[Slipped femoral epiphysis in children under 10 years of age. Clinical and radiologic evaluation of the surgical treatment].
Analyze the postoperative clinical and radiographic results of children under 10 years of age with slipped proximal femoral epiphysis and determine the differences compared to other age groups. Retrospective study with a minimum follow-up of 2 years; Southwick's angle, treatment, and the rate of contralateral slip were all assessed. The Iowa scale was used for assessment purposes. A total of 18 patients and 23 hips were reported (5 cases were bilateral), mean age was 8.53 years, and Southwick's angle was 43 degrees. All cases were treated with in situ fixation, with a single screw in 19 hips, Kirschner's nails in 2 hips, and one screw and one nail in one hip; prophylactic fixation was used in one hip. Mean follow-up was 6.9 years. Three cases had contralateral slip occurring 6-13 months after the initial slip. The mean Iowa score was 85.69. A neck-shaft angle of 115 degrees was seen in the final X-ray; there were 3 complications: two cases of avascular necrosis and one chondrolysis. The clinical results were similarly good in this group of patients, who have typically been considered as very difficult to treat. Radiographically, a relatively normal anatomy was seen and only one case showed early arthrosis. The contralateral slip rate was not higher than in older patients.


Unsupervised dealiasing and denoising of color-Doppler data.
Color Doppler imaging (CDI) is the premiere modality to analyze blood flow in clinical practice. In the prospect of producing new CDI-based tools, we developed a fast unsupervised denoiser and dealiaser (DeAN) algorithm for color Doppler raw data. The proposed technique uses robust and automated image post-processing techniques that make the DeAN clinically compliant. The DeAN includes three consecutive advanced and hands-off numerical tools: (1) statistical region merging segmentation, (2) recursive dealiasing process, and (3) regularized robust smoothing. The performance of the DeAN was evaluated using Monte-Carlo simulations on mock Doppler data corrupted by aliasing and inhomogeneous noise. Fifty aliased Doppler images of the left ventricle acquired with a clinical ultrasound scanner were also analyzed. The analytical study demonstrated that color Doppler data can be reconstructed with high accuracy despite the presence of strong corruption. The normalized RMS error on the numerical data was less than 8% even with signal-to-noise ratio as low as 10dB. The algorithm also allowed us to recover highly reliable Doppler flows in clinical data. The DeAN is fast, accurate and not observer-dependent. Preliminary results showed that it is also directly applicable to 3-D data. This will offer the possibility of developing new tools to better decipher the blood flow dynamics in cardiovascular diseases.


Evolution of the Na,K- and H,K-ATPase beta subunit gene family: structure of the murine Na,K-ATPase beta 2 subunit gene.
We have cloned and characterized the mouse Na,K-ATPase beta 2 subunit gene (Atp1b2). The gene spans approximately 7 kb and is split into seven exons. The transcription initiation site has been mapped and consensus TATA and putative CAAT sequences have been found at positions -23 and -137, respectively. Discrete structural domains of the beta 2 subunit protein are encoded by separate exons: The intracellular amino-terminal and putative transmembrane domains are encoded by individual exons and the extracellular carboxyl-terminal domain is encoded by five exons. The exon/intron organization of the beta 2 subunit gene closely resembles that of the H,K-ATPase beta subunit gene, suggesting that these two genes evolved from a common evolutionary ancestor. Comparison of the promoter region of the mouse and rat beta 2 subunit genes reveals a remarkably high degree of homology within a 788-nucleotide segment immediately upstream of the transcription start site. This observation suggests that elements that serve to regulate the cell-specific expression of the beta 2 subunit gene are likely to be located within this conserved region.


Occurrence, fate, and persistence of gemfibrozil in water and soil.
Pharmaceuticals and personal care products (PPCPs) have emerged as a group of potential environmental contaminants of concern. The occurrence of gemfibrozil, a lipid-regulating drug, was studied in the influent and effluent at a wastewater treatment plant (WWTP) and groundwater below a land application site receiving treated effluent from the WWTP. In addition, the sorption of gemfibrozil in two loam soils and sand was assessed, and biological degradation rates in two soil types under aerobic conditions were also determined. Results showed that concentrations of gemfibrozil in wastewater influent, effluent, and groundwater were in the range of 3.47 to 63.8 µg/L, 0.08 to 19.4 µg/L, and undetectable to 6.86 µg/L, respectively. Data also indicated that gemfibrozil in the wastewater could reach groundwater following land application of the treated effluent. Soil-water distribution coefficients for gemfibrozil, determined by the batch equilibrium method, varied with organic carbon content in the soils. The sorption capacity was silt loam > sandy loam > sand. Under aerobic conditions, dissipation half-lives for gemfibrozil in sandy loam and silt loam soils were 17.8 and 20.6 days, respectively; 25.4 and 11.3% of gemfibrozil was lost through biodegradation from the two soils over 14 days.


The effect of a three month, low-load- high-repetitions group-based exercise program versus pilates on physical fitness and body composition in inactive women.
Both low-load-high-repetitions (LLHR) and Pilates programs constitute popular forms of exercise, accompanied by health benefits for the participants involved. Notably, the effect of such programs on aerobic fitness is still controversial. The aim of this study was to examine the effects of both programs on physical fitness and body composition on previously inactive adult women. Twenty-six women (39.8 ± 9.1y) were assigned to a LLHR program, and sixteen women (39.1 ± 12.2y) were assigned to a Pilates program. Both programs were performed in a group setting, 3 times per week for 3 months. Aerobic fitness, flexibility, handgrip strength and lower extremities explosiveness were assessed by a battery of field testing. Total body fat and trunk fat levels were assessed by bioelectrical impedance analysis. Heart rate response during exercise was recorded once every month by using a telemetry system. Aerobic fitness, lower extremities explosive power, left arm handgrip strength and body composition significantly improved in the LLHR group; while flexibility significantly improved only in the Pilates group, following the intervention period (p < 0.05). LLHR was superior to the Pilates program in improving aerobic fitness and body composition; whilst Pilates was superior in improving flexibility (p < 0.05). LLHR group-based exercise programs may improve various aspects of physical fitness, including aerobic fitness, in inactive adult women. This medium-intensity form of exercise is generally well tolerated and might be used as an option for women who cannot perform training on higher intensities. In contrast, the Pilates program failed to improve physical fitness-related parameters except flexibility levels.


Exploring connectivity of the brain's white matter with dynamic queries.
Diffusion Tensor Imaging (DTI) is a magnetic resonance imaging method that can be used to measure local information about the structure of white matter within the human brain. Combining DTI data with the computational methods of MR tractography, neuroscientists can estimate the locations and sizes of nerve bundles (white matter pathways) that course through the human brain. Neuroscientists have used visualization techniques to better understand tractography data, but they often struggle with the abundance and complexity of the pathways. In this paper, we describe a novel set of interaction techniques that make it easier to explore and interpret such pathways. Specifically, our application allows neuroscientists to place and interactively manipulate box or ellipsoid-shaped regions to selectively display pathways that pass through specific anatomical areas. These regions can be used in coordination with a simple and flexible query language which allows for arbitrary combinations of these queries using Boolean logic operators. A representation of the cortical surface is provided for specifying queries of pathways that may be relevant to gray matter structures and for displaying activation information obtained from functional magnetic resonance imaging. By precomputing the pathways and their statistical properties, we obtain the speed necessary for interactive question-and-answer sessions with brain researchers. We survey some questions that researchers have been asking about tractography data and show how our system can be used to answer these questions efficiently.


Building a Competing Endogenous RNA Network to Find Potential Long Non-Coding RNA Biomarkers for Pheochromocytoma.
Accumulating evidence has shown that long non-coding RNAs (lncRNAs) in competing endogenous RNA (ceRNA) networks play crucial roles in tumor survival and patient prognosis; however, studies investigating ceRNA networks in pheochromocytoma (PCC) are lacking. In this study, we investigated the pathogenesis of PCC and whether lncRNAs acting through ceRNAs networks were associated with prognosis. A total of 183 PCC samples and 3 control samples from The Cancer Genome Atlas database were analyzed. The Empirical Analysis of Digital Gene Expression Data package in R (edgeR) was used to analyze differentially expressed RNAs. Biological processes and pathways functional enrichment analysis were performed based on the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database. LncRNA/mRNA/miRNA ceRNA network was constructed by Cytoscape v3.0 software based on the differentially expressed RNAs Survival package in R was used to perform survival analysis. In total, 554 differentially expressed lncRNAs, 1775 mRNAs and 40 miRNAs were selected for further analysis. Subsequently, 23 lncRNAs, 22 mRNAs, and 6 miRNAs were included in the constructed ceRNA network. Meanwhile, two of the 23 lncRNAs (C9orf147 and BSN-AS2) were identified as independent predictors of overall survival in PCC patients (P< 0.05). This study improves the understanding of lncRNA-related ceRNA networks in PCC and suggests that the lncRNAs C9orf147 and BSN-AS2 could be independent prognostic biomarkers and potential therapeutic targets for PCC.


SNPPicker: high quality tag SNP selection across multiple populations.
Linkage Disequilibrium (LD) bin-tagging algorithms identify a reduced set of tag SNPs that can capture the genetic variation in a population without genotyping every single SNP. However, existing tag SNP selection algorithms for designing custom genotyping panels do not take into account all platform dependent factors affecting the likelihood of a tag SNP to be successfully genotyped and many of the constraints that can be imposed by the user. SNPPicker optimizes the selection of tag SNPs from common bin-tagging programs to design custom genotyping panels. The application uses a multi-step search strategy in combination with a statistical model to maximize the genotyping success of the selected tag SNPs. User preference toward functional SNPs can also be taken into account as secondary criteria. SNPPicker can also optimize tag SNP selection for a panel tagging multiple populations. SNPPicker can optimize custom genotyping panels including all the assay-specific constraints of Illumina's GoldenGate and Infinium assays. A new application has been developed to maximize the success of custom multi-population genotyping panels. SNPPicker also takes into account user constraints including options for controlling runtime. Perl Scripts, Java source code and executables are available under an open source license for download at http://mayoresearch.mayo.edu/mayo/research/biostat/software.cfm.


Socio-economic status in relation to risk factors associated with cardiovascular disease, in healthy individuals from the ATTICA study.
Social status has been related with the prevalence and incidence of cardiovascular disease. The aim of this study is to investigate the relationships between socio-economic status (SES) and clinical and biochemical factors related to coronary heart disease, in a sample of cardiovascular disease-free men and women. Cross-sectional survey. During 2001-2002, 1514 men (20-87 years old) and 1528 women (20-89 years old) from the Attica region (Greece) were randomly enrolled into the study. Trends in established and emerging cardiovascular risk factors were examined across the participants' socio-economic status. A special index was developed (years of school by annual income) and three socio-economic classes were created. An inverse relationship was found regarding all lipids and glucose levels across the tertiles of the SES index. An inverse association was observed between body mass index, waist-to-hip ratio and SES in men, but not in women. Furthermore, compared to the lowest tertile, individuals who were classified in the highest SES tertile had lower levels of C-reactive protein, fibrinogen, homocysteine, tumour necrosis factor-alpha, interleukin-6 levels and white blood cell counts, even after adjusting for various potential confounders. Finally, a considerable proportion of men and women reported lack of health knowledge and education. An inverse association between SES and factors related to cardiovascular risk exists, but the causal pathway itself requires more detailed explanation before the social status can have explanatory power.


The additional yield of a periodic screening programme for open-angle glaucoma: a population-based comparison of incident glaucoma cases detected in regular ophthalmic care with cases detected during screening.
To study the additional yield of a periodic screening programme for open-angle glaucoma (OAG) by comparing, in a population-based setting, incident OAG (iOAG) cases detected in regular ophthalmic care with those detected during screening. Participants aged 55 and over from the population-based Rotterdam Study underwent the same ophthalmic examination at baseline (1991-3) and follow-up (1997-9), including visual field testing and simultaneous stereo optic disc photography. Of 3842 participants, 87 (2.3%) developed iOAG during a mean follow-up time of 6.5 years. Of these 87 iOAG cases, 78 (90%) were included in this study. Of the 78 iOAG cases detected at follow-up, 23 (29%) had already been detected before during regular ophthalmic care. The remaining 55 (71%) undetected iOAG cases more often showed glaucomatous optic neuropathy without glaucomatous visual field loss (29 of 55 (53%)) as compared with the detected cases (four of 23 (17%); p = 0.009). Of the undetected iOAG cases, only four had developed significant visual field loss in their better eye. The additional yield of a periodic OAG screening programme is lower than expected from published prevalence data. In the discussion, the authors estimate that-in a white population with a low prevalence of pseudoexfoliation-about one in 1000 screened persons could be saved from bilateral end-stage OAG.


Partial breast irradiation. Patient selection, guidelines for treatment, and current results.
Studies evaluating selected patients treated with partial breast irradiation (PBI) in accelerated fractionation schemes have demonstrated the equivalence of PBI with traditional whole-breast irradiation. The major advantage of PBI is the time compression of treatment down to less than 1 week compared with 6.5 weeks for whole-breast external beam treatments. Four techniques are available to deliver PBI. These include interstitial brachytherapy multicatheter systems, the Mammosite Radiation Therapy System applicator, external beam three-dimensional conformal radiation therapy and intraoperative radiation therapy. For the two brachytherapy techniques of multicatheter implantation and the Mammosite, accurate placement is achieved with image guidance via intraoperative ultrasonography, mammography, and/or CT scanning. Technologies such as image-guided cone beam CT assure accurate delivery of PBI with external beam three-dimensional conformal radiation therapy. Results of PBI show excellent control rates with mild toxicities; cosmetic outcomes are good to excellent in the vast majority of patients.


The effect of alterations in activity and body temperature on the pulmonary surfactant system in the lesser long-eared bat Nyctophilus geoffroyi.
Pulmonary surfactant is a mixture of phospholipids, neutral lipids and proteins that controls the surface tension of the fluid lining the lung. It is critical for lung stability and function. The amount and composition of surfactant are influenced by physiological variables such as metabolic rate, body temperature and ventilation. We investigated the plasticity of the pulmonary surfactant system in the microchiropteran bat Nyctophilus geoffroyi throughout a natural 24 h cycle. Bats were housed at 24 degrees C on a fixed (8 h:16 h) light:dark photoperiod. At 4 h intervals throughout the 24 h period, bats were lavaged and the surfactant analysed for absolute and relative amounts of total phospholipid (PL), disaturated phospholipid (DSP) and cholesterol (Chol). N. geoffroyi experienced two peaks of activity, at 18:00 h and 06:00 h. The amount of surfactant increased 1.5-fold upon arousal from torpor. The proportion of DSP to PL in the surfactant remained constant. Similarly, the Chol/PL and Chol/DSP ratios remained relatively constant. Surfactant cholesterol content did not increase during torpor in N. geoffroyi. Cholesterol does not appear to control surfactant fluidity during torpor in these bats, but instead the cholesterol content exactly mirrored the diurnal changes in body temperature.


Three physiotherapy protocols: effects on pulmonary volumes after cardiac surgery.
To evaluate inspiratory volume in patients undergoing cardiac surgery and to determine the effects that incentive spirometry (IS) and the breath stacking (BS) technique have on the recovery of FVC in such patients. A prospective, controlled, randomized clinical trial involving 35 patients undergoing cardiac surgery at the Hospital de Força Aérea do Galeão (HFAG, Galeão Air Force Hospital), in the city of Rio de Janeiro, Brazil. The patients, all of whom performed mobilization and cough procedures, were randomly divided into three groups: exercise control (EC), performing only the abovementioned procedures; IS, performing the abovementioned procedures and instructed to take long breaths using an incentive spirometer; and BS, performing the abovementioned procedures, together with successive inspiratory efforts using a facial mask coupled to a unidirectional valve. Forced spirometry was carried out in the preoperative period and on postoperative days 1 to 5. During the maneuvers, inspiratory volume was measured in the IS and BS groups. On postoperative day 1, FVC significantly decreased in all groups (EC: 87.1 vs. 32.0%; IS: 75.3 vs. 29.5%; and BS: 81.9 vs. 33.2%; p < 0.001 for all), as did inspiratory volume in the IS and BS groups (2.29 vs. 0.82 L; and 2.56 vs. 1.34 L, respectively; p < 0.001 for both). Between postoperative days 1 and 5, FVC partially normalized in all groups (EC: 32.0 vs. 51.3%; IS: 29.5 vs. 46.7%; and BS: 33.3 vs. 54.3%; p < 0.001 for all). During the postoperative period, inspiratory volume was significantly higher in the BS group than in the IS group. The three protocols were equivalent concerning the recovery of FVC on the first five postoperative days. When compared with IS, the BS technique promoted higher inspiratory volumes in this sample of postoperative cardiac patients.


Recent advances in knowledge of the structure and function of the angiotensin I converting enzyme.
To review the structure and function of the angiotensin I converting enzyme (ACE), focusing on recent results from studies using a wide range of molecular biological techniques. ACE is an ectoenzyme expressed as two isoenzymes in mammals, a larger somatic form found in endothelial, epithelial and neuronal tissues and a smaller form in germinal tissues. Both forms have similar enzymatic activities but differ in size and immunological properties. The somatic form of ACE is composed of two highly homologous domains (amino and carboxyl domains) while the germinal form contains only one domain. Somatic ACE has two functional catalytic sites, both dependent on a zinc cofactor. Each ACE domain has also been shown to interact differently with competitive inhibitors. The mechanism for anchoring ACE to the cell membrane has also been reported, and the solubilization step outlined. The relationship between the membrane-bound and soluble forms has been investigated, and the physiological relevance of this mechanism discussed. The structure of the ACE gene has been determined and the distribution in cells and different tissues has been reported in various studies. All results have indicated that there are important functional and structural differences between the two domains, but at present ACE cannot be considered a true bifunctional enzyme, even though an exclusive substrate has been identified for the amino domain.


Non-additive gene regulation in a citrus allotetraploid somatic hybrid between C. reticulata Blanco and C. limon (L.) Burm.
Polyploid plants often produce new phenotypes, exceeding the range of variability existing in the diploid gene pool. Several hundred citrus allotetraploid hybrids have been created by somatic hybridization. These genotypes are interesting models to study the immediate effects of allopolyploidization on the regulation of gene expression. Here, we report genome-wide gene expression analysis in fruit pulp of a Citrus interspecific somatic allotetraploid between C. reticulata cv 'Willowleaf mandarin'+C. limon cv 'Eureka lemon', using a Citrus 20K cDNA microarray. Around 4% transcriptome divergence was observed between the two parental species, and 212 and 160 genes were more highly expressed in C. reticulata and C. limon, respectively. Differential expression of certain genes was confirmed by quantitative real-time RT-PCR. A global downregulation of the allotetraploid hybrid transcriptome was observed, as compared with a theoretical mid parent, for the genes displaying interspecific expression divergence between C. reticulata and C. limon. The genes underexpressed in mandarin, as compared with lemon, were also systematically repressed in the allotetraploid. When genes were overexpressed in C. reticulata compared with C. limon, the distribution of allotetraploid gene expression was far more balanced. Cluster analysis on the basis of gene expression clearly indicated the hybrid was much closer to C. reticulata than to C. limon. These results suggest there is a global dominance of the mandarin transcriptome, in consistence with our previous studies on aromatic compounds and proteomics. Interspecific differentiation of gene expression and non-additive gene regulation involved various biological pathways and different cellular components.


Pembrolizumab for Early Triple-Negative Breast Cancer.
Previous trials showed promising antitumor activity and an acceptable safety profile associated with pembrolizumab in patients with early triple-negative breast cancer. Whether the addition of pembrolizumab to neoadjuvant chemotherapy would significantly increase the percentage of patients with early triple-negative breast cancer who have a pathological complete response (defined as no invasive cancer in the breast and negative nodes) at definitive surgery is unclear. In this phase 3 trial, we randomly assigned (in a 2:1 ratio) patients with previously untreated stage II or stage III triple-negative breast cancer to receive neoadjuvant therapy with four cycles of pembrolizumab (at a dose of 200 mg) every 3 weeks plus paclitaxel and carboplatin (784 patients; the pembrolizumab-chemotherapy group) or placebo every 3 weeks plus paclitaxel and carboplatin (390 patients; the placebo-chemotherapy group); the two groups then received an additional four cycles of pembrolizumab or placebo, and both groups received doxorubicin-cyclophosphamide or epirubicin-cyclophosphamide. After definitive surgery, the patients received adjuvant pembrolizumab or placebo every 3 weeks for up to nine cycles. The primary end points were a pathological complete response at the time of definitive surgery and event-free survival in the intention-to-treat population. At the first interim analysis, among the first 602 patients who underwent randomization, the percentage of patients with a pathological complete response was 64.8% (95% confidence interval [CI], 59.9 to 69.5) in the pembrolizumab-chemotherapy group and 51.2% (95% CI, 44.1 to 58.3) in the placebo-chemotherapy group (estimated treatment difference, 13.6 percentage points; 95% CI, 5.4 to 21.8; P<0.001). After a median follow-up of 15.5 months (range, 2.7 to 25.0), 58 of 784 patients (7.4%) in the pembrolizumab-chemotherapy group and 46 of 390 patients (11.8%) in the placebo-chemotherapy group had disease progression that precluded definitive surgery, had local or distant recurrence or a second primary tumor, or died from any cause (hazard ratio, 0.63; 95% CI, 0.43 to 0.93). Across all treatment phases, the incidence of treatment-related adverse events of grade 3 or higher was 78.0% in the pembrolizumab-chemotherapy group and 73.0% in the placebo-chemotherapy group, including death in 0.4% (3 patients) and 0.3% (1 patient), respectively. Among patients with early triple-negative breast cancer, the percentage with a pathological complete response was significantly higher among those who received pembrolizumab plus neoadjuvant chemotherapy than among those who received placebo plus neoadjuvant chemotherapy. (Funded by Merck Sharp & Dohme [a subsidiary of Merck]; KEYNOTE-522 ClinicalTrials.gov number, NCT03036488.).


The Therapeutic Potential of Differentiated Lung Cells from Embryonic Stem Cells in Lung Diseases.
Lung diseases cause great morbidity and mortality. The choice of effective medical treatment is limited and the number of lung diseases are difficult to treat with current treatments. The embryonic stem cells (ESCs) have the potential to differentiate into cell types of all three germinal layers, including lung epithelial cells. So they can be a potential source for new cell therapies for hereditary or acquired diseases of the airways and lungs. One method for treatment of lung diseases is cell therapy and the use of ESCs that can replace the damaged epithelial and endothelial cells. Progress using ESCs has developed slowly for lung regeneration because differentiation of lung cells from ESCs is more difficult as compared to differentiation of other cells. The review studies the therapeutic effects of differentiated lung cells from embryonic stem cells in lung diseases. There are few studies of differentiation of ESCs into a lineage of respiratory and then investigation of this cell in experimental model of lung diseases.


Spatiotemporal Temperature Distribution of NIR Irradiated Polypyrrole Nanoparticles and Effects of pH.
The spatiotemporal temperature distributions of NIR irradiated polypyrrole nanoparticles (PPN) were evaluated by varying PPN concentrations and the pH of suspensions. The PPN were synthesized by oxidative chemical polymerization, resulting in a hydrodynamic diameter of 98 ± 2 nm, which is maintained in the pH range of 4.2-10; while the zeta potential is significantly affected, decreasing from 20 ± 2 mV to -5 ± 1 mV at the same pH range. The temperature profiles of PPN suspensions were obtained using a NIR laser beam (1.5 W centered at 808 nm). These results were analyzed with a three-dimensional predictive unsteady-state heat transfer model that considers heat conduction, photothermal heating from laser irradiation, and heat generation due to the water absorption. The temperature profiles of PPN under laser irradiation are concentration-dependent, while the pH increase only induces a slight reduction in the temperature profiles. The model predicts a value of photothermal transduction efficiency (η) of 0.68 for the PPN. Furthermore, a linear dependency was found for the overall heat transfer coefficient (U) and η with the suspension temperature and pH, respectively. Finally, the model developed in this work could help identify the exposure time and concentration doses for different tissues and cells (pH-dependent) in photothermal applications.


Market forces influence helping behaviour in cooperatively breeding paper wasps.
Biological market theory is potentially useful for understanding helping behaviour in animal societies. It predicts that competition for trading partners will affect the value of commodities exchanged. It has gained empirical support in cooperative breeders, where subordinates help dominant breeders in exchange for group membership, but so far without considering one crucial aspect: outside options. We find support for a biological market in paper wasps, Polistes dominula. We first show that females have a choice of cooperative partners. Second, by manipulating entire subpopulations in the field, we increase the supply of outside options for subordinates, freeing up suitable nesting spots and providing additional nesting partners. We predicted that by intensifying competition for help, our manipulation would force dominants to accept a lower price for group membership. As expected, subordinates reduce their foraging effort following our treatments. We conclude that to accurately predict the amount of help provided, social units cannot be viewed in isolation: the surrounding market must also be considered.


DFT modelling of explicit solid-solid interfaces in batteries: methods and challenges.
Density Functional Theory (DFT) calculations of electrode material properties in high energy density storage devices like lithium batteries have been standard practice for decades. In contrast, DFT modelling of explicit interfaces in batteries arguably lacks universally adopted methodology and needs further conceptual development. In this paper, we focus on solid-solid interfaces, which are ubiquitous not just in all-solid state batteries; liquid-electrolyte-based batteries often rely on thin, solid passivating films on electrode surfaces to function. We use metal anode calculations to illustrate that explicit interface models are critical for elucidating contact potentials, electric fields at interfaces, and kinetic stability with respect to parasitic reactions. The examples emphasize three key challenges: (1) the "dirty" nature of most battery electrode surfaces; (2) voltage calibration and control; and (3) the fact that interfacial structures are governed by kinetics, not thermodynamics. To meet these challenges, developing new computational techniques and importing insights from other electrochemical disciplines will be beneficial.


Recent advancements in polyethyleneimine-based materials and their biomedical, biotechnology, and biomaterial applications.
Cationic polymers, known for their highly positive charges, have historically dominated the materials used in bioengineering. However, the demand for intelligent systems with high efficiency, bio-mimetic and tunable features is increasing. Artificial composites that mimic biorecognition and periodic structures may propel the development of advanced materials with outstanding properties. Polyethyleneimines (PEIs) constitute a valuable class of polycations because they have repetitive structural units, a wide molecular weight range and flexible polymeric chains, which facilitate customization of functional composites. Specific advantageous features could be introduced by purposeful modification or functionalization, such as specificity and sensitivity, distinct geometry, biocompatibility, and long service life. Thus, PEIs have been rapidly used in a wide range of applications in the fields of biomedicine, biotechnology and biomaterials science. This article provides an overview of recent advancements in the fabrication of PEI-based materials and corresponding applications in gene and drug delivery, bio-inhibitors, bio-separation, bioimaging, cell culture, and production of antibacterial and self-healing materials. The effects of molecular weight, topological structure, positive charges and hydrophilic properties on the performance of PEIs have been illustrated in detail. Finally, current technological limitations, research challenges, and future aspects are also discussed.


Immunohistochemistry Use by Diagnostic Category and Pathologist in 4477 Prostate Core Biopsy Sets Assessed at Two Hospitals.
Immunohistochemistry (IHC) use in prostate cores is not routinely determined and its value assessed. Pathology reports for cases accessioned 2011 to 2017 at two hospitals were retrieved. IHC orders by pathologist and hospital were extracted with a custom program and tabulated. The diagnostic category (and highest grade cancer if applicable) was obtained by a hierarchical (free text) string matching algorithm. The study period contained 4477 biopsy sets. Categorized by worst pathology (% stained), the cohort was: benign: 1184 cases (42%); prostatic intraepithelial neoplasia: 168 (68%); suspicious: 323 (93%); grade group 1 cancer (WHO1): 900 (78%); grade group two (WHO2): 840 (60%); WHO3 cancer: 451 (54%); WHO4 cancer: 363 (46%); WHO5 cancer: 215 (56%); cancer grade not specified: 33 (52%). The hospital was a predictor; site A(2716 biopsies) and site B(1761) accounted for 10,183 and 14,852 IHC, respectively. The cases with IHC decreased in the last 4 years (site A: 57->45%, site B: 79->73%). Thirty-five pathologists read >20 cases each and together interpreted 4418 (range, 21 to 415; median, 88). In total 24,766 IHCs were done on the 4,418 cases (5.6/case). The mean/median/SD/max/min IHCs/case for the 35 pathologists was 5.6/4.1/3.9/15.2/0.9. High IHC users (1st and 2nd quintile pathologists) called more suspicious for malignancy but not significantly more WHO1 than low IHC users. IHC use is most frequent at the benign/malignant interface, and dependent on the pathologist and hospital; however, it is independent of WHO1 cancer rate. Diagnostic rate information can inform and define appropriate and rational IHC use. We plan to follow IHC utilization retrospectively in relation to the diagnostic category going forward.


[Cadmium tolerance and enrichment characteristics of Eulaliopsis binata].
A pot experiment was conducted to study the cadmium (Cd) tolerance and enrichment characteristics of Eulaliopsis binata. Applying low concentration Cd (5 mg x kg(-1)) could boost the growth and physiological vigor of E. binata, with the twelve indexes such as biomass and net photosynthetic rate, etc. increased by 1.0% -15.5%, compared with CK; while applying high concentration Cd (> 5 mg x kg(-1)) had negative effects on the growth of E. binata. Even though the E. binata still finished its physiological circle under the application of 100 mg Cd x kg(-1), the biomass and net photosynthetic rate were decreased by 27.0% and 25.6%, respectively, in comparison with CK. The Cd content in the organs of E. binata increased greatly with increasing concentration of applied Cd. The Cd content in roots was from 350 mg x kg(-1) to 500 mg x kg(-1), and that in stems and leaves was from 15 mg x kg(-1) to 35 mg x kg(-1). When the concentration of applied Cd was < 50 mg x kg(-1), the Cd uptake by E. binata increased with increasing concentration of applied Cd. The Cd content in stems and leaves amounted 15.7% - 38.4% of the total uptake, and the ratio of the Cd content in stems and leaves to that in roots was up to 0.62. All the results indicated that E. binata had stronger capability in tolerating, enriching, and transporting Cd, being a potential Cd hyperaccumulator.


PTEN: from pathology to biology.
The PTEN tumour suppressor gene is mutated frequently in many malignancies and its importance in the development of cancer is probably underestimated. As the primary phosphatase of phosphatidylinositol (3,4,5)-trisphosphate, PTEN has a central role in reigning in the phosphoinositide 3-kinase (PI 3-kinase) network to control cellular homeostasis. Cells that lack PTEN are unable to regulate the PtdIns 3-kinase programme, which stimulates a variety of cellular phenotypes that favour oncogenesis. As well as the well-known role as tumour suppressor, recent studies show that PTEN is involved in the regulation of several basic cellular functions, such as cell migration, cell size, contractility of cardiac myocytes and chemotaxis. Here, we review the roles of PTEN in normal cellular functions and disease development.


Subclinical atherosclerosis and history of cardiovascular events in Italian patients with rheumatoid arthritis: Results from a cross-sectional, multicenter GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale) study.
Several studies have pointed out a significant association between rheumatoid arthritis (RA) and accelerated atherosclerosis. At the best of our knowledge, no such study has been carried out in a large Italian series and, in this study, we aimed to investigate the prevalence of both subclinical atherosclerosis and history of cardiovascular events (CVEs), in patients consecutively admitted from January 1, 2015 to December 31, 2015 to Rheumatology Units throughout the whole Italy.Centers members of GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale) were invited to enrol patients consecutively admitted from January 1, 2015 to December 31, 2015 and satisfying American College of Rheumatology/ European League Against Rheumatism criteria for RA and to investigate each of them for: traditional cardiovascular risk factors: sex, age, smoking habit, total cholesterol, triglycerides, glycaemia, high blood pressure, metabolic syndrome (MS), type 2 diabetes (T2D); RA features: disease duration as assessed from the first symptom, disease activity as evaluated by DAS28, radiographic damage as assessed by hands and feet x-ray, and previous joint surgery; prevalence of both subclinical atherosclerosis and history of CVEs.Eight centers participated to the study. From January 1, 2015 to December 31, 2015, the 1176 patients, who had been investigated for all the items, were enrolled in the study. They were mostly women (80.52%), with a median age of 60 years (range, 18-91 years), a median disease duration of 12 years (range, 0.8-25 years), seropositive in 69.21%. Nineteen percent were in remission; 17.51% presented low disease activity; 39.45% moderate disease activity; 22.61% high disease activity.Eighty-two patients (6.9%) had a history for CVEs (58 myocardial infarction, 38 heart failure, 10 ischemic transitory attack, and 7 stroke). This figure appears to be lower than that reported worldwide (8.5%). After excluding the 82 patients with a history of CV events, subclinical atherosclerosis was detected in 16% of our patients, (176 patients), a figure lower than that reported worldwide (32.7%) and in previous Italian studies.This is the first Italian multicenter study on subclinical and clinical atherosclerosis in patients with RA. We pointed out a low prevalence of both subclinical atherosclerosis and history of CV events.


Ruxolitinib Re-Treatment in Patients with Myelofibrosis: Real-World Evidence on Patient Characteristics and Outcomes.
Ruxolitinib is an FDA-approved treatment of intermediate- and high-risk myelofibrosis. In the phase 3 COMFORT studies, ruxolitinib reduced spleen volume in patients with myelofibrosis, with a median time to response of 3 months. However, nearly 20% of patients discontinued by month 4 with few treatment options available following discontinuation of ruxolitinib treatment. In this study, 2 independent patient care data sources were queried (Cardinal Health Oncology Provider Extended Network [OPEN] and HealthCore Integrated Research Environment [HIRE®]), and a retrospective review of medical charts was conducted. Patients aged ≥18 years with a diagnosis of myelofibrosis (primary or secondary), use of ruxolitinib for myelofibrosis, and documented physician-directed ruxolitinib interruption were included. Among 26 included patients, pre-interruption median (interquartile range [IQR]) ruxolitinib treatment duration was 123 (57-391, OPEN) and 110 (37-148, HIRE) days. Half the patients interrupted treatment within 3 months, commonly for adverse events (42% and 71%, respectively). After restarting ruxolitinib, median (IQR) re-treatment duration was 196 (54-553) and 166 (108-262) days, respectively. Consistent with previous reports, symptoms and spleen size improved in (OPEN/HIRE) 45%/43% and 40%/33% of evaluable patients, respectively. Further studies investigating the management of dose modifications and interruptions are needed to optimize benefit from ruxolitinib therapy.


A controlled, before-and-after trial of an urban sanitation intervention to reduce enteric infections in children: research protocol for the Maputo Sanitation (MapSan) study, Mozambique.
Access to safe sanitation in low-income, informal settlements of Sub-Saharan Africa has not significantly improved since 1990. The combination of a high faecal-related disease burden and inadequate infrastructure suggests that investment in expanding sanitation access in densely populated urban slums can yield important public health gains. No rigorous, controlled intervention studies have evaluated the health effects of decentralised (non-sewerage) sanitation in an informal urban setting, despite the role that such technologies will likely play in scaling up access. We have designed a controlled, before-and-after (CBA) trial to estimate the health impacts of an urban sanitation intervention in informal neighbourhoods of Maputo, Mozambique, including an assessment of whether exposures and health outcomes vary by localised population density. The intervention consists of private pour-flush latrines (to septic tank) shared by multiple households in compounds or household clusters. We will measure objective health outcomes in approximately 760 children (380 children with household access to interventions, 380 matched controls using existing shared private latrines in poor sanitary conditions), at 2 time points: immediately before the intervention and at follow-up after 12 months. The primary outcome is combined prevalence of selected enteric infections among children under 5 years of age. Secondary outcome measures include soil-transmitted helminth (STH) reinfection in children following baseline deworming and prevalence of reported diarrhoeal disease. We will use exposure assessment, faecal source tracking, and microbial transmission modelling to examine whether and how routes of exposure for diarrhoeagenic pathogens and STHs change following introduction of effective sanitation. Study protocols have been reviewed and approved by human subjects review boards at the London School of Hygiene and Tropical Medicine, the Georgia Institute of Technology, the University of North Carolina at Chapel Hill, and the Ministry of Health, Republic of Mozambique. NCT02362932.


In vitro metabolic and respiratory acidosis selectively inhibit osteoblastic matrix gene expression.
Clinically, a decrease in blood pH may be due to either a reduction in bicarbonate concentration ([HCO(-)(3)], metabolic acidosis) or an increase in PCO(2) (respiratory acidosis). In mammals, metabolic acidosis induces a far greater increase in urine calcium excretion than respiratory acidosis. In cultured bone, metabolic acidosis induces a marked increase in calcium efflux and a decrease in osteoblastic collagen synthesis, whereas isohydric respiratory acidosis has little effect on either parameter. We have shown that metabolic acidosis prevents the normal developmental increase in the expression of RNA for matrix Gla protein and osteopontin in chronic cultures of primary murine calvarial bone cells (predominantly osteoblasts) but does not alter expression of osteonectin. To compare the effects of isohydric metabolic and respiratory acidosis on expression of these genes, bone cell cultures were incubated in medium at pH approximately 7.2 to model metabolic ([HCO(-)(3)], approximately 13 mM) or respiratory (PCO(2), approximately 80 mmHg) acidosis or at pH approximately 7.4 as a control. Cells were sampled at weeks 4, 5, and 6 to assess specific RNA content. At all time periods studied, both metabolic and respiratory acidosis inhibited the expression of RNA for matrix Gla protein and osteopontin to a similar extent, whereas there was no change in osteonectin expression. In contrast to the significant difference in the effects of metabolic and respiratory acidosis on bone calcium efflux and osteoblastic collagen synthesis, these two forms of acidosis have a similar effect on osteoblastic RNA expression of both matrix Gla protein and osteopontin. Thus, although several aspects of bone cell function are dependent on the type of acidosis, expression of these two matrix genes appears to be regulated by extracellular pH, independently of the type of acidosis.


Toward a quantitative understanding of viral phylogeography.
Phylogeographic approaches help uncover the imprint that spatial epidemiological processes leave in the genomes of fast evolving viruses. Recent Bayesian inference methods that consider phylogenetic diffusion of discretely and continuously distributed traits offer a unique opportunity to explore genotypic and phenotypic evolution in greater detail. To provide a taste of the recent advances in viral diffusion approaches, we highlight key findings arising at the intrahost, local and global epidemiological scales. We also outline future areas of research and discuss how these may contribute to a quantitative understanding of the phylodynamics of RNA viruses.


Noncollinear correlated photon pair source in the 1550 nm telecommunication band.
We present a source of noncollinear correlated photon pairs in the standard 1550 nm telecommunication band. They are generated by a spontaneous parametric down-conversion process and emitted in a cone because of type-I noncollinear phase matching. Within the band, the source gives a completely flexible choice of the frequencies of the photon pairs, and correlation properties related to spatial momentum as well as energy and time can easily be utilized.We characterize the source by measuring the spatial intensity distribution of the down-converted light and by performing coincidence counting.


Patients with early arthritis consume less alcohol than controls, regardless of the type of arthritis.
There are conflicting reports concerning the association between alcohol consumption and RA. We performed a case-control study to investigate the association of alcohol consumption with RA as well as with other forms of arthritis. To assess whether alcohol consumption affects long-term disease outcome, we also investigated its association with radiographic progression and sustained drug-free remission in RA. Patients with arthritis and various diagnoses including RA, OA, ReA, SpA and PsA were compared with 5868 controls from the general population. The association of disease with alcohol consumption was analysed by logistic regression analysis. Alcohol consumption was inversely associated with not only RA [odds ratio (OR) 0.28, 95% CI 0.23, 0.35] but also OA (OR 0.31, 95% CI 0.16, 0.62) and other forms of arthritis (OR 0.34, 95% CI 0.24, 0.48). A higher degree of systemic inflammation, reflected by the ESR and CRP level, was associated with a smaller proportion of patients consuming alcohol. There was no dose-response relationship between the amount of alcohol consumed and the presence of arthritis. The extent of joint destruction and the rate of sustained drug-free remission were not affected by alcohol consumption. Arthritis patients report less alcohol consumption than controls, regardless of the type of arthritis. This suggests that alcohol may either protect against different kinds of arthritis or that the inverse association between alcohol and arthritis may be secondary to disease development, with arthritis patients being less inclined to consume alcohol due to their decreased general well-being.


Neoplasms of the nasal passages and paranasal sinuses in domesticated animals as reported by 13 veterinary colleges.
Three hundred cases of primary neoplasms involving the nasal cavity or paranasal sinuses were found among the reports of 12,300 microscopically confirmed neoplasms. The multispecies data were compiled from abstracts of medical records by 13 colleges of veterinary medicine in the United States and Canada from 1964 to 1973. Significant numbers of neoplasms were observed in dogs, horses, and cats. Intranasal neoplasms were more frequent than those of the paranasal sinuses in dogs and cats. Only cats had a sex difference in the occurrence of nasal neoplasms, with a male predilection. The frequency of neoplasms of the nasal cavity and paranasal sinuses increased with age in all species examined. A clear relationship could not be established between nose length and of intranasal neoplasms. Of the tumors, 80% were malignant in dogs, 68% in horses, and 91% in cats. Detailed review of medical records in a subset of 49 dogs with neoplasms of the nasal passage and paranasal sinuses revealed major clinical signs of nasal and ocular discharge, facial deformity, and stertorous breathing. Median duration of signs prior to diagnosis was 3 months and 95% of the dogs had been given treatment prior to definitive diagnosis. All 49 tumors were malignant; 27 were classified histologically as carcinomas and 22 were sarcomas. Nineteen dogs were treated, using surgery alone or in combination with radiation therapy. Median survival duration was 5 months (mean 6.7 mo).


A family with two cases of melanocytic tumors and fragile X syndrome.
Fragile X syndrome (FXS), a leading cause of inherited intellectual disability, most commonly results from an expansion of the CGG trinucleotide repeat in the fragile X mental retardation 1 (FMR1) gene to more than 200 copies (full mutation). The FXS phenotype differs by sex and is associated with intellectual and cognitive impairment, characteristic physical features, epilepsy, and/or behavioral challenges including autism spectrum disorder. In this patient population, tumors involving blood cells, digestive organs, the central nervous system, and testes have been described, but melanocytic tumors have not been reported. Here, we describe two maternal cousins with FXS, one of whom has melanoma and the other has atypical nevus syndrome. We discuss possible mechanisms leading to this unusual or possibly coincidental association and the difficulties in the optimal treatment of FXS patients.


Exploring the effects of verb and noun treatment on verb phrase production in primary progressive aphasia: A series of single case experimental design studies.
Evidence of generalization to connected speech following lexical retrieval treatment in Primary Progressive Aphasia (PPA) is scarce. Consequently, this study systematically investigated changes in verb phrase production following lexical retrieval treatment in a series of single case experimental design studies. Four individuals with PPA (three semantic- and one logopenic variant PPA) who had previously demonstrated that they could integrate verbs and nouns into sentence structures in a cueing paradigm, undertook a sequence of verb and noun lexical retrieval treatments using Repetition and Reading in the Presence of a Picture. Production of treated nouns- and/or verbs-in-isolation significantly improved following treatment for three of the four participants. Verb phrase production did not improve for one of these participants (logopenic PPA), perhaps due to the relatively small treatment dose. Two participants (semantic variant PPA) did, however, demonstrate across-level generalization, with improvement in treated verbs and using those verbs in (untreated) verb phrases. Their verb phrase production improved most after lexical retrieval treatment for both nouns and verbs, suggesting this combined approach may benefit across-level generalization for some individuals in clinical practice.


What makes a good clinical teacher in medicine? A review of the literature.
The authors perform a review of the literature pertinent to the question, "What makes a good clinical teacher in medicine?" After framing the question, based on discussions of their own experiences with clinical teachers, the authors performed a search of the literature pertinent to the question, "What are the qualities of a good clinical teacher in medicine?" Between July and December, 2006, they reviewed titles from Index Medicus (1909-1966), PubMed (1966 to the present), PubMed Related Articles, and referenced articles. The initial selections were chosen by scanning pre-1966 Index Medicus title lists and post-1966 abstracts. Chosen articles were then read in their entirety, and those which described specific characteristics of clinical teachers were selected for inclusion. Qualitative analysis was used to identify themes. From 4,914 titles, 68 articles were selected for analysis-26 published before 1966, and 42 published after 1966. Four hundred eighty descriptors were identified and grouped into 49 themes, which were clustered into three main categories: physician, teacher, and human characteristics. Echoing the authors' intuitive descriptions, noncognitive characteristics dominated the descriptions and themes. Excellent clinical teaching, although multifactorial, transcends ordinary teaching and is characterized by inspiring, supporting, actively involving, and communicating with students. Faculty development programs and future research should focus on development of the noncognitive attributes of clinical teachers, as well as the knowledge and skills associated with effective teaching.


Cross-talk between bacterial two-component systems drives stepwise regulation of flagellar biosynthesis in swarming development.
Swarming motility is a mode of bacterial movement over a solid surface driven by rotating flagella in a coordinated manner. Bacteria can use two-component system (TCS), which typically comprises a sensor kinase and a specific cognate response regulator, to properly react to environmental changes. We previously showed that the TCS RssAB suppresses flagellar biosynthesis master regulator flhDC specifically in swarming lag phase to control surface migration timing without affecting expansion rate in Serratia marcescens swarming development. Here we demonstrate that the TCS QseBC, which has been found in several human pathogens involved in flagellar and virulence regulation, has cross-talk with RssAB. We demonstrate that the phosphorylated QseB repressed flhDC expression, reducing swarming migration rate with modest effect on migration initiation. Unexpectedly, the QseC can dephosphorylate non-cognate response regulator RssB. Deletion of qseC prolonged RssAB signaling, reduced flhDC expression, and delayed migration initiation. Our data suggest that QseC is a flagellar biosynthesis activator by de-repressing RssB ∼ P and QseB ∼ P respectively in lag and migration phases in a stage-specific manner in swarming development.


β Cell dysfunction during progression of metabolic syndrome to type 2 diabetes.
In a society where physical activity is limited and food supply is abundant, metabolic diseases are becoming a serious epidemic. Metabolic syndrome (MetS) represents a cluster of metabolically related symptoms such as obesity, hypertension, dyslipidemia, and carbohydrate intolerance, and significantly increases type 2 diabetes mellitus risk. Insulin resistance and hyperinsulinemia are consistent characteristics of MetS, but which of these features is the initiating insult is still widely debated. Regardless, both of these conditions trigger adverse responses from the pancreatic β cell, which is responsible for producing, storing, and releasing insulin to maintain glucose homeostasis. The observation that the degree of β cell dysfunction correlates with the severity of MetS highlights the need to better understand β cell dysfunction in the development of MetS. This Review focuses on the current understanding from rodent and human studies of the progression of β cell responses during the development of MetS, as well as recent findings addressing the complexity of β cell identity and heterogeneity within the islet during disease progression. The differential responses observed in β cells together with the heterogeneity in disease phenotypes within the patient population emphasize the need to better understand the mechanisms behind β cell adaptation, identity, and dysfunction in MetS.


Next of kin perspectives on the experience of end-of-life care in a community setting.
Previous studies of end-of-life experience have been conducted primarily in urban medical centers and mostly focused on preferences for rather than experience of care. To describe family end-of-life experience and perceptions of care across clinical settings from a semirural community perspective, identifying experiences associated with patient quality of life as rated by next of kin. Retrospective study using structured interviews with decedents' next of kin and medical chart reviews. Two hundred seven nonsudden deaths (24 hours of medical care immediately prior to death) in Missoula County, Montana, in 1996-1997. Family respondents rated quality of life for decedents at lifes's end on a 0-10 scale and were grouped according to their rating as good, moderate, or poor quality of life. Significant differences between groups were found for five elements of experience: severity and frequency of pain and other symptoms; ratings of pain management; adherence to care preferences; life enrichment activities; and communication between and among patients, family members, and professional caregivers. Higher family ratings were associated with a member of the health care team being responsible for the patient receiving the best care possible, and having someone familiar with the patient and family available nights and weekends. Opportunities exist in community health care settings to improve quality of life for people approaching life's end. Clinicians, patients, and patients' families can contribute by engaging in open and ongoing communication about preferences for care, symptoms and their management, activities designed to enrich patients' personal experiences, as well as having patient care coordination and continuity of care on nights and weekends.


Clinical validation of fiberoptic immunobiosensor for point-of-care analysis of plasma nerve growth factor.
Upregulation of plasma nerve growth factor (NGF) is indicative of cardiac nerve sprouting that is underlying the mechanisms for cardiac arrhythmias. A conventional assay method (e.g., enzyme-linked immunosorbent assay [ELISA]) is usually time consuming and technically complicated for NGF analysis for potential arrhythmia prognosis. This study is to develop a rapid and and reliable assay method for point-of-care (POC) testing of plasma NGF. We recently developed a fiberoptic immunobiosensor for point-of-care testing of human plasma NGF. Physiological concentrations of NGF (1 to 200 ng/ml) could be quantified in both buffer and human blood plasma samples (100 microl) within 5 min. The intra-assay coefficient of variation was 5%, and the interassay coefficient of variation was 8%. The clinical utility of the NGF biosensor was evaluated using clinical blood samples from atrial fibrillation patients (n = 21). Peripheral venous blood was sampled before and immediately after radiofrequency ablation and again at postoperative day 1. The NGF level did not change significantly between before (15.73 +/- 16.67 ng/ml) and immediately after radiofrequency ablation (13.58 +/- 11.45 ng/ml, P = NS); however, there was a significant elevation to 28.41 +/- 19.52 ng/ml in postoperative day 1 (P <.01). In a follow-up study (11 +/- 1 months), the increased magnitude in patients with atrial fibrillation recurrence (4.1-fold +/- 1.96-fold) was significantly higher than those without (1.72-fold +/- 0.53-fold; P <.001). The results were highly comparable to those of the ELISA analysis. Because of the comparable data accuracy and much faster assay time as compared with ELISA, the fiberoptic biosensor is promising as a clinical POC assay method for plasma NGF analysis at patient bedsides for potential cardiac disease diagnosis and prognosis.


Screen Printing to Create 3D Tissue Models.
3D printing has revolutionized making tissue models, but the instruments are often quite expensive, and the approach can involve heat and/or shear forces that can damage cells. As a complement to more traditional 3D printing approaches, we looked at screen printing. Screen printing is an additive manufacturing technique used to pattern inks through screens supporting patterns onto different surfaces. It has a wide range of applications ranging from traditional printing to printing electric circuit boards. Taking cues from this we have developed a process of screen printing live cells along with a suitable scaffold on to different surfaces to generate in vitro models. The process is not only inexpensive and simple to use, but it also offers a wide range of advantages like the ability to use a range of bioinks limited only by their gelation time, printing on different surfaces, and the ability to autoclave all of the major components. In this paper, we present the screen assembly and the setup we used to print the cells along with the resolution and limits of features printed and the effect of the printing on the cells.


Exploring the contribution of case study research to the evidence base for occupational therapy practice: a scoping review protocol.
This scoping review will explore the range and characteristics of case study research within the occupational therapy evidence base. It will examine how case study research is defined, the methodologies adopted, and the context in which it is applied. Most importantly, it will consider the viability of case study research for contributing to the evidence base for occupation and health. Occupational therapists report barriers to conducting research due to the complexities of clinical practice, and lack of knowledge, time, and resources. Case study research is generating interest as a potentially manageable and practical solution to increase research engagement. However, it is not clear how this is being utilized by occupational therapists or how feasible it is to contribute to the evidence base. Opinion, text, and empirical studies that explicitly use or discuss case study research methodology within an occupational therapy context will be included. Studies will be excluded where the occupational therapy context cannot be clearly defined, for example, where they are multi-disciplinary focused or where a case study research design is not explicit (eg, a descriptive case report without data collection). All countries and practice settings will be included. A three-step search following JBI methodology will be conducted across databases and websites for English-language, published peer-reviewed and gray literature from 1990. Study selection will be completed by two independent reviewers. A data extraction table developed and piloted by the authors will be used and data charted to align with the research questions.


A phase I dose-finding study of silybin phosphatidylcholine (milk thistle) in patients with advanced hepatocellular carcinoma.
To determine the maximum tolerated dose per day of silybin phosphatidylcholine (Siliphos) in patients with advanced hepatocellular carcinoma (HCC) and hepatic dysfunction. Patients with advanced HCC not eligible for other therapies based on poor hepatic function were enrolled in a phase I study of silybin phosphatidylcholine. A standard phase I design was used with 4 planned cohorts, dose escalating from 2, 4, 8, to 12 g per day in divided doses for 12 weeks. Three participants enrolled in this single institution trial. All enrolled subjects consumed 2 g per day of study agent in divided doses. Serum concentrations of silibinin and silibinin glucuronide increased within 1 to 3 weeks. In all 3 patients, liver function abnormalities and tumor marker α-fetoprotein progressed, but after day 56 the third patient showed some improvement in liver function abnormalities and inflammatory biomarkers. All 3 participants died within 23 to 69 days of enrolling into the trial, likely from hepatic failure, but it could not be ruled out that deaths were possibly due to the study drug. Short-term administration of silybin phosphatidylcholine in patients with advanced HCC resulted in detectable increases in silibinin and its metabolite, silibinin glucuronide. The maximum tolerated dose could not be established. Since patients died soon after enrollment, this patient population may have been too ill to benefit from an intervention designed to improve liver function tests.


Occupational health problems among agricultural and plantation workers.
Agricultural and plantation works are associated with a variety of unique occupational health hazards in the form of physical factors like extreme weather conditions, sunrays, etc; chemicaVtoxicological hazards in the form of pesticides/fertilisers, etc, including different forms of biological and mechanical hazards. As most of our rural people are engaged in varied types of agricultural activities, they are highly susceptible for suffering from numerous work related health disorders. There are very few data regarding the epidemiology of occupational health disorders among agricultural and plantation workers. Clinically well recognised group of occupationally acquired health problems may be respiratory, dermatological, traumatic, poisoning and neoplastic in nature. Prevalence of some specific zoonotic diseases and behavioural health problems are also found to be more among them. There is lack of attention for prevention and control of these occupational health problems. An adequately developed comprehensive occupational health care programme having all the components of preventive, curative and rehabilitative aspects can only promote and maintain the highest degree of physical, mental and social well-being in all types of agricultural and plantation workers of rural India.


Secretion and degradation of insulin and glucagon in carbon tetrachloride-induced liver injury rats.
To elucidate the mechanism of hyperinsulinemia and hyperglucagonemia in liver diseases, secretion of insulin and glucagon from perfused pancreas and extraction of insulin and glucagon by perfused liver were investigated in carbon tetrachloride inhalated liver injury rats. Fasting plasma insulin and glucagon levels and insulin and glucagon levels after arginine injection (0.25 g/kg) in liver injury rats were significantly higher than those in control rats. Glucagon levels after glucose injection (0.5 g/kg) were slightly increased in the liver injury group. Insulin responses to 16.7 mM glucose and 10 mM arginine from perfused pancreas were similar in liver injury rats and control rats. Glucagon response to 10 mM arginine from perfused pancreas was also similar in liver injury rats and control rats. Insulin extraction by perfused liver in liver injury rats (45 +/- 9%) was significantly (P less than 0.05) lower than that (64 +/- 11%) in control rats, and glucagon extraction by perfused liver was also significantly (P less than 0.05) decreased in liver injury rats (57 +/- 8%) compared with controls (73 +/- 9%). It is concluded that in carbon tetrachloride-induced liver injury rats, hyperinsulinemia and hyperglucagonemia may be dependent on decreased insulin and glucagon extraction by the liver.


Stage of change and motivation to healthy diet and habitual physical activity in type 2 diabetes.
Lifestyle changes to healthy diet (HD) and habitual physical activity (HPA) are recommended in type 2 diabetes mellitus (T2DM). Yet, for most people with diabetes, it may be difficult to start changing. We investigated the stage of change toward healthier lifestyles according to Prochaska's model, and the associated psychological factors in T2DM patients, as a prerequisite to improve strategies to implement behavior changes in the population. A total of 1,353 consecutive outpatients with T2DM attending 14 tertiary centers for diabetes treatment completed the validated EMME-3 questionnaire, consisting of two parallel sets of instruments to define the stage of change for HD and HPA, respectively. Logistic regression was used to determine the factors associated with stages that may hinder behavioral changes. A stage of change favoring progress to healthier behaviors was more common in the area of HD than in HPA, with higher scores in action and maintenance. Differences were observed in relation to gender, age and duration of disease. After adjustment for confounders, resistance to change toward HD was associated with higher body mass index (BMI) (odds ratio (OR) 1.05; 95 % confidence interval (CI) 1.02-1.08). Resistance to improve HPA also increased with BMI (OR 1.06; 95 % CI 1.03-1.10) and decreased with education level (OR 0.74; 95 % CI 0.64-0.92). Changing lifestyle, particularly in the area of HPA, is not perceived as an essential part of treatment by many subjects with T2DM. This evidence must be considered when planning behavioral programs, and specific interventions are needed to promote adherence to HPA.


Cardinal interpolation.
A Bayesian probability density for an interpolating function is developed, and its desirable properties and practical potential are demonstrated. This density has an often needed but previously unachieved property, here called cardinal interpolation, which ensures extrapolation to the density of the least squares linear model. In particular, the mean of the cardinal interpolation density is a smooth function that intersects given (x, y) points and which extrapolates to their least squares line, and the variance of this density is a smooth function that is zero at the point x values, that increases with distance from the nearest point x value, and that extrapolates to the well-known quadratic variance function for the least squares line. The new cardinal interpolation density is developed for Gaussian radial basis interpolators using fully Bayesian methods that optimize interpolator smoothness. This optimization determines the basis function widths and yields an interpolating density that is non-Gaussian except for large magnitude x and which is therefore not the outcome of a Gaussian process. Further new development shows that the salient property of extrapolation to the density of the least squares linear model can be achieved for more general approximating (not just interpolating) functions.


Lung Cancer Survival Among Chinese Americans, 2000 to 2010.
Despite being the leading cause of cancer death, no prior studies have characterized survival patterns among Chinese Americans diagnosed with lung cancer. This study was conducted to identify factors associated with survival after lung cancer in a contemporary cohort of Chinese patients with lung cancer. The study design is a prospective descriptive analysis of population-based California Cancer Registry data. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) for overall mortality. Participants were Chinese American residents diagnosed with first primary invasive lung cancer from 2000 to 2010 (2,216 men and 1,616 women). Among Chinese men, decreased mortality was associated with care at a National Cancer Institute cancer center (HR, 0.85; 95% CI, 0.73 to 0.99) and adenocarcinoma versus small-cell carcinoma (HR, 0.78; 95% CI, 0.65 to 0.92). Women had better survival compared with men (HR, 0.82; 95% CI, 0.75 to 0.89), with mortality associated with never married versus currently married status (HR, 1.36; 95% CI, 1.11 to 1.66), lower versus higher neighborhood socioeconomic status (HR, 1.38; 95% CI, 1.10 to 1.72 comparing lowest to highest quintile), care at a cancer center (HR, 0.80; 95% CI, 0.67 to 0.96), and squamous cell relative to small-cell carcinoma (HR, 1.60; 95% CI, 1.04 to 2.48). Focusing on factors associated with marital status, community socioeconomic status, and characteristics unique to National Cancer Institute-designated cancer centers may help to identify potential strategies for improving the length of survival for Chinese Americans.


Clinical Presentation and Multifactorial Pathogenesis of Necrotizing Enterocolitis in the Preterm Infant.
Necrotizing enterocolitis (NEC) is a serious infection of the bowel wall induced by multiple pathological factors, which include inflammation and tissue invasion with bacteria known to cause severe infections. NEC is now understood to be several disease processes under one umbrella. The most common form occurs in premature infants and can exert significant impacts to preterm morbidity and mortality. This narrative review describes current knowledge of the clinical presentation and pathophysiology of NEC in premature infants. A review of literature was conducted using key words in PubMed and CINAHL with preference for years 2015 to 2020. Several converging and interrelated factors including characteristics of the premature intestinal mucosa, gut ischemia, dysregulation of the microbiome, enteral feeding, and genetics create an environment where NEC is more likely to occur. To recognize and diagnose NEC in preterm infants, an understanding of underlying factors that create an optimal environment for disease acquisition in premature infants is essential. Prevention of NEC remains the most important strategy for decreasing morbidity and mortality. Multiple areas of potential study exist for NEC pathophysiology including those that consider how the factors discussed in this review are interrelated and how each particular pathway can be optimized to prevent the onset of NEC.


The phosphodiesterase inhibitor, ibudilast, attenuates neuroinflammation in the MPTP model of Parkinson's disease.
Since the degeneration of the nigrostriatal dopaminergic pathway in Parkinson's disease (PD) is associated with the inflammation process and decreased levels of cyclic nucleotides, inhibition of up-regulated cyclic nucleotide phosphodiesterases (PDEs) appears to be a promising therapeutic strategy. We used ibudilast (IBD), a non-selective PDE3,4,10,11 inhibitor, due to the abundant PDE 4 and 10 expression in the striatum. The present study for the first time examined the efficacy of IBD in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. IBD [0, 20, 30, 40, or 50 mg/kg] was injected b.i.d. subcutaneously for nine days to three-month-old male C57Bl/10Tar mice, beginning two days prior to MPTP (60 mg/kg) intoxication. High-pressure liquid chromatography, Western blot analysis, and real time RT-PCR methods were applied. Our study demonstrated that chronic administration of IBD attenuated astroglial reactivity and increased glial cell-derived neurotrophic factor (GDNF) production in the striatum. Moreover, IBD reduced TNF-α, IL-6, and IL-1β expression. IBD had a well-defined effect on astroglial activation in the mouse model of PD; however, there was no protective effect in the acute phase of injury. Diminished inflammation and an increased level of GDNF may provide a better outcome in the later stages of neurodegeneration.


Identification of a major quantitative trait locus for ear size induced by space flight in sweet corn.
The development of molecular markers has contributed to progress in identifying the gene(s) responsible for favorable variations in maize studies. In this study, quantitative trait locus (QTL) mapping was conducted using simple sequence repeat markers in an F2 sweet corn population from a cross between parental line 1132 and space flight-induced mutant line 751 to identify the loci contributing to an increase in some yield traits. A primary mutated genomic region was located on chromosome 9. In total, 26 QTL were detected for eight yield-related traits and assembled into three clusters on chromosome 9. The largest QTL cluster at bin 9.02/03, primarily contributing to >10% of the phenotypic variation in ear and cob diameters, was likely due to a major QTL. Desired alleles of these QTL were provided by the mutant line 751. The primary action of the major mutant allele was an additive effect. Another mutant locus, which was induced in bin 9.01, increased cob and ear diameters by dominant genetic action.


The orally administered P-glycoprotein inhibitor R101933 does not alter the plasma pharmacokinetics of docetaxel.
This Phase I study was performed to assess the feasibility of combining docetaxel with the new P-glycoprotein inhibitor R101933 and to determine the dose limiting toxicity of this combination. Fifteen patients received oral R101933 alone at a dose escalated from 200 to 300 mg twice daily (b.i.d.; cycle 0), an escalating i.v. dose of docetaxel (60, 75, and 100 mg/m2) as a 1-h infusion (cycle 1), and the combination (cycle 2 and further). Dose limiting toxicity consisting of mucositis and neutropenic fever was reached at the combination of docetaxel, 100 mg/m2, and R101933, 300 mg b.i.d., and the maximum tolerated dose was established at docetaxel, 100 mg/m2, and R101933, 200 mg b.i.d. Plasma concentrations of R101933 achieved in patients were in the same range as required in preclinical rodent models to overcome paclitaxel resistance. The plasma pharmacokinetics of docetaxel were not influenced by the R101933 regimen at any dose level tested, as indicated by plasma clearance values of 26.5 +/- 7.78 liters/h/m2 and 23.4 +/- 4.52 liters/h/m2 (P = 0.15) in cycles 1 and 2, respectively. These findings indicate that the contribution of a P-glycoprotein inhibitor to the activity of anticancer chemotherapy can now be assessed in patients for the first time independent of its effect on drug pharmacokinetics.


Novel product chemistry from mechanistic analysis of ent-copalyl diphosphate synthases from plant hormone biosynthesis.
An active-site water molecule coordinated by conserved histidine and asparagine residues seems to serve as the catalytic base in all ent-copalyl diphosphate synthases (CPSs). When these residues are substituted by alanine, the mutant CPSs produce stereochemically novel ent-8-hydroxy-CPP. Given the requisite presence of CPSs in all land plants for gibberellin phytohormone biosynthesis, such plasticity presumably underlies the observed extensive diversification of the resulting labdane-related diterpenoids.


Isospora tiaris n.sp. (Apicomplexa: Eimeriidae) from the sooty grassquit (Tiaris fuliginosa), a passeriform bird of South America.
Isospora tiaris n. sp. is described from the feces of an adult bird, a sooty grassquit (Tiaris fuliginosa) from Venezuela. The oocysts are subspherical, 27.1 x 23.8 (24.7-30.0 x 21.2-26.5) microns with a bilayered, smooth, colorless wall. A micropyle and oocyst residuum are absent; an ellipsoidal polar granule is usually present. Sporocysts are ovoidal, 14.7 x 10.8 (12.4-16.8 x 8.8-12.4) microns with prominent Stieda and substieda bodies and a residuum composed of small uniform granules.


Zinc bioglasses regulate mineralization in human dental pulp stem cells.
A promising strategy in regenerative endodontics is the combination of human dental pulp stem cells (hDPSCs) with an appropriate biomaterial substrate. The effects of zinc and zinc containing bioactive glasses (ZnBGs) on hDPSCs have been characterized in this study. ZnBGs were designed and produced. Then the odontogenic differentiation and mineralization potential of hDPSCs upon ZnBGs treatment were investigated. Free Zn ions (0-5ppm) enhanced proliferation and alkaline phosphatase (ALP) activity of hDPSCs. Further, ZnBGs conditioned medium (ZnBG-CM) increased the production and secretion of odontogenic markers: dentin sialophosphoprotein (DSPP), dentin matrix protein 1 (DMP-1). In addition, we identified that mRNA expression of the osteogenic markers RUNX2, OCN, BSP, BMP-2, MEPE and ON was increased following treatment with ZnBG-CM. Long term treatment with ZnBG-CM increases the formation rate of mineralized nodules (similar to hydroxyapatite, Ca:P=1.6), as confirmed by scanning electron microscopy combined with energy dispersive X-ray spectroscopy (SEM-EDX). Lastly, the administration of ZnBG-CM induces VEGF expression. These findings implicate that ZnBG would be beneficial in regenerative endodontics and could influence the way present Zn containing clinical products are used.


Estimating the time of onset of testicular torsion using ultrasonography in an experimental rat model.
We aimed to document the time of onset of ultrasonographic and histologic changes in the testes of a rat model following testicular torsion. Twenty-five Sprague-Dawley rats were divided into four groups. All animals underwent preoperative Doppler ultrasonography. Groups 1, 2, and 3 underwent unilateral surgical torsion of the testis lasting for 72, 24, and 6 hours, respectively. Group 4 underwent a sham operation. The animals were followed with Doppler ultrasonography at 6, 24, 48, and 72 hours postoperatively. Histologic examinations were performed at the designated final time point for each group. After torsion, enlargement of the epididymal head and thickening of the spermatic cord over time were noted. Based on the ultrasonographic dimensions, the ratio of the epididymal volume increased with time following torsion (p=0.002). The torsed testes had an average weight gain of 0.27 g at 6 hours compared to the control testes, but an average weight loss of 0.22 g at 72 hours (P=0.006). Changes in testicular echotexture were noted as soon as 6 hours after torsion, but there was no consistent pattern of echotexture change thereafter. Histologically, viable tubules were seen 6 hours after torsion, while extensive hemorrhagic necrosis was found at 72 hours. In evaluating testicular torsion, the enlargement ratio of the epididymis and thickening of the spermatic cord on Doppler ultrasonography may be useful for determining the urgency of immediate surgery. Changes in testicular echotexture may not be a reliable indicator of the time of onset.


Challenges and barriers for implementation of the World Health Organization Global Disability Action Plan in low- and middle- income countries.
To identify potential barriers and facilitators for implementation of the World Health Organization Global Disability Action Plan (GDAP) in Nigeria and compare these with other low- and middle-income countries. A rehabilitation team from the Royal Melbourne Hospital, Parkville, Australia, conducted intensive workshops at medical/academic institutions in Nigeria for healthcare professionals from various local Physical Medicine and Rehabilitation facilities. A modified Delphi method identified challenges for person with disability, using 3 GDAP objectives. Findings were compared with similar exercises in Madagascar, Pakistan and Mongolia. Despite differences in the healthcare system and practice, the challenges reported in Nigeria were similar to those in other 3 low- and middle-income countries, at both macro (governmental/policymakers) and micro levels (community/social/individual). Common challenges identified were: limited knowledge of disability services, limited Physical Medicine and Rehabilitation workforce, guidelines and accreditation standards; coordination amongst healthcare sectors; social issues; data and research; legislation and political commitment. Common potential facilitators included: need for strong leadership; advocacy of disability-inclusive development; investment in infrastructure/human resources; coordination/partnerships in healthcare sector; and research. Disability care is an emerging priority in low- and middle-income countries to address the needs of people with disability. The challenges identified in Nigeria are common to most low- and middle-income countries. The GDAP framework can facilitate access and strengthen Physical Medicine and Rehabilitation services.


An Examination of the Joint Effect of the Social Environment and Air Pollution on Dementia Among US Older Adults.
Evidence suggests exposure to air pollution increases the risk of dementia. Cognitively stimulating activities and social interactions, made available through the social environment, may slow cognitive decline. We examined whether the social environment buffers the adverse effect of air pollution on dementia in a cohort of older adults. This study draws from the Ginkgo Evaluation of Memory Study. Participants aged 75 years and older were enrolled between 2000 and 2002 and evaluated for dementia semi-annually through 2008. Long-term exposure to particulate matter and nitrogen dioxide was assigned from spatial and spatiotemporal models. Census tract-level measures of the social environment and individual measures of social activity were used as measures of the social environment. We generated Cox proportional hazard models with census tract as a random effect and adjusted for demographic and study visit characteristics. Relative excess risk due to interaction was estimated as a qualitative measure of additive interaction. This study included 2,564 individuals. We observed associations between increased risk of dementia and fine particulate matter (µg/m3), coarse particulate matter (µg/m3), and nitrogen dioxide (ppb); HRs per 5 unit increase were 1.55 (1.01, 2.18), 1.31 (1.07, 1.60), and 1.18 (1.02, 1.37), respectively. We found no evidence of additive interaction between air pollution and the neighborhood social environment. We found no consistent evidence to suggest a synergistic effect between exposure to air pollution and measures of the social environment. Given the many qualities of the social environment that may reduce dementia pathology, further examination is encouraged.


Pathobiology of Avian avulavirus 1: special focus on waterfowl.
Avian avulaviruses serotype 1 (abbreviated as APMV-1 for the historical name avian paramyxovirus 1) are capable of infecting a wide spectrum of avian species with variable clinical symptoms and outcomes. Ease of transmission has allowed the virus to spread worldwide with varying degrees of virulence depending upon the virus strain and host species. The emergence of new virulent genotypes from global epizootics, and the year-to-year genomic changes in low and high virulence APMV-1 imply that distinct genotypes of APMV-1 are simultaneously evolving at different geographic locations across the globe. This vast genomic diversity may be favoured by large variety of avian species susceptibility to APMV-1 infection, and by the availability of highly mobile wild birds. It has long been considered that waterfowls are not sensitive to APMV-1 and are unable to show any clinical signs, however, outbreaks from the 90's contradict these concepts. The APMV-1 isolates are increasingly reported from the waterfowl. Waterfowl have strong innate immune responses, which minimize the impact of virus infection, however, are unable to prevent the viral shedding. Numerous APMV-1 are carried by domestic waterfowl intermingling with terrestrial poultry. Therefore, commercial ducks and geese should be vaccinated against APMV-1 to minimize the virus shedding and for the prevention the transmission. Genetic diversity within APMV-1 demonstrates the need for continual monitoring of viral evolution and periodic updates of vaccine seed-strains to achieve efficient control and eradication of APMV-1 in waterfowls.


New developments in mesothelial pathology.
This review article examines some new and some problem areas in mesothelial pathology, four of which are discussed, as follows. (1) The concept of mesothelioma in situ: this lesion is defined as a single layer of bland mesothelial cells without evidence of invasion, but that have lost BAP1 and/or MTAP by immunohistochemistry. Benign reactions can exactly mimic mesothelioma in situ, but a hint to the correct diagnosis is a story of recurrent pleural effusions/ascites of unknown aetiology without radiological or direct visual evidence of tumour. (2) The nature of well-differentiated papillary mesothelial tumour (WDPMT): WDPMT has a long history of arguments regarding its behaviour, and this uncertainty can now be seen to arise, in part, from the observation that some forms of mesothelioma in situ microscopically look exactly like WDPMT. Hence, it is recommended to always run at least a BAP1 stain on any lesion that looks like WDPMT. Both flat and WDPMT-like mesothelioma in situ are strongly associated with eventual development of invasive mesothelioma, but this process is relatively slow. (3) New immunostains for separating mesothelioma from other tumours: here, it is proposed that in most cases, and particularly when the differential is epithelioid mesothelioma versus non-small cell lung cancer, one can make this separation with extremely high sensitivity and specificity using just two stains: HEG1 and claudin-4. (4) Markers for separating benign from malignant mesothelial proliferations: this topic is briefly reviewed, with an indication of which markers are generally accepted and the best utilisation and possible limitations of each marker.


Virulence of iron transport mutants of Shigella flexneri and utilization of host iron compounds.
Mutants of Shigella flexneri defective in aerobactin-mediated iron transport were assayed for virulence in several model systems. A Tn5 insertion mutant was invasive in HeLa cells, lethal in the chicken embryo, and produced keratoconjunctivitis in the guinea pig, indicating little or no loss of ability to invade and multiply intracellularly. Although the mutant failed to grow in low-iron medium in vitro, growth equivalent to that of the wild type was observed in HeLa cell lysates. Thus, there appears to be sufficient available iron inside the HeLa cell to allow growth in the absence of siderophore synthesis. Possible host iron sources were tested, and both the mutant and wild type utilized hemin or hematin as a sole source of iron. Only the wild-type, aerobactin-producing strain could remove iron from transferrin or lactoferrin. Two deletion mutants were also assayed for virulence and were found to be avirulent for the chicken embryo. These deletions encompass flanking sequences as well as the aerobactin genes; therefore, adjacent genes may be required for virulence.


Light-Colored Maillard Peptides: Formation from Reduced Fluorescent Precursors of Browning and Enhancement of Saltiness Perception.
The browning formation and taste enhancement of peptides derived from soybean, peanut, and corn were studied in the light-colored Maillard reaction compared with the deep-colored reaction. The fluorescent compounds, as the browning precursors, were accumulated during the early Maillard reaction of peptides and subsequently degraded into dark substances, which resulted in a higher browning degree of deep-colored Maillard peptides (MPs), especially for the MPs derived from corn peptide. However, the addition of l-cysteine in light-colored Maillard reaction reduced the formation of deoxyosones and short-chain reactive α-dicarbonyls, thereby weakening the generation of fluorescent compounds and inhibited the browning of MPs. Synchronously, the peptides were thermally degraded into small peptides and amino acids, which were consumed less during light-colored thermal reaction due to its shorter reaction time at high temperature compared with deep-colored ones, thus contributing to a stronger saltiness perception of light-colored MPs than deep-colored MPs. Besides, the Maillard reaction products derived from soybean and peanut peptides possessed an obvious "kokumi" taste, making them suitable for enhancing the soup flavors.


The value to nursing research of Gadamer's hermeneutic philosophy.
In recent years there has been an increasing awareness in nursing research of the importance of accumulation of knowledge related particularly to the art of nursing. Because of this, nurses are endeavouring to understand more comprehensively the meanings given to central phenomena such as caring, comfort and reassurance, and also to research them with methodologies in such a way that these meanings are not destroyed, distorted or decontextualized. Gadamer's hermeneutic philosophy may prove to be a valuable approach in enabling nurses to gain a deeper and fuller understanding of these phenomena which are central to nursing practice.


[Spontaneous spleen rupture associated to active cytomegalovirus infection].
We present a 24 year old immunocompetent male who developed a spontaneous rupture of the spleen (SRE) during an acute cytomegalovirus (CMV) infection. The only previous clinical feature was the presence of flu-like symptoms two weeks before the SRE. The diagnosis was confirmed by the presence of IgM antibodies to CMV in the serum and a positive CMV-PCR in the splenic biopsy after splenectomy. The patient recovered completely after surgery. Spontaneous splenic rupture is an uncommon event associated with primary cytomegalovirus infection, and this is the first case reported in our country.


An examination of the validity of the IHS classification system for migraine and tension-type headache in the college student population.
The validity of the International Headache Society (IHS) classification system for college-aged students with headache was examined using cluster analysis. Undergraduate college student volunteers (N = 369) underwent a structured diagnostic interview for headaches, and the sample was divided into two subsamples for purposes of replication. A hierarchical cluster analysis (Ward's method) of the headache characteristics reported by the first subsample suggested a statistically distinct three-cluster solution, and the solution was replicated using the second subsample. It appeared that one cluster was tensionlike, while the other two were migrainelike. Nonhierarchical cluster analyses (K-means) of the cases from each subsample revealed a similar pattern of a tensionlike and two migrainelike clusters. Identical three-cluster solutions were found for the second subsample both by using cluster centers from the first subsample and by clustering the cases independently, suggesting that the cluster solution was not a random finding. The IHS classification system appears to lack adequate specificity and sensitivity for college-aged students with headache who report migrainelike symptoms. Thus, the generalizability of research results using college-aged students with headache to the adult population may be questionable.


Failure of elevated heat shock protein 70 antibodies to alter cochlear function in mice.
Heat shock protein 70 (HSP70) has been suggested as the putative cochlear antigen underlying a proposed autoimmune etiology in certain cases of Meniere's disease and idiopathic hearing loss. To determine if antibodies to this cellular protein are capable of altering cochlear function, BALB/c (N= 3) and CBA/J (N= 9) mice were inoculated with bovine HSP70 by intraperitoneal injections (10 microg in saline) every 10 days for 7 or 10 months, respectively. An equal number of control mice were injected with PBS according to the same schedule. ABR thresholds at 4, 8, 16, and 32 kHz in the HSP70-inoculated mice did not change over the 10 month period and were similar to saline controls. Furthermore, serum immune complexes and antinuclear antibodies did not increase over the inoculation period. ELISA analysis demonstrated the mice created antibodies to the foreign HSP70, but these apparently caused no abnormalities in the auditory or immune systems. It was concluded that foreign HSP70 is antigenic and inoculation with it will raise antibodies, but these antibodies were neither immunopathogenic nor cochleopathic. Therefore, these findings do not support current theories that elevated anti-HSP70 antibodies are the underlying cause of hearing loss in patients with such antibodies present.


A variant NuRD complex containing PWWP2A/B excludes MBD2/3 to regulate transcription at active genes.
Transcriptional regulation by chromatin is a highly dynamic process directed through the recruitment and coordinated action of epigenetic modifiers and readers of these modifications. Using an unbiased proteomic approach to find interactors of H3K36me3, a modification enriched on active chromatin, here we identify PWWP2A and HDAC2 among the top interactors. PWWP2A and its paralog PWWP2B form a stable complex with NuRD subunits MTA1/2/3:HDAC1/2:RBBP4/7, but not with MBD2/3, p66α/β, and CHD3/4. PWWP2A competes with MBD3 for binding to MTA1, thus defining a new variant NuRD complex that is mutually exclusive with the MBD2/3 containing NuRD. In mESCs, PWWP2A/B is most enriched at highly transcribed genes. Loss of PWWP2A/B leads to increases in histone acetylation predominantly at highly expressed genes, accompanied by decreases in Pol II elongation. Collectively, these findings suggest a role for PWWP2A/B in regulating transcription through the fine-tuning of histone acetylation dynamics at actively transcribed genes.


Differences in microparticle release in patients with acute coronary syndrome and stable angina.
Microparticles (MP) are vesicles released from activated or apoptotic cells. Endothelial MP (EMP) are derived from injured endothelium, platelet MP (PMP) from activated platelets, and Annexin V positive MP (AMP) from apoptotic endothelial cells. The aim was to assess the release of MP and its association with inflammation and atherosclerotic burden. AMP, EMP and PMP were measured on admission (Day 0) in 33 patients with stable angina (SA) and 43 patients with acute coronary syndrome (ACS) undergoing percutaneous coronary interventions (PCI). In SA, peripheral artery disease (PAD) was assessed by ultrasound examination. In 30 of the 76 patients (20 ACS and 10 SA), MP, high-sensitivity-C-reactive protein (hs-CRP), and troponin T (TnT) levels were also assessed 24h (Day 1) and 48 h (Day 2) after PCI. AMP, EMP, and PMP were higher in ACS than in SA (all P<0.01). In the SA group, AMP, PMP, and EMP were similar in patients with or without PAD. In the ACS group, AMP increased until Day 2 (P=0.001), while EMP and PMP peaked on Day 1 (P<0.01) then decreased to baseline values. Day 2 AMP correlated with Day 2 TnT levels (r=0.43, P=0.01) while Day 1 EMP and PMP correlated with Day 1 hs-CRP (r=0.37, P=0.04 and r=0.33, P=0.05; respectively). Higher MP levels were observed in ACS than in SA. Atherosclerotic burden did not affect MP levels in stable patients.