, one a foundation and the other a government university. The Turkish version of the Jefferson Scale of Physician Empathy was administered. Students were asked to indicate interest in particular physiotherapy specialties as well as their region of origin in Turkey. The Kruskal-Wallis analysis was used to determine differences among the four study years, and also to measure relationships between specialty interest, home-region, and empathy scores of the students. Empathy scores were also compared according to gender. The difference of empathy scores between the students of the two universities was borderline significant (p=0.057). Empathy scores in both universities increased to a significant degree after school entrance and decreased in the final year. Levels of empathy did not change according to gender, specialty interest, or home-region (p=0.722, 0.524, and 0.309, respectively). This study points to the need for physiotherapy curricula that would enhance empathy and give students practice in exhibiting this valuable attribute. Additional studies are needed that would include larger study populations and track the same students year by year as to how and why their empathy levels change during their training.


Nitric oxide modulates neuropeptide Y regulation of ion transport in mouse ileum.
The possible involvement of nitric oxide in the regulation of intestinal ion transport induced by neuropeptide Y (NPY) was investigated by evaluating the effects of NG-methyl-L-arginine (L-NMA), L-arginine and S-nitroso-N-acetylpenicillamine (SNAP) on NPY activity in mouse ileum mounted in Ussing chambers in vitro. Serosal NPY (10 nM) produced a sustained decrease in basal transmural short circuit current (Isc) and potential difference without altering the tissue conductance. Pretreatment of tissues with L-arginine (3 mM), but not D-arginine (10 mM), blocked the NPY-mediated changes in Isc. This L-arginine effect on NPY activity was reversed by L-NMA (3 mM), and not by NG-methyl-D-arginine (10 mM). The L-arginine effect on NPY activity was concentration-related with an A50 (95% CL) value of 1.6 (0.9-2.3) mM. In contrast to L-arginine, L-NMA (1 mM) pretreatment of tissues produced an enhancement of NPY activity, resulting in a 3.8-fold leftward displacement of the NPY concentration-response curve; NG-methyl-D-arginine was without effect. The effect of L-NMA on NPY activity was concentration-related with an A50 (95% CL) value of 45.3 (23.2-68.8) microM. Serosal application of SNAP, a nitric oxide donor, produced a concentration-related decrease in basal Isc and potential difference without altering tissue conductance with an A50 (95% CL) value of 22.5 (11.1-40.5) microM. Pretreatment of tissue with SNAP (100 microM) reduced the NPY activity with rightward displacement of NPY concentration-response curve. Pretreatment of tissues with L-arginine also blocked the reduction of Isc by [D-Pen2, D-Pen5]enkephalin (10-30 nM), H2N-Tyr-D-Ala-Phe-Glu-Val-Val-Gly-NH2 (10-30 nM) and somatostatin (0.3-1.0 microM), but had no effect on norepinephrine (0.1-0.3 microM)-induced decrease in mouse ileal Isc. These results show that [fgc]l-arginine and SNAP block NPY-mediated changes in ion transport, suggesting that nitric oxide may play a role in the regulation of NPY-mediated ion transport in the mouse ileum.


An Acyl-Linked Dimer of Daptomycin Is Strongly Inhibited by the Bacterial Cell Wall.
The lipopeptide antibiotic daptomycin is active against Gram-positive pathogens. It permeabilizes bacterial cell membranes, which involves the formation of membrane-associated oligomers. We here studied a dimer of daptomycin whose two subunits were linked through a bivalent aliphatic acyl chain. Unexpectedly, the dimer had very low activity on vegetative Staphylococcus aureus and Bacillus subtilis cells. However, activity resembled that of monomeric daptomycin on liposomes and on B. subtilis L-forms. These findings underscore the importance of the bacterial cell wall in daptomycin resistance.


Influences on policy-formulation, decision-making, organisation and management for maternal, newborn and child health in Bangladesh, Ethiopia, Malawi and Uganda: The roles and legitimacy of a multi-country network.
The Network for Improving Quality of Care for Maternal, Newborn and Child Health (QCN) is intended to facilitate learning, action, leadership and accountability for improving quality of care in member countries. This requires legitimacy-a network's right to exert power within national contexts. This is reflected, for example, in a government's buy-in and perceived ownership of the work of the network. During 2019-2022 we conducted iterative rounds of stakeholder interviews, observations of meetings, document review, and hospital observations in Bangladesh, Ethiopia, Malawi, Uganda and at the global level. We developed a framework drawing on three models: Tallberg and Zurn which conceptualizes legitimacy of international organisations dependent on their features, the legitimation process and beliefs of audiences; Nasiritousi and Faber, which looks at legitimacy in terms of problem, purpose, procedure, and performance of institutions; Sanderink and Nasiritousi, to characterize networks in terms of political, normative and cognitive interactions. We used thematic analysis to characterize, compare and contrast institutional interactions in a cross-case synthesis to determine salient features. Political and normative interactions were favourable within and between countries and at global level since collective decisions, collaborative efforts, and commitment to QCN goals were observed at all levels. Sharing resources and common principles were not common between network countries, indicating limits of the network. Cognitive interactions-those related to information sharing and transfer of ideas-were more challenging, with the bi-directional transfer, synthesis and harmonization of concepts and methods, being largely absent among and within countries. These may be required for increasing government ownership of QCN work, the embeddedness of the network, and its legitimacy. While we find evidence supporting the legitimacy of QCN from the perspective of country governments, further work and time are required for governments to own and embed the work of QCN in routine care.


Celebrating Soft Matter's 10th Anniversary: chain configuration and rate-dependent mechanical properties in transient networks.
Numerical solution of a coupled set of Smoluchowski convection-diffusion equations of associating polymers modelled as finitely extensible dumbbells enables computation of time-dependent end-to-end distributions for bridged, dangling, and looped chains in three dimensions as a function of associating end-group kinetics. Non-monotonic flow curves which can lead to flow instabilities during shear flow result at low equilibrium constant and high association rate from two complementary phenomena: a decrease in the fraction of elastically active chains with increasing shear rate and non-monotonic extension in the population of elastically active chains. Chain tumbling leads to reformation of bridges, resulting in an increased fraction of bridged chains at high Deborah number and significant reduction in the average bridge chain extension. In the start-up of steady shear, force-activated chain dissociation and chain tumbling cause both stress overshoot and stress ringing behaviour prior to reaching steady state stress values. During stress relaxation following steady shear, chain kinetics and extension mediate both the number of relaxations and the length of time required for system relaxation. While at low association rate relaxation is limited by the relaxation of dangling chains and the rate of dangling chain formation, at high association rate coupling of dangling and bridged chains leads to simultaneous relaxation of all chains due to a dynamic equilibrium between dangling and bridged states.


A longitudinal assessment of the associations among response access, attention problems, and aggression during childhood.
Children with ADHD symptoms often display social competence deficits, yet mechanisms for their social difficulties remain unclear. Using data from the normative sample of non-intervention respondents (N = 387; 50 % male; 49 % non-European-American; age at initial assessment: M = 6.5 years, SD = 0.48) in the Fast Track project (Lochman and CPPRG Journal of Consulting and Clinical Psychology 63:549-59, 1995), the social-information processing ability of accessing responses for social situations was modeled across four time points from kindergarten to third grade. Teacher-rated aggression and ADHD symptoms were included as predictors of the intercept and slope. Low ADHD symptoms were associated with a decline in aggressive responses across childhood, whereas high ADHD symptoms were linked to an increase in aggressive responses that decelerated between second and third grade. Regarding competent responses, low ADHD symptoms predicted increases in competent responses, but this increase decelerated between second and third grade. High ADHD symptoms were also associated with a slight increase in competent responses into first grade, but competent responses decreased from first to third grade. Neither aggression nor the interaction of ADHD symptoms and aggression accounted for a significant amount of variance in aggressive or competent responses. Future research should identify if differences in response access associated with high and low ADHD symptoms link to difficulties making and keeping friendships.


Wavefront propagation from one plane to another with the use of Zernike polynomials and Taylor monomials.
In wavefront-driven vision correction, ocular aberrations are often measured on the pupil plane and the correction is applied on a different plane. The problem with this practice is that any changes undergone by the wavefront as it propagates between planes are not currently included in devising customized vision correction. With some valid approximations, we have developed an analytical foundation based on geometric optics in which Zernike polynomials are used to characterize the propagation of the wavefront from one plane to another. Both the boundary and the magnitude of the wavefront change after the propagation. Taylor monomials were used to realize the propagation because of their simple form for this purpose. The method we developed to identify changes in low-order aberrations was verified with the classical vertex correction formula. The method we developed to identify changes in high-order aberrations was verified with ZEMAX ray-tracing software. Although the method may not be valid for highly irregular wavefronts and it was only proven for wavefronts with low-order or high-order aberrations, our analysis showed that changes in the propagating wavefront are significant and should, therefore, be included in calculating vision correction. This new approach could be of major significance in calculating wavefront-driven vision correction whether by refractive surgery, contact lenses, intraocular lenses, or spectacles.


Ultrasound imaging of dorsal neck muscles with speckle tracking analyses - the relationship between muscle deformation and force.
The development of methods of non-invasive measurement of neck muscle function remains a priority in the clinical sciences. In this study, dorsal neck muscle deformation vs time curves (deformation area) were evaluated against incremental force, recorded from non-invasive real-time ultrasound measurement. The results revealed subject-specific moderate to strong linear or non-linear relationships between deformation and force. Test-retest variability showed strong reliability for all five neck muscles summed together and fair to good reliability for the five muscles evaluated separately. Multivariate statistics were used to analyse the interactions between the dorsal neck muscles during different percentages of maximal voluntary contraction (MVC). Low force (10-20% MVC) was related to muscle shortening; higher force (40-80% MVC) showed combination of shortening and elongation deformation in the muscle interactions. The muscle interactions during isometric MVC test were subject-specific, with different combinations and deformations of the five neck muscles. Force ≥40% MVC were associated with a forward movement of the cervical spine that affected the ultrasound measurement of the dorsal neck muscles. Ultrasound with speckle-tracking analyses may be best used to detect low levels (<40% MVC) of neck muscle activity.


Why people attend science festivals: Interests, motivations and self-reported benefits of public engagement with research.
As a form of public engagement, science festivals have rapidly expanded in size and number over recent years. However, as with other domains of informal public engagement that are not linked to policy outcomes, existing research .does not fully address science festivals' impacts and popularity. This study adduces evidence from surveys and focus groups to elucidate the perspectives of visitors at a large UK science festival. Results show that visitors value the opportunities afforded by the science festival to interact with scientific researchers and to encounter different types of science engagement aimed at adults, children and families. The most significant self-reported impact of attending a science festival is the development of increased interest in and curiosity about new areas of scientific knowledge within a socially stimulating and enjoyable setting.


The decrease of cardiac chamber volumes and output during positive-pressure ventilation.
Positive-pressure ventilation (PPV) is widely used for treatment of acute cardiorespiratory failure, occasionally at the expense of compromised cardiac function and arterial blood pressure. The explanation why has largely rested on interpretation of intracardiac pressure changes. We evaluated the effect of PPV on the central circulation by studying cardiac chamber volumes with cardiac magnetic resonance imaging (CMR). We hypothesized that PPV lowers cardiac output (CO) mainly via the Frank-Starling relationship. In 18 healthy volunteers, cardiac chamber volumes and flow in aorta and the pulmonary artery were measured by CMR during PPV levels of 0, 10, and 20 cmH2O applied via a respirator and a face mask. All cardiac chamber volumes decreased in proportion to the level of PPV. Following 20-cmH2O PPV, the total diastolic and systolic cardiac volumes (±SE) decreased from 605 (±29) ml to 446 (±29) ml (P < 0.001) and from 265 (±17) ml to 212 (±16) ml (P < 0.001). Left ventricular stroke volume decreased by 27 (±4) ml/beat; heart rate increased by 7 (±2) beats/min; and CO decreased by 1.0 (±0.4) l/min (P < 0.001). From 0 to 20 cmH2O, right and left ventricular peak filling rates decreased by -146 (±32) and -187 (±64) ml/s (P < 0.05) but maximal emptying rates were unchanged. Cardiac filling and output decrease with increasing PPV in healthy volunteers. The decrease is seen even at low levels of PPV and should be taken into account when submitting patients to mechanical ventilation with positive pressures. The decrease in CO is fully explained by the Frank-Starling mechanism.


The Mayo Clinic cohort study of personality and aging: design and sampling, reliability and validity of instruments, and baseline description.
We established a historical cohort of 7,216 subjects who completed the Minnesota Multiphasic Personality Inventory (MMPI) at the Mayo Clinic from 1962 through 1965 for research (not clinical indication), and who resided within a 120-mile radius centered in Rochester, Minnesota. We describe here the overall cohort design and sampling, we report results concerning reliability and validity, and we describe age and sex patterns at baseline for four MMPI scores of primary interest (depression, anxiety, social introversion, and negativity). Subjects excluded from the cohort because of missing data had MMPI scores similar to subjects included (after appropriate rescaling). A cut-off specific for age and sex at the 75th percentile of the distribution of raw scores was valid compared with the traditional clinical cut-off (T scores plus one standard deviation). Baseline scores for all four scales were higher in women than in men at all ages (all p < 0.0001). Depression and social introversion scores showed an increasing trend with age in both sexes (Spearman rank correlation, rho = 0.05 and 0.08, respectively, p < 0.0001 for both). Baseline scores on the anxiety scale showed a decreasing trend with age in both sexes (rho = -0.06, p < 0.0001). Negativity scores remained relatively stable with age in both sexes (rho = 0.03, p = 0.01). We found a high correlation between the anxiety score and the negativity score (rho = 0.90, p < 0.0001) even after the exclusion of overlapping items (rho = 0.68, p < 0.0001). This newly established historical cohort study provides opportunities to test hypotheses regarding the link between personality and aging, aging-related diseases, and overall mortality.


Contrasting epigenetic states of heterochromatin in the different types of mouse pluripotent stem cells.
Mouse embryonic stem cells (ESCs) and epiblast stem cells (EpiSCs) represent naive and primed pluripotency states, respectively, and are maintained in vitro by specific signalling pathways. Furthermore, ESCs cultured in serum-free medium with two kinase inhibitors (2i-ESCs) are thought to be the ground naïve pluripotent state. Here, we present a comparative study of the epigenetic and transcriptional states of pericentromeric heterochromatin satellite sequences found in these pluripotent states. We show that 2i-ESCs are distinguished from other pluripotent cells by a prominent enrichment in H3K27me3 and low levels of DNA methylation at pericentromeric heterochromatin. In contrast, serum-containing ESCs exhibit higher levels of major satellite repeat transcription, which is lower in 2i-ESCs and even more repressed in primed EpiSCs. Removal of either DNA methylation or H3K9me3 at PCH in 2i-ESCs leads to enhanced deposition of H3K27me3 with few changes in satellite transcript levels. In contrast, their removal in EpiSCs does not lead to deposition of H3K27me3 but rather removes transcriptional repression. Altogether, our data show that the epigenetic state of PCH is modified during transition from naive to primed pluripotency states towards a more repressive state, which tightly represses the transcription of satellite repeats.


Estimating the impact of pictorial health warnings and "plain" cigarette packaging: evidence from experimental auctions among adult smokers in the United States.
To estimate differences in demand for cigarette packages with different packaging and health warning label formats. Adult smokers (n=404) in four states participated in experimental auctions. Participants bid on two of four experimental conditions, each involving a different health warning label format but with the same warning message: (1) text on 50% of pack side; (2) text on 50% of the pack front and back; (3) text with a graphic picture on 50% of the pack front and back; and (4) same as previous format, but without brand imagery. Mean bids decreased across conditions (1: $3.52; 2: $3.43; 3: $3.11; 4: $2.93). Bivariate and multivariate random effects models indicated that there was no statistically significant difference in demand for packs with either of the two text only warnings; however, demand was significantly lower for both packs with prominent pictorial warnings, with the lowest demand associated with the plain, unbranded pack. Results suggest that prominent health warnings with graphic pictures will reduce demand for cigarettes. Regulators should not only consider this type of warning label, but also plain packaging policies for tobacco products.


Significance of pleural effusion in neuroblastoma.
Pleural effusion is uncommon at diagnosis of neuroblastoma in children. Because the presence of malignant cells in pleural fluid may significantly change the management and outcome of patients with neuroblastoma, we retrospectively analyzed a cohort of neuroblastoma patients who presented with pleural effusion at the time of diagnosis to determine the incidence, presentation, stage, treatment, and outcome of these patients. We reviewed the presenting features of 295 patients with the diagnosis of neuroblastoma who received treatment at St. Jude Children's Research Hospital between 1991 and 2005. Patients were chosen for further analysis if pleural effusion had been identified on chest radiographs or computed tomography (CT) scans at diagnosis Thirty-one out of 295(10.5%) patients with neuroblastoma had pleural effusion identified at time of presentation. International neuroblastoma staging system (INSS) risk stratification was high risk in 29 cases and intermediate risk and low risk in 1 case each. The primary site of disease was abdomen in 26 patients; mediastinum in 5. We conducted cytologic analysis of pleural fluid of nine patients; the specimen of seven contained malignant cells. Eighteen of 31 patients died of progressive or recurrent disease. In patients with neuroblastoma, pleural effusion is usually associated with unfavorable biologic features and high-risk disease. Pleural fluid should be examined cytologically and at a time when the results would change the risk stratification. There was no statistically significant difference in the survival rate of the patients with high-risk neuroblastoma with or without malignant pleural effusion.


Relationship of mood disorders to violence.
Past research on the relationship between mood disorders and violent behavior has been inconsistent, sometimes finding a relationship between the two and sometimes finding no relationship. Any relationship is arguably complex, and this area of research would benefit from attempts to clarify the relationship. This paper addresses the issue of complexity by examining the relationship between specific mood disorder categories and symptoms and six conceptually different indicators of violent behavior. Relationships are analyzed in logistic regression models where demographic and problem drinking variables are included to control variation that may be accounted for by these factors. The study uses a sample of 1140 recently incarcerated male felons. Psychiatric disorder diagnoses are based on the Diagnostic Interview Schedule. There is evidence of a direct relationship between a lifetime diagnosis of dysthymia and an arrest or incarceration history for robbery as well as with multiple incidents of fighting since age 18. Recurrent depression was significantly associated with a robbery incarceration history. Depression symptoms (regardless of whether a disorder diagnosis was made) were associated with multiple incidents of fighting since age 18. Manic symptoms were inconsistently associated with "expressive" violence and a number of mood disorder/violence models showed no significant relationship between the two.


Cis-Golgi cisternal assembly and biosynthetic activation occur sequentially in plants and algae.
The cisternal progression/maturation model of Golgi trafficking predicts that cis-Golgi cisternae are formed de novo on the cis-side of the Golgi. Here we describe structural and functional intermediates of the cis cisterna assembly process in high-pressure frozen algae (Scherffelia dubia, Chlamydomonas reinhardtii) and plants (Arabidopsis thaliana, Dionaea muscipula; Venus flytrap) as determined by electron microscopy, electron tomography and immuno-electron microscopy techniques. Our findings are as follows: (i) The cis-most (C1) Golgi cisternae are generated de novo from cisterna initiators produced by the fusion of 3-5 COPII vesicles in contact with a C2 cis cisterna. (ii) COPII vesicles fuel the growth of the initiators, which then merge into a coherent C1 cisterna. (iii) When a C1 cisterna nucleates its first cisterna initiator it becomes a C2 cisterna. (iv) C2-Cn cis cisternae grow through COPII vesicle fusion. (v) ER-resident proteins are recycled from cis cisternae to the ER via COPIa-type vesicles. (vi) In S. dubia the C2 cisternae are capable of mediating the self-assembly of scale protein complexes. (vii) In plants, ∼90% of native α-mannosidase I localizes to medial Golgi cisternae. (viii) Biochemical activation of cis cisternae appears to coincide with their conversion to medial cisternae via recycling of medial cisterna enzymes. We propose how the different cis cisterna assembly intermediates of plants and algae may actually be related to those present in the ERGIC and in the pre-cis Golgi cisterna layer in mammalian cells.


Access roads impact enzyme activities in boreal forested peatlands.
We investigated the impacts of resource access roads on soil enzyme activities in contrasting forested boreal peatlands (bog and fen). In August 2016, a total of 72 peat samples were collected from twelve 20 m long transects perpendicular to access roads, with a further six samples collected from undisturbed reference areas. Sampling locations represent a range in three variables associated with roads: 1) side of the road (upstream/downstream), 2) distance to a culvert (longitudinal; <2 and >20 m), and 3) distance from the road (lateral; 2, 6, and 20 m). Phenol oxidase and hydrolase (glucosidase, sulfatase, xylosidase, glucosaminidase, and phosphatase) enzyme activities were determined for each sample, in addition to water table depth, phenolic concentration, pH, and peat temperature. The average hydrolase activities in the fen were ~four times higher than in the bog. At the bog, the water table depth, phenolic concentration, pH and the activities of phenol oxidase, sulfatase, glucosidase, xylosidase and glucosaminidase were all significantly influenced by one or more road associated factors. The highest enzyme activities in the bog occurred on the downstream side of the road at plots located far from the culvert. In contrast, the flow of water in the fen was not perpendicular to the road. Consequently, no significant variations in water table depth, phenolic concentration, pH or enzyme activity were found with respect to road associated factors. Results indicate that road crossings in boreal peatlands can indirectly alter enzyme activities, likely as part of a causal chain following changes to hydrology and redox conditions. Two of six investigated enzymes had significantly higher activities in the road disturbed areas compared to undisturbed areas, suggesting ultimately that roads may enhance organic matter decomposition rates. However, adequate hydrologic connections through culverts and road construction parallel to the water flow can minimize the road-induced impacts.


Endoscopic resection of a giant intradural retroclival ecchordosis physaliphora: surgical technique and literature review.
To report the first complete resection of a giant ecchordosis physaliphora using an endoscopic transclival approach and to provide a current review of the literature. This rare benign lesion, originating from embryonic notochordal remnants, was located in the prepontine cistern of a 63-year-old man presenting with progressive tremor and imbalance. Preoperative imaging demonstrated a 2.1-cm intradural lesion abutting the pons and basilar artery and extending through the dura mater. A gross total resection was successfully achieved endoscopically without neurovascular compromise or additional complications. Postoperative histopathologic examination was consistent with a diagnosis of giant ecchordosis physaliphora. An endoscopic endonasal transclival approach provided a direct, minimally invasive route for safe and complete resection of this rare prepontine tumor, as it has for similarly located skull base chordomas. Our experience highlights the utility of endoscopy in visualization of both pathologic entities and nearby critical neurovascular structures in the management of ecchordosis physaliphora and other cranial base neoplasms.


Nanoscale structure of Si/SiO2/organics interfaces.
X-ray reflectivity measurements of increasingly more complex interfaces involving silicon (001) substrates reveal the existence of a thin low-density layer intruding between the single-crystalline silicon and the amorphous native SiO2 terminating it. The importance of accounting for this layer in modeling silicon/liquid interfaces and silicon-supported monolayers is demonstrated by comparing fits of the measured reflectivity curves by models including and excluding this layer. The inclusion of this layer, with 6-8 missing electrons per silicon unit cell area, consistent with one missing oxygen atom whose bonds remain hydrogen passivated, is found to be particularly important for an accurate and high-resolution determination of the surface normal density profile from reflectivities spanning extended momentum transfer ranges, now measurable at modern third-generation synchrotron sources.


Soluble and membrane-bound pyroglutamyl-peptidase I activity in the developing cerebellum and brain cortex.
Developmental changes of soluble and particulate pyroglutamyl (pGlu)-peptidase I activities in the rat brain cortex and in the cerebellum are described in this work. The enzyme activity has been measured spectrofluorimetrically using pGlu-b-naphthylamide as substrate (in the presence and absence of EDTA and DTT, necessary activators of the enzyme) in both soluble and particulate fractions. In the soluble fraction of the cerebellum and brain cortex, pGlu-peptidase I activity is high in the perinatal period and decreases two or three folds subsequently, at a later stage in the cerebellum than in the brain cortex, reaching adult levels at the end of the first postnatal month. The decrease in the activity of pGlu-peptidase observed in this work coincides with increasing levels of brain thyroliberin concentration after the second postnatal week. The particulate pGlu-peptidase I activity, obtained after osmotic shock and high-salt treatment, shows less significant changes during brain development in the areas under study. It is suggested that cytosolic pGlu-peptidase I could play a part in the normal development of the rat central nervous system.


Electrochemical evaluation methods of vanadium flow battery electrodes.
Various testing methods, such as cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS), have been employed to evaluate the electrode performance of vanadium flow batteries (VFB). Due to the variations in the testing devices and characterization parameters in the literature, a number of reported results are incomparable and even sometimes contradictory. In this report, a reliable device is proposed for the electrochemical characterization of electrode materials, and the parameter selection was demonstrated to be critical for achieving reliable evaluation and reducing the effects of side reactions. As for the structure of the graphite felt electrode, volume current density is proposed to replace the area current density as the main evaluation indicator. Furthermore, the effect of side reactions is discussed and the upper limit voltage of 1.60 V is found to be suitable in the charge process of VFB since selecting this value can greatly protect the active sites on the electrode and avoid the capacity fading caused by side reactions.


The Turkish version of the Physical Activity Scale for the Elderly (PASE): its cultural adaptation, validation, and reliability.
This study aimed to describe the cultural adaptation of the Turkish Physical Activity Scale for the Elderly (PASE) and to examine the reliability and validity of the scale in older Turkish adults. Eighty elderly people were recruited for the study. The assessments included the PASE, the International Physical Activity Questionnaire (IPAQ), the Short Physical Performance Battery and Short Form-36 Quality of Life Questionnaire (SF-36), and the Mini Mental State Test. Outcome measures were conducted twice within a week (test-retest) for reliability. Cronbach's α coefficient was 0.714 for the initial evaluation. The intraclass correlation coefficient for the test-retest reliability was 0.995 with a 95% confidence interval of 0.993-0.997. A high level of positive correlation (0.742, P < 0.001) was found between the total score of PASE and the total scores of IPAQ. There were strong positive correlations between the PASE and the total score of SPPB (0.622, P < 0.001), while an average level of positive correlation with SF-36 was found (0.432, P < 0.001). The results of the study suggest that the Turkish version of the PASE has powerful measurement qualities, which makes it a reliable and valid scale for the fields of research and practice.


Use-dependent AMPA receptor block reveals segregation of spontaneous and evoked glutamatergic neurotransmission.
Earlier findings had suggested that spontaneous and evoked glutamate release activates non-overlapping populations of NMDA receptors. Here, we evaluated whether AMPA receptor populations activated by spontaneous and evoked release show a similar segregation. To track the receptors involved in spontaneous or evoked neurotransmission, we used a polyamine agent, philanthotoxin, that selectively blocks AMPA receptors lacking GluR2 subunits in a use-dependent manner. In hippocampal neurons obtained from GluR2-deficient mice, philanthotoxin application decreased AMPA-receptor-mediated spontaneous miniature EPSCs (AMPA-mEPSCs) down to 20% of their initial level within 5 min. In contrast, the same philanthotoxin application at rest decreased the subsequent AMPA-receptor-mediated evoked EPSCs (eEPSCs) only down to 80% of their initial value. A 10-min-long perfusion of philanthotoxin further decreased AMPA-eEPSC amplitudes to 60% of their initial magnitude, which remained substantially higher than the level of AMPA-mEPSC block achieved within 5 min. Finally, stimulation after removal of philanthotoxin resulted in reversal of AMPA-eEPSC block, verifying strict use dependence of philanthotoxin. These results support the notion that spontaneous and evoked neurotransmission activate distinct sets of AMPA receptors and bolster the hypothesis that synapses harbor separate microdomains of evoked and spontaneous signaling.


Protection against experimental Bordetella bronchiseptica infection in mice by active immunization with killed vaccine.
Mice immunized with a killed vaccine of phase I Bordetella bronchiseptica were challenged with various numbers of virulent B. bronchiseptica by intraperitoneal, intracerebral, or intranasal routes. The course of infection was compared among these routes, and the protective effect of vaccination was quantitatively analyzed. In ddN mice infected intraperitoneally with 1.8 X 10(8) cells (ca. 80 times the 50% lethal dose [LD50]) the organisms rapidly increased in the intraperitoneal fluid, spleen, and liver within few days and caused splenic atrophy, septicemia, and death. However, immunizations with 5 X 10(9) cells gave the mice a high agglutinin titer and suppressed the increase in the number of organisms. With four immunizations, the lungs and livers were clear within 3 days, and with one or two immunizations, they were clear within 7 days. These immunizations effectively protected the mice from death but did not protect them from splenic atrophy. In the intracerebral infection with 1.4 X 10(6) cells (ca. 1.2 X 10(5) LD50), the number of organisms rapidly increased in the brain and caused encephalitis, splenic atrophy, and death. However, four or five immunizations completely suppressed the increase in the brain and protected the mice from death and splenic atrophy. After intranasal infection with 4 X 10(6) cells (ca. 25 LD50), the organisms rapidly increased in the nasal cavity and lungs and caused pneumonia and death. Immunization with 5 X 10(9) cells was effective in clearing the organisms from the lungs and in protecting against death and splenic atrophy. However, the organisms were not cleared from the nasal cavity for 60 to 150 days after the challenge with as little as 10(2) cells, even in the mice with an agglutinin titer as high as 1:10,000.


Monitoring long-lasting insecticidal net (LLIN) durability to validate net serviceable life assumptions, in Rwanda.
To validate assumptions about the length of the distribution-replacement cycle for long-lasting insecticidal nets (LLINs) in Rwanda, the Malaria and other Parasitic Diseases Division, Rwanda Ministry of Health, used World Health Organization methods to independently confirm the three-year LLIN serviceable life span recommendation of WHO. Approximately 3,000 coded LLINs, distributed as part of a national campaign, were monitored in six sites, by means of six-monthly visits to selected houses. Two indicators, survivorship/attrition, a measure of the number of nets remaining, and fabric integrity, the proportion of remaining nets in either 'good', 'serviceable' or 'needs replacement' condition, based on holes in the net material, were tracked. To validate the assumption that the intervention would remain effective for three years, LLIN coverage, calculated using either survivorship, or integrity, by removing nets in the 'needs replacement' category from the survivorship total, was compared with the predicted proportion of nets remaining, derived from a net loss model, that assumes an LLIN serviceable life of three years. After two years, there was close agreement between estimated LLIN survivorship at all sites, 75% (range 64-84%), and the predicted proportion of nets remaining, 75%. However, when integrity was considered, observed survivorship at all sites, declined to 42% (range 10-54%). More than half, 58%, of the LLINs fell into the 'needs replacement' category after two years. While these nets were counted for survivorship, they were judged to be of little-to-no benefit to a user. Therefore, when integrity was taken into account, survivorship was significantly lower than predicted, suggesting that net serviceable life was actually closer to two, rather than three years, and, by extension, that the impact of the intervention during year three of the LLIN distribution-replacement cycle could be well below that seen in years one and two.


Far-field super-resolution imaging of resonant multiples.
We demonstrate for the first time that seismic resonant multiples, usually considered as noise, can be used for super-resolution imaging in the far-field region of sources and receivers. Tests with both synthetic data and field data show that resonant multiples can image reflector boundaries with resolutions more than twice the classical resolution limit. Resolution increases with the order of the resonant multiples. This procedure has important applications in earthquake and exploration seismology, radar, sonar, LIDAR (light detection and ranging), and ultrasound imaging, where the multiples can be used to make high-resolution images.


Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf.
Specific adaptors regulate the activation of initiator caspases; for example, FADD and Apaf-1 engage caspases 8 and 9, respectively. The adaptors ASC, Ipaf and RIP2 have each been proposed to regulate caspase-1 (also called interleukin (IL)-1 converting enzyme), which is activated within the 'inflammasome', a complex comprising several adaptors. Here we show the impact of ASC-, Ipaf- or RIP2-deficiency on inflammasome function. ASC was essential for extracellular ATP-driven activation of caspase-1 in toll-like receptor (TLR)-stimulated macrophages. Accordingly, ASC-deficient macrophages exhibited defective maturation of IL-1beta and IL-18, and ASC-null mice were resistant to lipopolysaccharide-induced endotoxic shock. Furthermore, activation of caspase-1 in response to an intracellular pathogen (Salmonella typhimurium) was abrogated severely in ASC-null macrophages. Unexpectedly, Ipaf-deficient macrophages activated caspase-1 in response to TLR plus ATP stimulation but not S. typhimurium. Caspase-1 activation was not compromised by loss of RIP2. These data show that whereas ASC is key to caspase-1 activation within the inflammasome, Ipaf provides a special conduit to the inflammasome for signals triggered by intracellular pathogens. Notably, cell death triggered by stimuli that engage caspase-1 was ablated in macrophages lacking either ASC or Ipaf, suggesting a coupling between the inflammatory and cell death pathways.


Very low inadequate dietary intakes of essential n-3 polyunsaturated fatty acids (PUFA) in pregnant and lactating French women: The INCA2 survey.
The French National survey INCA2 pointed out that the majority of the French population (children, adolescents, adults and elderly) ingest low quantities of n-3 polyunsaturated fatty acid (PUFA) in the form of both precursor (alpha-linolenic acid, ALA) and long-chain (mainly docosahexaenoic acid, DHA). However, we don't know whether such inadequate n-3 PUFA consumption is also found again in pregnant and lactating women. Dietary lipid and PUFA intakes were determined from 28 pregnant and 21 lactating French women by using the most recent set of national robust data on food (National Survey INCA2 performed in 2006 and 2007), and compared with that of 742 women of childbearing age. Main results showed that mean daily intakes of n-3 PUFA were very low in this French woman population because no pregnant and lactating women met recommended dietary intakes (RDIs). Moreover, some of them ingested quantities 4 times (ALA) to 10 times (DHA) lower than RDIs. Very similar dietary intakes were observed in women of childbearing age. French pregnant and lactating women did not change their dietary habits to favor ALA and n-3 long-chain PUFA consumption via rich-ALA vegetable oils and fish and oily fish consumption, and have low n-3 PUFA dietary consumption typical of French women of childbearing age. Such PUFA intakes could have adverse impact on long-chain n-3 PUFA incorporation in brain membranes of fetus and infants, but also on cognitive and visual development of infants during the first years of life.


Antifibrotic Effects of High-Mobility Group Box 1 Protein Inhibitor (Glycyrrhizin) on Keloid Fibroblasts and Keloid Spheroids through Reduction of Autophagy and Induction of Apoptosis.
Overabundance of extracellular matrix resulting from hyperproliferation of keloid fibroblasts (KFs) and dysregulation of apoptosis represents the main pathophysiology underlying keloids. High-mobility group box 1 (HMGB1) plays important roles in the regulation of cellular death. Suppression of HMGB1 inhibits autophagy while increasing apoptosis. Suppression of HMGB1 with glycyrrhizin has therapeutic benefits in fibrotic diseases. In this study, we explored the possible involvement of autophagy and HMGB1 as a cell death regulator in keloid pathogenesis. We have highlighted the potential utility of glycyrrhizin as an antifibrotic agent via regulation of the aberrant balance between autophagy and apoptosis in keloids. Higher HMGB1 expression and enhanced autophagy were observed in keloids. The proliferation of KFs was decreased following glycyrrhizin treatment. While apoptosis was enhanced in keloids after glycyrrhizin treatment, autophagy was significantly reduced. The expressions of ERK1/2, Akt, and NF-κB, were enhanced in HMGB1-teated fibroblasts, but decreased following glycyrrhizin treatment. The expression of extracellular matrix (ECM) components was reduced in glycyrrhizin-treated keloids. TGF-β, Smad2/3, ERK1/2, and HMGB1 were decreased in glycyrrhizin-treated keloids. Treatment with the autophagy inhibitor 3-MA resulted in a decrease of autophagy markers and collagen in the TGF-β-treated fibroblasts. The results indicated that autophagy plays an important role in the pathogenesis of keloids. Because glycyrrhizin appears to reduce ECM and downregulate autophagy in keloids, its potential use for treatment of keloids is indicated.


End-damage-specific proteins facilitate recruitment or stability of X-ray cross-complementing protein 1 at the sites of DNA single-strand break repair.
Ionizing radiation, oxidative stress and endogenous DNA-damage processing can result in a variety of single-strand breaks with modified 5' and/or 3' ends. These are thought to be one of the most persistent forms of DNA damage and may threaten cell survival. This study addresses the mechanism involved in recognition and processing of DNA strand breaks containing modified 3' ends. Using a DNA-protein cross-linking assay, we followed the proteins involved in the repair of oligonucleotide duplexes containing strand breaks with a phosphate or phosphoglycolate group at the 3' end. We found that, in human whole cell extracts, end-damage-specific proteins (apurinic/apyrimidinic endonuclease 1 and polynucleotide kinase in the case of 3' ends containing phosphoglycolate and phosphate, respectively) which recognize and process 3'-end-modified DNA strand breaks are required for efficient recruitment of X-ray cross-complementing protein 1-DNA ligase IIIalpha heterodimer to the sites of DNA repair.


Resistance to Leishmania major induced by tolerance to a single antigen.
In mice, susceptibility to Leishmania major is associated with the early expansion of T helper 2 cells (TH2) cells, but nothing is known of the specificity of these cells. A previously identified antigen, Leishmania homolog of receptors for activated C kinase (LACK), was found to be the focus of this initial response. Mice made tolerant to LACK by the transgenic expression of the antigen in the thymus exhibited both a diminished TH2 response and a healing phenotype. Thus, T cells that are activated early and are reactive to a single antigen play a pivotal role in directing the immune response to the entire parasite.


Triazole linker-based trivalent sialic acid inhibitors of adenovirus type 37 infection of human corneal epithelial cells.
Adenovirus type 37 (Ad37) is one of the principal agents responsible for epidemic keratoconjunctivitis (EKC), a severe ocular infection that remains without any available treatment. Recently, a trivalent sialic acid derivative (ME0322, Angew. Chem. Int. Ed., 2011, 50, 6519) was shown to function as a highly potent inhibitor of Ad37, efficiently preventing the attachment of the virion to the host cells and subsequent infection. Here, new trivalent sialic acid derivatives were designed, synthesized and their inhibitory properties against Ad37 infection of the human corneal epithelial cells were investigated. In comparison to ME0322, the best compound (17a) was found to be over three orders of magnitude more potent in a cell-attachment assay (IC50 = 1.4 nM) and about 140 times more potent in a cell-infection assay (IC50 = 2.9 nM). X-ray crystallographic analysis demonstrated a trivalent binding mode of all compounds to the Ad37 fiber knob. For the most potent compound ophthalmic toxicity in rabbits was investigated and it was concluded that repeated eye administration did not cause any adverse effects.


Dynamics of keratin assembly: exogenous type I keratin rapidly associates with type II keratin in vivo.
Keratin intermediate filaments (IF) are obligate heteropolymers containing equal amounts of type I and type II keratin. We have previously shown that microinjected biotinylated type I keratin is rapidly incorporated into endogenous bundles of keratin IF (tonofilaments) of PtK2 cells. In this study we show that the earliest steps in the assembly of keratin subunits into tonofilaments involve the extremely rapid formation of discrete aggregates of microinjected keratin. These are seen as fluorescent spots containing both type I and type II keratins within 1 min post-injection as determined by double label immunofluorescence. These observations suggest that endogenous type II keratin subunits can be rapidly mobilized from their endogenous state to form complexes with the injected type I protein. Furthermore, confocal microscopy and immunogold electron microscopy suggest that the type I-type II keratin spots from in close association with the endogenous keratin IF network. When the biotinylated protein is injected at concentrations of 0.3-0.5 mg/ml, the organization of the endogenous network of tonofilaments remains undisturbed during incorporation into tonofilaments. However, microinjection of 1.5-2.0 mg/ml of biotinylated type I results in significant alterations in the organization and assembly state of the endogenous keratin IF network soon after microinjection. The results of this study are consistent with the existence of a state of equilibrium between keratin subunits and polymerized keratin IF in epithelial cells, and provide further proof that IF are dynamic elements of the cytoskeleton of mammalian cells.


Temperate Bacteriophages from Chronic Pseudomonas aeruginosa Lung Infections Show Disease-Specific Changes in Host Range and Modulate Antimicrobial Susceptibility.
Temperate bacteriophages are a common feature of Pseudomonas aeruginosa genomes, but their role in chronic lung infections is poorly understood. This study was designed to identify the diverse communities of mobile P. aeruginosa phages by employing novel metagenomic methods, to determine cross infectivity, and to demonstrate the influence of phage infection on antimicrobial susceptibility. Mixed temperate phage populations were chemically mobilized from individual P. aeruginosa, isolated from patients with cystic fibrosis (CF) or bronchiectasis (BR). The infectivity phenotype of each temperate phage lysate was evaluated by performing a cross-infection screen against all bacterial isolates and tested for associations with clinical variables. We utilized metagenomic sequencing data generated for each phage lysate and developed a novel bioinformatic approach allowing resolution of individual temperate phage genomes. Finally, we used a subset of the temperate phages to infect P. aeruginosa PAO1 and tested the resulting lysogens for their susceptibility to antibiotics. Here, we resolved 105 temperate phage genomes from 94 lysates that phylogenetically clustered into 8 groups. We observed disease-specific phage infectivity profiles and found that phages induced from bacteria isolated from more advanced disease infected broader ranges of P. aeruginosa isolates. Importantly, when infecting PAO1 in vitro with 20 different phages, 8 influenced antimicrobial susceptibility. This study shows that P. aeruginosa isolated from CF and BR patients harbors diverse communities of inducible phages, with hierarchical infectivity profiles that relate to the progression of the disease. Temperate phage infection altered the antimicrobial susceptibility of PAO1 at subinhibitory concentrations of antibiotics, suggesting they may be precursory to antimicrobial resistance.IMPORTANCE Pseudomonas aeruginosa is a key opportunistic respiratory pathogen in patients with cystic fibrosis and non-cystic fibrosis bronchiectasis. The genomes of these pathogens are enriched with mobile genetic elements including diverse temperate phages. While the temperate phages of the Liverpool epidemic strain have been shown to be active in the human lung and enhance fitness in a rat lung infection model, little is known about their mobilization more broadly across P. aeruginosa in chronic respiratory infection. Using a novel metagenomic approach, we identified eight groups of temperate phages that were mobilized from 94 clinical P. aeruginosa isolates. Temperate phages from P. aeruginosa isolated from more advanced disease showed high infectivity rates across a wide range of P. aeruginosa genotypes. Furthermore, we showed that multiple phages altered the susceptibility of PAO1 to antibiotics at subinhibitory concentrations.


Pharmacokinetic modeling of P-glycoprotein function at the rat and human blood-brain barriers studied with (R)-[11C]verapamil positron emission tomography.
This study investigated the influence of P-glycoprotein (P-gp) inhibitor tariquidar on the pharmacokinetics of P-gp substrate radiotracer (R)-[11C]verapamil in plasma and brain of rats and humans by means of positron emission tomography (PET). Data obtained from a preclinical and clinical study, in which paired (R)-[11C]verapamil PET scans were performed before, during, and after tariquidar administration, were analyzed using nonlinear mixed effects (NLME) modeling. Administration of tariquidar was included as a covariate on the influx and efflux parameters (Qin and Qout) in order to investigate if tariquidar increased influx or decreased outflux of radiotracer across the blood-brain barrier (BBB). Additionally, the influence of pilocarpine-induced status epilepticus (SE) was tested on all model parameters, and the brain-to-plasma partition coefficient (VT-NLME) was calculated. Our model indicated that tariquidar enhances brain uptake of (R)-[11C]verapamil by decreasing Qout. The reduction in Qout in rats during and immediately after tariquidar administration (sevenfold) was more pronounced than in the second PET scan acquired 2 h after tariquidar administration (fivefold). The effect of tariquidar on Qout in humans was apparent during and immediately after tariquidar administration (twofold reduction in Qout) but was negligible in the second PET scan. SE was found to influence the pharmacological volume of distribution of the central brain compartment Vbr1. Tariquidar treatment lead to an increase in VT-NLME, and pilocarpine-induced SE lead to increased (R)-[11C]verapamil distribution to the peripheral brain compartment. Using NLME modeling, we were able to provide mechanistic insight into the effects of tariquidar and SE on (R)-[11C]verapamil transport across the BBB in control and 48 h post SE rats as well as in humans.


Generation of supercoils in nicked and gapped DNA drives DNA unknotting and postreplicative decatenation.
Due to the helical structure of DNA the process of DNA replication is topologically complex. Freshly replicated DNA molecules are catenated with each other and are frequently knotted. For proper functioning of DNA it is necessary to remove all of these entanglements. This is done by DNA topoisomerases that pass DNA segments through each other. However, it has been a riddle how DNA topoisomerases select the sites of their action. In highly crowded DNA in living cells random passages between contacting segments would only increase the extent of entanglement. Using molecular dynamics simulations we observed that in actively supercoiled DNA molecules the entanglements resulting from DNA knotting or catenation spontaneously approach sites of nicks and gaps in the DNA. Type I topoisomerases, that preferentially act at sites of nick and gaps, are thus naturally provided with DNA-DNA juxtapositions where a passage results in an error-free DNA unknotting or DNA decatenation.


Obesity increases airway hyperresponsiveness via the TNF-α pathway and treating obesity induces recovery.
Obesity is a known risk factor for allergic asthma. It has been recognized as a key player in the pathogenesis of several inflammatory disorders via activation of macrophages, which is also vital to the development of allergic asthma. We investigated the mechanism of obesity-related asthma and whether treating obesity through exercise or diet ameliorates the severity of asthma in the obesity-related asthma model. We generated diet-induced obesity (DIO) in C57BL/6 mice by high-fat-feeding and ovalbumin-induced asthma (lean-OVA or DIO-OVA). The DIO-OVA mice were then treated with tumor necrosis factor (TNF)-α neutralizing antibody as a TNF-α blockade or a Cl2MDP-containing liposome to induce an alveolar macrophage deficiency. To treat obesity, the DIO-OVA mice were under dietary restrictions or exercised. The pathophysiological and immunological responses were analyzed. Airway hyperresponsiveness (AHR), serum IgE and TNF-α levels in the lung tissue increased in the DIO-OVA mice compared to the lean-OVA mice. Both the TNF-α blockade and depletion of alveolar macrophages in the DIO-OVA mice decreased AHR compared to the DIO-OVA mice. Treating obesity by exercise or through dietary means also reduced pulmonary TNF-α levels and AHR in the DIO-OVA mice. These results suggest that restoring normal body weight is an appropriate strategy for reducing TNF-α levels, and controlling inflammation may help improve asthma severity and control in obesity-related asthma.


Access to primary and preventive care among foreign-born adults in Canada and the United States.
To conduct cross-country comparisons and assess the effect of foreign birth on access to primary and preventive care in Canada and the United States. Secondary data from the 2002 to 2003 Joint Canada-United States Survey of Health. Descriptive and comparative analyses were conducted, and logistic regression models were used to assess the effect of immigrant status and country of residence on access to care. Outcomes included measures of health care systems and processes, utilization, and patient perceptions. In adjusted analyses, immigrants in Canada fared worse than nonimmigrants regarding having timely Pap tests; in the United States, immigrants fared worse for having a regular doctor and an annual consultation with a health professional. Immigrants in Canada had better access to care than immigrants in the United States; most of these differences were explained by differences in socioeconomic status and insurance coverage across the two countries. However, U.S. immigrants were more likely to have timely Pap tests than Canadian immigrants, even after adjusting for potential confounders. In both countries, foreign-born populations had worse access to care than their native-born counterparts for some indicators but not others. However, few differences in access to care were found when direct cross-country comparisons were made between immigrants in Canada versus the United States, after accounting for sociodemographic differences.


Inner to outer-sphere coordination of plutonium(iv) with N,N-dialkyl amide: influence of nitric acid.
N,N-Dialkylamides are extensively studied as alternative organic ligands to achieve the extraction and separation of uranium(vi) and plutonium(iv). We report here the coordination structures of the plutonium(iv) ion with N,N-di(2-ethylhexyl)-n-butanamide as a function of nitric acid concentration in the aqueous phase. The coordination structure of Pu(iv) evolves gradually with increasing nitric acid concentration from an inner-sphere with two coordinated amide ligands toward an outer-sphere hexanitrate complex with only nitrate ions in the first coordination sphere and protonated amide ligands in the outer shell.


Strategies to prevent and reduce diabetes and obesity in Sacramento, California: the African American Leadership Coalition and University of California, Davis.
Diabetes is one of the leading causes of illness and death for African Americans and people of African descent throughout the United States and in the city and county of Sacramento, California. The involvement of families and communities in developing prevention strategies can increase the likelihood that behavioral changes will be sustained. Three member organizations of the African American Leadership Coalition (AALC) entered into a partnership with the University of California, Davis (UC Davis) to engage families in developing a process to identify barriers to diabetes and obesity prevention and reduction, exchange strategies, and create action plans for prevention. The intervention comprised 3 phases: 1) coalition formation and training; 2) data collection, analysis, and dissemination of results; and 3) development of family and community action plans. Academic and community partners planned and implemented all project phases together. Sources of information about diabetes and obesity were primarily doctors and the Internet; barriers were related to lack of time needed to prepare healthy meals, high food costs, transportation to fresh markets, motivation around healthy habits, and unsafe environments. Action plans addressed behavioral change and family cohesion. The group discussion format encouraged mutual support and suggestions for better eating and physical exercise habits. This collaborative partnership model can strengthen existing group relationships or promote new affiliations that form the basis for future action coalitions. Participants worked both within and across groups to exchange information, stories of success and challenges, and specific health improvement strategies.


Research with Arctic peoples: unique research opportunities in heart, lung, blood and sleep disorders. Working group summary and recommendations.
Arctic peoples are spread over eight countries and comprise 3.74 million residents, of whom 9% are indigenous. The Arctic countries include Canada, Finland, Greenland (Denmark), Iceland, Norway, Russia, Sweden and the United States. Although Arctic peoples are very diverse, there are a variety of environmental and health issues that are unique to the Arctic regions, and research exploring these issues offers significant opportunities, as well as challenges. On July 28-29, 2004, the National Heart, Lung, and Blood Institute and the Canadian Institutes of Health Research co-sponsored a working group entitled "Research with Arctic Peoples: Unique Research Opportunities in Heart, Lung, Blood and Sleep Disorders". The meeting was international in scope with investigators from Greenland, Iceland and Russia, as well as Canada and the United States. Multiple health agencies from Canada and the United States sent representatives. Also attending were representatives from the International Union for Circumpolar Health (IUCH) and the National Indian Health Board. The working group developed a set of ten recommendations related to research opportunities in heart, lung, blood and sleep disorders; obstacles and solutions to research implementation; and ways to facilitate international comparisons. These recommendations are expected to serve as an agenda for future research.


Cloning and characterization of the Xenopus laevis p8 gene.
The p8 gene encodes a transcription factor with a basic helix-loop-helix motif and has been cloned in rat, mouse and human. It is upregulated in acute pancreatitis. In the present study, the Xenopus laevis homolog of p8 (Xp8) was isolated by PCR. The full-length Xp8 cDNA consists of 677 bp and encodes 82 amino acids. The basic helix-loop-helix region is well conserved between X. laevis and mammals. Overexpression of an Xp8-EGFP fusion protein indicated that Xp8 was localized to nucleus, as in mammals. Analysis by RT-PCR showed that expression of Xp8 was increased after gastrulation and maintained into later developmental stages. Expression was detected in the prospective neural region at the neurula stage by whole-mount in situ hybridization. At the larval stage, Xp8 was expressed in central nervous regions, such as ventrolateral brain, trigeminal nerve, vestibulocochlear nerve and dorsal neural tube. Expression was also detected in the basal cement gland, olfactory placode, ear vesicle, notochord and anus. This specific pattern of expression suggests that Xp8 may play a role in the development of the central nervous system in X. laevis.


Evaluating the selection, training, and support of peer support workers in the United Kingdom.
This article describes the preparation, selection, training, and support of a group of people with lived experience of mental distress/illness and mental health service use to work as peer support workers (PSWs). The PSWs were recruited to provide support alongside conventional aftercare to service users discharged from acute psychiatric units in London, England. Training was delivered over 12 weekly, 1-day sessions from April to July 2010. Supervision and support were provided by a peer support coordinator and a training facilitator. The overall view of the training by those who went on to work as PSWs was that it was a valuable, challenging, yet positive experience that provided them with a good preparation for the role. A key area for improvement concerned the strength of emotional involvement and feelings PSWs had for their peers, especially in regard to ending the support relationship. Skilled, sensitive supervision and support is essential for the success of such roles.


Effect of Embryo Banking on U.S. National Assisted Reproductive Technology Live Birth Rates.
Assisted Reproductive Technology (ART) reports generated by the Centers for Disease Control and Prevention (CDC) exclude embryo banking cycles from outcome calculations. We examined data reported to the CDC in 2013 for the impact of embryo banking exclusion on national ART outcomes by recalculating autologous oocyte ART live birth rates. Inflation of reported fresh ART cycle live birth rates was assessed for all age groups of infertile women as the difference between fresh cycle live births with reference to number of initiated fresh cycles (excluding embryo banking cycles), as typically reported by the CDC, and fresh cycle live births with reference to total initiated fresh ART cycles (including embryo banking cycles). During 2013, out of 121,351 fresh non-donor ART cycles 27,564 (22.7%) involved embryo banking. The proportion of banking cycles increased with female age from 15.5% in women <35 years to 56.5% in women >44 years. Concomitantly, the proportion of thawed cycles decreased with advancing female age (P <0.0001). Exclusion of embryo banking cycles led to inflation of live birth rates in fresh ART cycles, increasing in size in parallel to advancing female age and utilization of embryo banking, reaching 56.3% in women age >44. The inflation of live birth rates in thawed cycles could not be calculated from the publically available CDC data but appears to be even greater. Utilization of embryo banking increased during 2013 with advancing female age, suggesting a potential age selection bias. Exclusion of embryo banking cycles from national ART outcome reports significantly inflated national ART success rates, especially among older women. Exclusion of embryo banking cycles from US National Assisted Reproductive Technology outcome reports significantly inflates reported success rates especially in older women.


CT Male Pelvic Organ Segmentation via Hybrid Loss Network With Incomplete Annotation.
Sufficient data with complete annotation is essential for training deep models to perform automatic and accurate segmentation of CT male pelvic organs, especially when such data is with great challenges such as low contrast and large shape variation. However, manual annotation is expensive in terms of both finance and human effort, which usually results in insufficient completely annotated data in real applications. To this end, we propose a novel deep framework to segment male pelvic organs in CT images with incomplete annotation delineated in a very user-friendly manner. Specifically, we design a hybrid loss network derived from both voxel classification and boundary regression, to jointly improve the organ segmentation performance in an iterative way. Moreover, we introduce a label completion strategy to complete the labels of the rich unannotated voxels and then embed them into the training data to enhance the model capability. To reduce the computation complexity and improve segmentation performance, we locate the pelvic region based on salient bone structures to focus on the candidate segmentation organs. Experimental results on a large planning CT pelvic organ dataset show that our proposed method with incomplete annotation achieves comparable segmentation performance to the state-of-the-art methods with complete annotation. Moreover, our proposed method requires much less effort of manual contouring from medical professionals such that an institutional specific model can be more easily established.


Towards a Universal SMILES representation - A standard method to generate canonical SMILES based on the InChI.
There are two line notations of chemical structures that have established themselves in the field: the SMILES string and the InChI string. The InChI aims to provide a unique, or canonical, identifier for chemical structures, while SMILES strings are widely used for storage and interchange of chemical structures, but no standard exists to generate a canonical SMILES string. I describe how to use the InChI canonicalisation to derive a canonical SMILES string in a straightforward way, either incorporating the InChI normalisations (Inchified SMILES) or not (Universal SMILES). This is the first description of a method to generate canonical SMILES that takes stereochemistry into account. When tested on the 1.1 m compounds in the ChEMBL database, and a 1 m compound subset of the PubChem Substance database, no canonicalisation failures were found with Inchified SMILES. Using Universal SMILES, 99.79% of the ChEMBL database was canonicalised successfully and 99.77% of the PubChem subset. The InChI canonicalisation algorithm can successfully be used as the basis for a common standard for canonical SMILES. While challenges remain - such as the development of a standard aromatic model for SMILES - the ability to create the same SMILES using different toolkits will mean that for the first time it will be possible to easily compare the chemical models used by different toolkits.