An approach to rapidly identify the gender of the pigeon by using cross-priming amplification with immune-chromatographic strip.
Most birds are monomorphic species and breeds, which makes it difficult to determine their gender by appearances, especially the pigeon is a farm animal with economic interest in meat production, ornamentals, sports, and experimental animals. Until now, the available methods for determining the gender of pigeons have mainly consisted of endoscopy, laparoscopy, karyotyping, polymerase chain reaction (PCR), and other similar techniques. Nonetheless, these methods have notable limitations, such as high expenses, invasiveness, and time-consuming procedures, which hinder their practicality for efficiently determining the gender of pigeons. Therefore, an easy, accurate, sensitive, on-site, affordable, and applicable rapid identification of the gender of the pigeon is widely needed for the owner of the pigeon. The purpose of this study was to develop and evaluate the efficacy of Cross-priming amplification (CPA) combined with an immune-chromatographic strip (CPA-strip) for gender identification of the pigeon. The methodology was optimized through various experimental trials. Subsequently, ten samples collected from pigeons were subjected to analysis using the optimized CPA-strip assay, and the results indicated that all female samples were accurately detected. In contrast, the blood samples collected from chickens and ducks were negative when tested with the CPA-strip assay. In conclusion, our study demonstrates the successful establishment of an immune-chromatographic CPA-strip assay for the on-site gender determination of pigeons with high accuracy.


Protective properties of Huperzine A through activation Nrf2/ARE-mediated transcriptional response in X-rays radiation-induced NIH3T3 cells.
Huperzine A (HupA), derived from Huperzia Serrata, has exhibited a variety of biological actions, in particular neuroprotective effect. However, the protective activities of HupA on murine embryonic fibroblast NIH3T3 cells after X-rays radiation have not been fully elucidated. Herein, HupA treatment dramatically promoted cell viability, abated a G0/G1 peak accumulation, and ameliorated increase of cell apoptosis in NIH3T3 cells after X-rays radiation. Simultaneously, HupA notably enhanced activities of anti-oxidant enzymes, inhibited activity of lipid peroxide, and efficiently eliminated production of reactive oxygen species in NIH3T3 cells after X-rays radiation. Dose-dependent increase of antioxidant genes by HupA were associated with up-regulated Nrf2 and down-regulated Keap-1 expression, which was confirmed by increasing nuclear accumulation, and inhibiting of degradation of Nrf2. Notably, augmented luciferase activity of ARE may explained Nrf2/ARE-mediated signaling pathways behind HupA protective properties. Moreover, expression of Nrf2 HupA-mediated was significant attenuated by AKT inhibitor (LY294002), p38 MAPK inhibitor (SB202190) and ERK inhibitor (PD98059). Besides, HupA-mediated cell viability, and ROS production were dramatically bated by LY294002, SB202190, and PD98059. Taken together, HupA effectively ameliorated X-rays radiation-induced damage Nrf2-ARE-mediated transcriptional response via activation AKT, p38, and ERK signaling in NIH3T3 cells.


A prospective cohort study of late sequelae of pediatric allogeneic hematopoietic stem cell transplantation.
As survivors of pediatric allogeneic hematopoietic stem cell transplantations (HSCTs) increase in number, it is increasingly important to evaluate their well-being. We conducted this prospective cohort study to evaluate the cumulative incidence and risk factors for late sequelae of HSCT. Comprehensive surveillance tests were performed annually on every participant, regardless of signs and symptoms, to obtain accurate information on the time-of-onset of each late event to allow hazard function analyses. All participants included in this report had been followed for at least 3 years after HSCT. With a median follow-up of 9 years and a current age of 18.5 years, only 20 of the 155 participants (13%) had no late sequelae; 18 survivors (12%) had 1 chronic health condition, 71 (46%) had 2-4 conditions, and 46 (30%) had 5-9 conditions. Risk factors for increasing number of chronic conditions included young age at the time of HSCT, female sex, high radiation dose, and history of chronic graft-versus-host disease. The cumulative incidence at 10 years for common late events was as follows (ordered by the median time-of-onset): osteonecrosis 13.8%, chronic renal insufficiency 26.8%, hypothyroidism 45.1%, growth hormone deficiency 31.2%, female hypogonadism 57.4%, osteopenia 47.7%, cataracts 43.4%, pulmonary dysfunction 63.2%, and male hypogonadism 20.3%. Coexistence of multiple late sequelae was common in HSCT survivors. Our findings provide a basis for more effective patient counseling, optimal surveillance, and early intervention.


Hierarchical bilayered hybrid nanostructural arrays of NiCo2O4 micro-urchins and nanowires as a free-standing electrode with high loading for high-performance lithium-ion batteries.
Fabrication of free -standing binary transition metal oxides, especially NiCo2O4, has attracted significant research interests since these metal oxides are promising candidates for free-standing anodes of lithium-ion batteries (LIBs). However, there remain some problems, especially low loading, for the existing NiCo2O4 anodes. To address the abovementioned issue, it will be a quite feasible solution to combine the advantages of both hierarchical micro/nano-structures and free-standing electrodes to fabricate a free-standing hierarchical micro/nano-structural NiCo2O4 electrode. Herein, we proposed an effective method to controllably synthesize hierarchical bilayered hybrid nanostructural arrays of NiCo2O4(HNAs) micro-urchins and nanowires, denoted as NiCo2O4 HNAs/NF, based on Ni foam (NF) with a high loading via a simple surfactant-assisted hydrothermal and subsequent annealing treatment. In this synthesis, NF was applied as a Ni source for NiCo2O4 without the addition of other Ni-containing reagents, and the pH value played an important role in the synthesis of NiCo2O4 HNAs/NF. Furthermore, the reasonable reaction mechanism of NiCo2O4 HNAs/NF has been discussed in detail and proposed. The as-synthesized NiCo2O4 HNAs/NF possess unique structural advantages such as a large surface area, hierarchical porous structures, and robust connection of NFs and NiCo2O4 active materials. Thus, these unique NiCo2O4 HNAs/NF display excellent electrochemical performance such as a large reversible capacity of 1094 mA h g-1 at a current density of 500 mA g-1 and a good rate capability of 875 mA h g-1 at a large 1000 mA g-1. Especially, a high loading (7 mg cm-2) of NiCo2O4 HNAs/NF, which is much higher than those of other NiCo2O4 electrodes, is beneficial towards the achievement of lightweight and miniaturized LIBs.


A plea for minimally biased naturalistic philosophy.
Naturalistic philosophers rely on literature search and review in a number of ways and for different purposes. Yet this article shows how processes of literature search and review are likely to be affected by widespread and systematic biases. A solution to this problem is offered here. Whilst the tradition of systematic reviews of literature from scientific disciplines has been neglected in philosophy, systematic reviews are important tools that minimize bias in literature search and review and allow for greater reproducibility and transparency. If naturalistic philosophers wish to reduce bias in their research, they should then supplement their traditional tools for literature search and review by including systematic methodologies.


Pathways to neurodegeneration: mechanistic insights from GWAS in Alzheimer's disease, Parkinson's disease, and related disorders.
The discovery of causative genetic mutations in affected family members has historically dominated our understanding of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS). Nevertheless, most cases of neurodegenerative disease are not explained by Mendelian inheritance of known genetic variants, but instead are thought to have a complex etiology with numerous genetic and environmental factors contributing to susceptibility. Although unbiased genome-wide association studies (GWAS) have identified novel associations to neurodegenerative diseases, most of these hits explain only modest fractions of disease heritability. In addition, despite the substantial overlap of clinical and pathologic features among major neurodegenerative diseases, surprisingly few GWAS-implicated variants appear to exhibit cross-disease association. These realities suggest limitations of the focus on individual genetic variants and create challenges for the development of diagnostic and therapeutic strategies, which traditionally target an isolated molecule or mechanistic step. Recently, GWAS of complex diseases and traits have focused less on individual susceptibility variants and instead have emphasized the biological pathways and networks revealed by genetic associations. This new paradigm draws on the hypothesis that fundamental disease processes may be influenced on a personalized basis by a combination of variants - some common and others rare, some protective and others deleterious - in key genes and pathways. Here, we review and synthesize the major pathways implicated in neurodegeneration, focusing on GWAS from the most prevalent neurodegenerative disorders, AD and PD. Using literature mining, we also discover a novel regulatory network that is enriched with AD- and PD-associated genes and centered on the SP1 and AP-1 (Jun/Fos) transcription factors. Overall, this pathway- and network-driven model highlights several potential shared mechanisms in AD and PD that will inform future studies of these and other neurodegenerative disorders. These insights also suggest that biomarker and treatment strategies may require simultaneous targeting of multiple components, including some specific to disease stage, in order to assess and modulate neurodegeneration. Pathways and networks will provide ideal vehicles for integrating relevant findings from GWAS and other modalities to enhance clinical translation.


Large-scale instability in a sheared nonhelical turbulence: Formation of vortical structures.
We study a large-scale instability in a sheared nonhelical turbulence that causes generation of large-scale vorticity. Three types of the background large-scale flows are considered, i.e., the Couette and Poiseuille flows in a small-scale homogeneous turbulence, and the "log-linear" velocity shear in an inhomogeneous turbulence. It is known that laminar plane Couette flow and antisymmetric mode of laminar plane Poiseuille flow are stable with respect to small perturbations for any Reynolds numbers. We demonstrate that in a small-scale turbulence under certain conditions the large-scale Couette and Poiseuille flows are unstable due to the large-scale instability. This instability causes formation of large-scale vortical structures stretched along the mean sheared velocity. The growth rate of the large-scale instability for the "log-linear" velocity shear is much larger than that for the Couette and Poiseuille background flows. We have found a turbulent analogue of the Tollmien-Schlichting waves in a small-scale sheared turbulence. A mechanism of excitation of turbulent Tollmien-Schlichting waves is associated with a combined effect of the turbulent Reynolds stress-induced generation of perturbations of the mean vorticity and the background sheared motions. These waves can be excited even in a plane Couette flow imposed on a small-scale turbulence when perturbations of mean velocity depend on three spatial coordinates. The energy of these waves is supplied by the small-scale sheared turbulence.


[The effect of cefazolin loaded bone matrix gelatin on repairing large segmental bone defects and preventing infection after operation].
To explore the possibility of repair long segmental bone defects and preventing infection with cefazolin loaded bone matrix gelatin (C-BMG). C-BMG was made from putting cefazolin into BMG by vacuum adsorption and freeze-drying techniques. The sustaining period of effective drug concentration in vitro and in vivo was detected by inhabition bacteria, and the drug concentration in local tissues (bone and muscle) and plasma after implantation of C-BMG was examined by high performance liquid chromatography(HPLC). The effective inhibition time to staphylococcus aureus of C-BMG was 22 days in vitro, while 14 days in vivo. The drug concentration in local tissues(bone and muscle) were higher than that of plasma, and the drug concentration in local tissues was higher in early stage, later it kept stable low drug release. It suggested that C-BMG had excellent ability to repair segmental long bone defects. C-BMG can gradually release cefazolin with effective drug concentration and has excellent ability to repair segmental long bone defects. It may be a novel method to repair segmental long bone defects and prevent infection after the operation.


Chemoprevention of skin melanoma: facts and myths.
Melanoma is the most dangerous type of skin cancer. Despite the rise of public awareness, the incidence rate among the white population has been rising constantly for several decades. Systematic improvement in knowledge about the biology of pigment cells and molecular mechanisms of their neoplastic transformation has enhanced the possibility of melanoma chemoprevention. Hence, chemopreventive agents that prevent, inhibit, or reverse melanoma development are being investigated intensively. Among synthetic compounds, especially well studied are lipid-lowering drugs and cyclooxygenase inhibitors. Substances found in everyday diet, such as genistein, apigenin, quercetin, resveratrol, and curcumin may also have potential chemopreventive qualities. However, studies examining the chemopreventive activity of these compounds have shown widely varying results. Early reports on the possible chemopreventive activity of statins and fibrates were not proved by the results of randomized clinical trials. Similarly, case-control studies examining the influence of NSAIDs on the risk of melanoma do not confirm the antitumor activity of cyclooxygenase inhibitors. Further clinical trials involving carefully selected target populations as well as the identification of specific biomarkers of prognostic and predictive value seem to be essential for the evaluation of the chemopreventive activity of the studied substances.


Lipid modulation of calcium flux through CaV2.3 regulates acrosome exocytosis and fertilization.
Membrane lipid regulation of cell function is poorly understood. In early development, sterol efflux and the ganglioside GM1 regulate sperm acrosome exocytosis (AE) and fertilization competence through unknown mechanisms. Here, we show that sterol efflux and focal enrichment of GM1 trigger Ca(2+) influx necessary for AE through CaV2.3, whose activity has been highly controversial in sperm. Sperm lacking CaV2.3's pore-forming α1E subunit showed altered Ca(2+) responses, reduced AE, and a strong subfertility phenotype. Surprisingly, AE depended on spatiotemporal information encoded by flux through CaV2.3, not merely the presence/amplitude of Ca(2+) waves. Using studies in both sperm and voltage clamp of Xenopus oocytes, we define a molecular mechanism for GM1/CaV2.3 regulatory interaction, requiring GM1's lipid and sugar components and CaV2.3's α1E and α2δ subunits. Our results provide a mechanistic understanding of membrane lipid regulation of Ca(2+) flux and therefore Ca(2+)-dependent cellular and developmental processes such as exocytosis and fertilization.


[Neurophysiological manifestations of the monotony state in the human-operators with different alpha-activity hemispheric asymmetry].
This paper presents the monotony state investigation of the human-operator while simulator driving by using a combination of psychophysiological testing, registration of an electrocardiogram and electroencephalogram (EEG). The appearance of specific EEG-pattern (power ascension of the theta-, alpha- and beta-rhythms) during operator activity due to the monotony state progression was revealed. We found out the reduction in health, decrease activity, the increase of the situational anxiety, and the reaction time after 90 minutes of the monotonous activity. The signs of drowsiness were detected at the rest with closed eyes after operator activity. Moreover, these negative manifestations of the monotony state were observed mainly in subjects with domination of the alpha-activity in the left hemisphere.


Optimization and validation of liquid-liquid extraction with low temperature partitioning for determination of carbamates in water.
Using a 2(3) experimental design, liquid-liquid extraction with low temperature partitioning (LLE-LTP) was optimized and validated for analysis of three carbamates (aldicarb, carbofuran and carbaryl) in water samples. In this method, 2.0 mL of sample is placed in contact with 4.0 mL of acetonitrile. After agitation, the sample is placed in a freezer for 3 h for phase separation. The organic extract is analyzed by high performance liquid chromatography with ultraviolet detection (HPLC-UV). For validation of the technique, the following figures of merit were evaluated: accuracy, precision, detection and quantification limits, linearity, sensibility and selectivity. Extraction recovery percentages of the carbamates aldicarb, carbofuran and carbaryl were 90%, 95% and 96%, respectively. Even though extremely low volumes of sample and solvent were used, the extraction method was selective and the detection and quantification limits were between 5.0 and 10.0 microg L(-1), and 17.0 and 33.0 microg L(-1), respectively.


NSUN2-mediated mRNA m5C Modification Regulates the Progression of Hepatocellular Carcinoma.
RNA modification affects many biological processes and physiological diseases. The 5-methylcytosine (m5C) modification regulates the progression of multiple tumors. However, its characteristics and functions in hepatocellular carcinoma (HCC) remain largely unknown. Here, we found that HCC tissues had a higher m5C methylation level than the adjacent normal tissues. Transcriptome analysis revealed that a major function of the hypermethylated genes participated in the phosphokinase signaling pathways, such as the Ras and PI3K-Akt pathways. The m5C methyltransferase NSUN2 was highly expressed in HCC tissues. Interestingly, the expression of many genes was positively correlated with the expression of NSUN2, including GRB2, RNF115, AATF, ADAM15, RTN3, and HDGF. Real-time PCR assays further revealed that the expression of the mRNAs of GRB2, RNF115, and AATF decreased significantly with the down-regulation of NSUN2 in HCC cells. Furthermore, NSUN2 could regulate the cellular sensitivity of HCC cells to sorafenib via modulating the Ras signaling pathway. Moreover, knocking down NSUN2 caused cell cycle arrest. Taken together, our study demonstrates the vital role of NSUN2 in the progression of HCC.


Adult-Onset Still's Disease Associated with Thyroid Dysfunction: Case Report and Review of the Literature.
To our knowledge, the possible unveiled interaction between adult-onset Still's disease (AOSD) with autoimmune thyroid disease (AITD) has never been reported although it is well established that systemic autoimmune disease may usually occur in relation to AITD. As increasingly clear links of AITD with other autoimmune disease such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and primary Sjögren's syndrome (pSS) have been reported, and the incidence of AOSD concurrent AITD draws our attention rapidly. In this study, we searched relevant literatures published in the past 30 years to explore that condition.


Biomarker discovery and biotherapeutics applications of photosynthetic light-harvesting and bioluminescence light-emitting chromophore-protein complexes in stem cell biology and regenerative medicine.
We have since the 1970's embarked on the development of biologically derived fluorophore-protein complexes that will find applications in the communicable and non-communicable disease etiology processes and their cures. We have since then become largely successful in these endeavors along with interspersed contributions also from investigators who have generally restricted to working in confined disciplines. Their encompassment with our works as this investigator has traversed his definitely chosen and not merely a circumstantial, coincidental, or accidental step-wise multi-disciplinary scientific path from biophysics to regenerative medicine spanning these lines of investigations for last four decades have finally yielded the much necessitated disease related applied biological interventions for human benefits. Taking a cue from our early investigations and findings on which we call attention to the identification and characterization of the use of the primary light-emitting lumazine precursor of riboflavin which is 6,7-dimethyl-8-ribityl lumazine-protein complex which we had derived from the bioluminescence bacterium (Photobacterium phosphoreum) wherein it functions as a naturally occurring fluorescence light emitter (LumP). These in vivo phenomena have been a precursor to the subsequent developments in vitro. This in vivo to in vitro investigation path of ours has been also comprised among others of binding of photosynthetic light-harvesting marine dinoflagellate algae (Glenodinium sp.) derived peridinin-chlorophyll a-protein (PerCP) complex-labeled monoclonal antibodies useful in the development of flow cytometry. These fluorescence labeled antibodies bound antigens which include those of communicable infectious diseases (HIV/AIDS - env-gp160, gag-p24), non-communicable but also potential hereditary and malignant disorders (Cancer/Tumor Markers - Melan-A/Mart-1 of melanoma), normal immune response cells (Human/Mouse/species cellular MHC/TCR/CD45/CD33/CD56/CD19/CD41), and of types of stem cells (CD34/CD38/c-Mpl/Oct4/Neuropilin-1/SOX17). Such antigens have been analyzed by us and other investigators by fluorescence-activated cell sorting (FACS - cell surface and intracellular binding), confocal fluorescence microscopy, or/and immunohistochemistry, to determine qualitative and quantitative antigen expression levels and their mechanistic implications. We have followed stem cell differentiation patterns and signaling mechanisms through marker antigen-antibody binding wherein the antibodies are labeled with covalently linked fluorophore-protein complexes or fluorescence emitting chromophores. These complexes among others also have included PerCP. We are also now in the process of developing flow cytometry applications of additional visible light emitting chromophore-protein complexes through industrial collaborations. The United States Navy has long been known for interest in the estimation of changes in illumination intensity in and under the oceans to track movements of enemy ships and other naval vessels.


The Pavlik harness: results in patients over three months of age.
The role of the Pavlik harness in the treatment of congenital dislocation of the hip in 122 patients over 3 months of age is presented. There were 21 patients with hip dislocation and 101 patients with hip dysplasia, with an average age of 5 months. In patients with dysplasia, concentric reduction in the harness was obtained initially, while it took 1 to 4 weeks to achieve reduction in the dislocated hips. The overall success rate was 97%, with no incidence of avascular necrosis. In three patients, the harness did not succeed in reducing the hips, and alternative methods were used with uneventful course. At follow-up, which averaged 5 years, clinical and radiographic examinations were normal in every patient.


Efficient Approach towards Detection and Identification of Copy Move and Image Splicing Forgeries Using Mask R-CNN with MobileNet V1.
With the technological advancements of the modern era, the easy availability of image editing tools has dramatically minimized the costs, expense, and expertise needed to exploit and perpetuate persuasive visual tampering. With the aid of reputable online platforms such as Facebook, Twitter, and Instagram, manipulated images are distributed worldwide. Users of online platforms may be unaware of the existence and spread of forged images. Such images have a significant impact on society and have the potential to mislead decision-making processes in areas like health care, sports, crime investigation, and so on. In addition, altered images can be used to propagate misleading information which interferes with democratic processes (e.g., elections and government legislation) and crisis situations (e.g., pandemics and natural disasters). Therefore, there is a pressing need for effective methods for the detection and identification of forgeries. Various techniques are currently employed for the identification and detection of these forgeries. Traditional techniques depend on handcrafted or shallow-learning features. In traditional techniques, selecting features from images can be a challenging task, as the researcher has to decide which features are important and which are not. Also, if the number of features to be extracted is quite large, feature extraction using these techniques can become time-consuming and tedious. Deep learning networks have recently shown remarkable performance in extracting complicated statistical characteristics from large input size data, and these techniques efficiently learn underlying hierarchical representations. However, the deep learning networks for handling these forgeries are expensive in terms of the high number of parameters, storage, and computational cost. This research work presents Mask R-CNN with MobileNet, a lightweight model, to detect and identify copy move and image splicing forgeries. We have performed a comparative analysis of the proposed work with ResNet-101 on seven different standard datasets. Our lightweight model outperforms on COVERAGE and MICCF2000 datasets for copy move and on COLUMBIA dataset for image splicing. This research work also provides a forged percentage score for a region in an image.


[Contralateral orbital metastasis of a malignant choroid melanoma].
Nine years after enucleation of the right eye because of a choroidal melanoma a choroidal melanoma a metastasis of the melanoma developed in the left orbit. Histologically, the two tumors were identical spindle-cell B melanomas. No other primary tumors or metastases were found. This is only the third case of this rare form of metastasization ever reported.


The influence of warming and biotic interactions on the potential for range expansion of native and nonnative species.
Plant species ranges are expected to shift in response to climate change, however, it is unclear how species interactions will affect range shifts. Because of the potential for enemy release of invasive nonnative plant species from species-specific soil pathogens, invasive plants may be able to shift ranges more readily than native plant species. Additionally, changing climatic conditions may alter soil microbial functioning, affecting plant-microbe interactions. We evaluated the effects of site, plant-soil microbe interactions, altered climate, and their interactions on the growth and germination of three congeneric shrub species, two native to southern and central Florida (Eugenia foetida and E. axillaris), and one nonnative invasive from south America (E. uniflora). We measured germination and biomass for these plant species in growth chambers grown under live and sterile soils from two sites within their current range, and one site in their expected range, simulating current (2010) and predicted future (2050) spring growing season temperatures in the new range. Soil microbes (microscopic bacteria, fungi, viruses and other organisms) had a net negative effect on the invasive plant, E. uniflora, across all sites and temperature treatments. This negative response to soil microbes suggests that E. uniflora's invasive success and potential for range expansion are due to other contributing factors, e.g. higher germination and growth relative to native Eugenia. The effect of soil microbes on the native species depended on the geographic provenance of the microbes, and this may influence range expansion of these native species.


Identification of acetate- or methanol-assimilating bacteria under nitrate-reducing conditions by stable-isotope probing.
Stable-isotope probing (SIP) was used to identify acetate- or methanol-assimilating bacteria under nitrate-reducing conditions in activated sludge. A sludge sample obtained from wastewater treatment systems was incubated in a denitrifying batch reactor fed with synthetic wastewater containing [(13)C]acetate or [(13)C]methanol as the main carbon source and nitrate as the electron acceptor. We analyzed how growth of bacterial populations was stimulated by acetate or methanol as the external carbon source in nitrogen-removal systems. Most of the acetate- or methanol-assimilating bacteria identified by SIP have been known as denitrifiers in wastewater treatment systems. When acetate was used as the carbon source, 16S rRNA gene sequences retrieved from (13)C-labeled DNA were closely related to the 16S rRNA genes of Comamonadaceae (e.g., Comamonas and Acidovorax) and Rhodocyclaceae (e.g., Thauera and Dechloromonas) of the Betaproteobacteria, and Rhodobacteraceae (e.g., Paracoccus and Rhodobacter) of the Alphaproteobacteria. When methanol was used as the carbon source, 16S rRNA gene sequences retrieved from (13)C-DNA were affiliated with Methylophilaceae (e.g., Methylophilus, Methylobacillus, and Aminomonas) and Hyphomicrobiaceae. Rarefaction curves for clones retrieved from (13)C-DNA showed that the diversity levels for methanol-assimilating bacteria were considerably lower than those for acetate-assimilating bacteria. Furthermore, we characterized nitrite reductase genes (nirS and nirK) as functional marker genes for denitrifier communities in acetate- or methanol-assimilating populations and detected the nirS or nirK sequence related to that of some known pure cultures, such as Alcaligenes, Hyphomicrobium, and Thauera. However, most of the nirS or nirK sequences retrieved from (13)C-DNA were clustered in some unidentified groups. On the basis of 16S rRNA gene clone libraries retrieved from (13)C-DNA, these unidentified nir sequences might be identified by examining the nir gene in candidates for true denitrifiers (e.g., the families Comamonadaceae, Hyphomicrobiaceae, Methylophilaceae, and Rhodobacteraceae).


Modeling expression quantitative trait loci in data combining ethnic populations.
Combining data from different ethnic populations in a study can increase efficacy of methods designed to identify expression quantitative trait loci (eQTL) compared to analyzing each population independently. In such studies, however, the genetic diversity of minor allele frequencies among populations has rarely been taken into account. Due to the fact that allele frequency diversity and population-level expression differences are present in populations, a consensus regarding the optimal statistical approach for analysis of eQTL in data combining different populations remains inconclusive. In this report, we explored the applicability of a constrained two-way model to identify eQTL for combined ethnic data that might contain genetic diversity among ethnic populations. In addition, gene expression differences resulted from ethnic allele frequency diversity between populations were directly estimated and analyzed by the constrained two-way model. Through simulation, we investigated effects of genetic diversity on eQTL identification by examining gene expression data pooled from normal quantile transformation of each population. Using the constrained two-way model to reanalyze data from Caucasians and Asian individuals available from HapMap, a large number of eQTL were identified with similar genetic effects on the gene expression levels in these two populations. Furthermore, 19 single nucleotide polymorphisms with inter-population differences with respect to both genotype frequency and gene expression levels directed by genotypes were identified and reflected a clear distinction between Caucasians and Asian individuals. This study illustrates the influence of minor allele frequencies on common eQTL identification using either separate or combined population data. Our findings are important for future eQTL studies in which different datasets are combined to increase the power of eQTL identification.


Molecular bacterial community analysis of clean rooms where spacecraft are assembled.
Molecular bacterial community composition was characterized from three geographically distinct spacecraft-associated clean rooms to determine whether such populations are influenced by the surrounding environment or the maintenance of the clean rooms. Samples were collected from facilities at the Jet Propulsion Laboratory (JPL), Kennedy Space Flight Center (KSC), and Johnson Space Center (JSC). Nine clone libraries representing different surfaces within the spacecraft facilities and three libraries from the surrounding air were created. Despite the highly desiccated, nutrient-bare conditions within these clean rooms, a broad diversity of bacteria was detected, covering all the main bacterial phyla. Furthermore, the bacterial communities were significantly different from each other, revealing only a small subset of microorganisms common to all locations (e.g. Sphingomonas, Staphylococcus). Samples from JSC assembly room surfaces showed the greatest diversity of bacteria, particularly within the Alpha- and Gammaproteobacteria and Actinobacteria. The bacterial community structure of KSC assembly surfaces revealed a high presence of proteobacterial groups, whereas the surface samples collected from the JPL assembly facility showed a predominance of Firmicutes. Our study presents the first extended molecular survey and comparison of NASA spacecraft assembly facilities, and provides new insights into the bacterial diversity of clean room environments .


Hair color measurement and variation.
Pigmentation of hair in humans has been investigated by medical scientists, anthropologists and, more recently, by forensic scientists. In every investigation, hair color must first be defined by the researchers. Subjective color assessment inhibits the reproducibility of experiments and the direct comparison of results. The aim of this study was to objectively measure human hair color and examine the variation found in a population with European ancestry, using the CIE L*a*b* color space. Observer-perceived hair colors were compared with self-reported hair colors and the color as measured by reflective spectrophotometry of 132 subjects of European ancestry. The presented data show that self-reported hair colors and observer-reported colors are similar; however, these categories are not necessarily the best way to categorize hair color for quantitative research. Using a two-step cluster analysis, hair color can be divided into categories or clusters based on spectrophotometric measurements in the CIE L*a*b* color space and these clusters can be well discriminated from each other. This separation is primarily based on the b* (yellow) color component and the clusters show agreement to observer-reported colors. This study illustrates the possibilities for and necessity of objectively defining the hair color phenotype for various downstream applications.


Adverse events following Quadrivalent HPV vaccination reported in Sao Paulo State, Brazil, in the first three years after introducing the vaccine for routine immunization (March 2014 to December 2016).
In March 2014, the Quadrivalent human papilloma virus vaccine (4vHPV) was introduced in the female adolescents vaccination schedule of the National Immunization Program (PNI). A school-based vaccination program was implemented. We conducted a retrospective, descriptive study of the adverse events that took place after HPV vaccination, reported to the Adverse Events Following Immunization (AEFI) Information System in Sao Paulo State, from March 2014 to December 2016. All reports that fit the definitions of the 2014 National Manual on AEFI surveillance were included. AEFI risk was estimated by dividing the number of reports by the number of vaccine doses administered in the period. In the three-year period, 3,390,376 HPV vaccine doses were administered and 465 AEFI reports were registered, with 1,378 signs and symptoms. The reporting rate was 13.72 per 100,000 vaccine doses administered. The reports peaked in the first year of the program. The most frequent AEFI was syncope, with 5.7 reports per 100,000 doses administered, followed by dizziness, malaise, headache and nausea. Overall, 39 AEFI cases (8.4%) were classified as severe , with a reporting rate of 1.15 per 100,000 vaccine doses administered. Most cases were classified as severe because of hospitalization. Among them, there were cases of Guillain-Barré Syndrome, deep vein thrombosis, seizures and miscarriage. All young women recovered without sequelae. We identified five clusters of AEFI reports in four cities; the larger AEFI cluster occurred in the city of Bertioga, in September 2014, involving 13 female adolescents. Our data are in accordance with those from other countries and corroborate the safety of HPV vaccines.


Immunohistochemical staining for Ki-67 and p53 helps distinguish endometrial Arias-Stella reaction from high-grade carcinoma, including clear cell carcinoma.
The distinction of the Arias-Stella reaction from clear cell carcinoma of the endometrium is usually straightforward; however, this differential diagnosis can be difficult when the Arias-Stella reaction occurs outside the setting of pregnancy or in older patients. The differential diagnosis also is problematic when serous or clear cell carcinoma focally arises within an endometrial polyp, as part of "endometrial intra-epithelial carcinoma" (EIC), or in younger patients. The goal of this study was to determine whether immunohistochemical staining can distinguish the Arias-Stella reaction from endometrial high-grade carcinoma, particularly clear cell carcinoma. Cases of endometrial Arias-Stella reaction (n = 27), clear cell carcinoma (n = 11), serous carcinoma (n = 7), and EIC (n = 4) were assessed by immunohistochemical staining with antibodies for Ki-67, p53, estrogen receptor (ER), and progesterone receptor (PR). Composite immunohistochemical scores based on the percentage and intensity of stained cells were calculated, as was the overall positivity (percentage positive cases), using a cutoff value of >/=5% stained cells and at least weak intensity. Appropriate statistical tests were performed. Ki-67 and p53 immunostaining was significantly less in Arias-Stella reaction than in clear cell carcinoma (p < 0.0001 for both) or serous carcinoma/EIC (p < 0.0001 for both), measured by the composite immunohistochemical scores or overall positivity. ER showed a significant difference only between Arias-Stella reaction and clear cell carcinoma; PR showed a significant difference only between Arias-Stella reaction and serous carcinoma/EIC. When clinical or histologic features cannot facilitate the differential diagnosis, immunohistochemical staining for Ki-67 and p53 may help distinguish endometrial Arias-Stella reaction from clear cell carcinoma and other types of high-grade carcinoma.


Serotonergic system antagonists target breast tumor initiating cells and synergize with chemotherapy to shrink human breast tumor xenografts.
Breast tumors comprise an infrequent tumor cell population, termed breast tumor initiating cells (BTIC), which sustain tumor growth, seed metastases and resist cytotoxic therapies. Hence therapies are needed to target BTIC to provide more durable breast cancer remissions than are currently achieved. We previously reported that serotonergic system antagonists abrogated the activity of mouse BTIC resident in the mammary tumors of a HER2-overexpressing model of breast cancer. Here we report that antagonists of serotonin (5-hydroxytryptamine; 5-HT) biosynthesis and activity, including US Federal Food and Drug Administration (FDA)-approved antidepressants, targeted BTIC resident in numerous breast tumor cell lines regardless of their clinical or molecular subtype. Notably, inhibitors of tryptophan hydroxylase 1 (TPH1), required for 5-HT biosynthesis in select non-neuronal cells, the serotonin reuptake transporter (SERT) and several 5-HT receptors compromised BTIC activity as assessed by functional sphere-forming assays. Consistent with these findings, human breast tumor cells express TPH1, 5-HT and SERT independent of their molecular or clinical subtype. Exposure of breast tumor cells ex vivo to sertraline (Zoloft), a selective serotonin reuptake inhibitor (SSRI), reduced BTIC frequency as determined by transplanting drug-treated tumor cells into immune-compromised mice. Moreover, another SSRI (vilazodone; Viibryd) synergized with chemotherapy to shrink breast tumor xenografts in immune-compromised mice by inhibiting tumor cell proliferation and inducing their apoptosis. Collectively our data suggest that antidepressants in combination with cytotoxic anticancer therapies may be an appropriate treatment regimen for testing in clinical trials.


[Analysis of irregular antibodies in the department of transfusion medicine 1984-1988].
In the University Hospital of Hamburg we performed approximate 80,000 screening tests for irregular RBC antibodies in the years 1984-1988. Among 1,815 (2.27%) positive tests, Rhesus and concomitant antibodies occurred in 0.77% (615/80,000), other clinically important antibodies in 0.37% (293 cases). We found significantly less Rh antibodies than in the previous period of the mid seventies (Rh prophylaxis, completely Rh-compatible transfusions).


Sept7b is required for the subcellular organization of cardiomyocytes and cardiac function in zebrafish.
Myofibrils made up of actin, myosin, and associated proteins generate the contractile force in muscle, and, consequently, mutations in these proteins may lead to heart failure. Septins are a conserved family of small GTPases that associate with actin filaments, microtubules, and cellular membranes. Despite the importance of septins in cytoskeleton organization, their role in cardiomyocyte organization and function is poorly characterized. Here, we show that septin 7 is expressed in both embryonic and adult zebrafish hearts and elucidate the physiological significance of sept7b, the zebrafish ortholog of human septin 7, in the heart in embryonic and larval zebrafish. Knockdown of sept7b reduced F-actin and α-cardiac actin expression in the heart and caused disorganization of actin filaments. Electron microscopy of sept7b-depleted larvae showed disorganization of heart myofibrils and partial detachment from Z-disks. Functional studies revealed that knockdown of sept7b leads to reduced ventricular dimensions, contractility, and cardiac output. Furthermore, we found that depletion of sept7b diminished the expression of retinaldehyde dehydrogenase 2, which catalyzes the synthesis of retinoic acid necessary for heart morphogenesis. We further observed that the sept7b and retinoic acid signaling pathways converge to regulate cardiac function. Together, these results specify an essential role for sept7b in the contractile function of the heart.NEW & NOTEWORTHY Knockdown of the zebrafish ortholog of human septin 7 (sept7b) destabilizes cardiac actin and reduces ventricular dimensions, contractility, and cardiac output in larval zebrafish, indicating that sept7b is essential for cardiac function. We further found that sept7b and retinoic acid signaling pathways converge to regulate cardiac function. These data prompt further studies defining the role of sept7b in cardiomyopathies.


Evaluation of the photosynthetic activity in transgenic tobacco plants with altered endogenous cytokinin content: lessons from cytokinin.
Cytokinin is known to be involved in many processes related to plastid development and function but the exact role of cytokinin in photosynthesis remains elusive. To investigate more profoundly the effects of cytokinin in this process, the photosynthetic activity of transgenic Pssuipt and 35S:CKX1 tobacco (Nicotiana tabacum) plants with respectively elevated and reduced endogenous cytokinin content was evaluated. Pigment analysis indicated that elevated endogenous cytokinin content resulted in increased pigment content. Functional analysis of the photosynthetic apparatus by chlorophyll a fluorescence and in vitro electron transport measurements clearly showed that changing the endogenous cytokinin content affects the activity of the photosynthetic apparatus. Surprisingly, both an increase as well as a decrease in cytokinin content results in a better photosynthetic performance. Quenching analysis revealed that the initial responses of the photosynthetic apparatus on a dark-light transition are not affected by changed cytokinin content. However, it has an effect on the further kinetic behavior. Taken together, we suggest that cytokinins can induce structural changes in the different parts of the electron transport chain as also demonstrated by the in vitro electron transport measurements.


Gray matter correlates of behavioral severity in progressive supranuclear palsy.
Behavioral changes occur in progressive supranuclear palsy. This study aimed to identify the anatomic correlate of behavioral severity in progressive supranuclear palsy. We performed standardized tests of behavioral severity (Frontal Behavioral Inventory), cognitive severity (Mini-Mental State Examination), motor severity (Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale Part III), and a 3.0-T volumetric head magnetic resonance imaging scan in 18 prospectively recruited subjects meeting National Institute of Neurological Diseases and Stroke-Society of Progressive Supranuclear Palsy criteria for probable progressive supranuclear palsy. Atlas-based parcellation was utilized to obtain regional gray matter volumes of frontal, temporal, and parietal lobe, and caudate and putamen, and voxel-based morphometry was used to assess voxel-level gray matter loss. We performed correlation analyses between total Frontal Behavioral Inventory score and gray matter volume, as well as assessed gray matter volume across three groups defined according to behavioral severity (mild, moderate, and severe) based on total Frontal Behavioral Inventory score. Specific behaviors, with the exception of apathy that occurred in 83% of the subjects, were relatively infrequent. There was no association between Frontal Behavioral Inventory and cognitive or motor severity. Regions of the frontal lobe, particularly, the lateral posterior frontal cortex, significantly correlated with the total Frontal Behavioral Inventory score when using both regional volume and voxel-level analyses. The groupwise analyses also supported these findings. The presence of apathy correlated with atrophy of the putamen. Behavioral severity in progressive supranuclear palsy appears to be associated with volume loss of frontostriatal regions, in particular, lateral posterior frontal lobe and putamen.


Flow cytometric monitoring of cellular anthracycline accumulation in murine leukemic cells.
Cellular accumulation of daunorubicin (DNR), N-trifluoroacetyl-adriamycin-14-valerate, and THP-Adriamycin (THP-ADR) in doxorubicin sensitive and resistant murine leukemic P388 cells was studied with laser excited flow cytometry. Appearance of DNR fluorescence in P388/S cells was rapid in contrast to that of P388/R cells. A comparison of P388/S and P388/R cells incubated for 20-30 min showed that DNR fluorescence in P388/R cells was one-sixth that of P388/S cells. In contrast, the difference between fluorescence value of P388/S and P388/R cells similarly incubated with N-trifluoroacetyl-adriamycin-14-valerate or THP-ADR was less than 2-fold. Chlorpromazine, verapamil, and trifluoperazine increased the cellular accumulation and cytotoxicity of DNR and THP-ADR but had no major effect on N-trifluoroacetyl-adriamycin-14-valerate fluorescence or cytotoxicity in P388/R cells. Fluorometric and soft agar assays confirmed the data on the effect of these modulators on drug accumulation obtained by the more rapid method of laser flow cytometry.


Place of birth and perinatal mortality.
Analyses of the published results of national surveys and specific studies, as well as of the official stillbirth statistics, consistently point to the conclusion that perinatal mortality is significantly higher in consultant obstetric hospitals than in general practitioner maternity units or at home, even after allowance has been made for the greater proportion of births in hospital at high pre-delivery risk. Unpubliched results of the British births 1970 survey, which have now become available, make possible a direct and authoritative analysis of data on the safest place of birth. Not only does this make the earlier conclusion more certain, but it confounds the doctrine that obstetric intranatal care is particularly beneficial for high pre-delivery risk births. There is no evidence from recent years that the findings of 1970 are not equally valid in the 1980s.


External auditory canal cholesteatoma: clinical and imaging spectrum.
Cholesteatoma is an inflammatory lesion of the temporal bone that uncommonly involves the external auditory canal (EAC). In this large case series, we aimed to define its imaging features and to determine the characteristics most important to its clinical management. Thirteen cases of EAC cholesteatoma (EACC) were retrospectively reviewed. Clinical data were reviewed for the history, presentation, and physical examination findings. High-resolution temporal bone CT scans were examined for a soft-tissue mass in the EAC, erosion of adjacent bone, and bone fragments in the mass. The middle ear cavity, mastoid, facial nerve canal, and tegmen tympani were evaluated for involvement. Patients presented with otorrhea, otalgia, or hearing loss. Eight cases were spontaneous, and five were postsurgical or post-traumatic. CT imaging in all 13 cases showed a soft-tissue mass with adjacent bone erosion. Intramural bone fragments were identified in seven cases. This mass most often arose inferiorly (n = 8) or posteriorly (n = 8), but it was circumferential in two cases. We noted middle ear extension (n = 5), mastoid involvement (n = 4), facial canal erosion (n = 2), and tegmen tympani dehiscence (n = 1). Temporal bone CT shows EACC as a soft-tissue mass within the EAC, with adjacent bone erosion. Bone fragments may be present within the mass. The cholesteatoma may extend into the mastoid or middle ear, or it may involve the facial nerve canal or tegmen tympani. Recognition of this entity and its possible extension is important because it may influence clinical management.


Modified Mesoporous Silica Nanoparticles with a Dual Synergetic Antibacterial Effect.
Application of mesoporous silica nanoparticles (MSNs) as antifouling/antibacterial carriers is limited and specifically with a dual synergetic effect. In the present work, MSNs modified with quaternary ammonium salts (QASs) and loaded with the biocide Parmetol S15 were synthesized as functional fillers for antifouling/antibacterial coatings. From the family of the MSNs, MCM-48 was selected as a carrier because of its cubic pore structure, high surface area, and high specific pore volume. The QASs used for the surface modification of MCM-48 were dimethyloctadecyl[3-(trimethoxysilyl)propyl]ammonium chloride and dimethyltetradecyl[3-(triethoxysilyl)propyl]ammonium chloride. The QAS-modified MCM-48 reveals strong covalent bonds between the QAS and the surface of the nanoparticles. The surface functionalization was confirmed by Fourier transform infrared spectroscopy, thermogravimetric analysis, elemental analysis, and ζ-potential measurements. Additional loading of the QAS-modified MCM-48 with a commercially available biocide (Parmetol S15) resulted in a synergetic dual antibacterial/antifouling effect. Either loaded or unloaded QAS-modified MSNs exhibited high antibacterial performance confirming their dual activity. The QAS-modified MCM-48 loaded with the biocide Parmetol S15 killed all exposed bacteria after 3 h of incubation and presented 100% reduction at the antibacterial tests against Gram-negative and Gram-positive bacteria. Furthermore, the QAS-modified MCM-48 without Parmetol S15 presented 77-89% reduction against the exposed Gram-negative bacteria and 78-94% reduction against the exposed Gram-positive bacteria. In addition, the modified MCM-48 was mixed with coating formulations, and its antifouling performance was assessed in a field test trial in northern Red Sea. All synthesized paints presented significant antifouling properties after 5 months of exposure in real seawater conditions, and the dual antifouling effect of the nanoparticles was confirmed.


Disparate Entry of Adenoviruses Dictates Differential Innate Immune Responses on the Ocular Surface.
Human adenovirus infection of the ocular surface is associated with severe keratoconjunctivitis and the formation of subepithelial corneal infiltrates, which may persist and impair vision for months to years following infection. Long term pathology persists well beyond the resolution of viral replication, indicating that the prolonged immune response is not virus-mediated. However, it is not clear how these responses are sustained or even initiated following infection. This review discusses recent work from our laboratory and others which demonstrates different entry pathways specific to both adenovirus and cell type. These findings suggest that adenoviruses may stimulate specific pattern recognition receptors in an entry/trafficking-dependent manner, leading to distinct immune responses dependent on the virus/cell type combination. Additional work is needed to understand the specific connections between adenoviral entry and the stimulation of innate immune responses by the various cell types present on the ocular surface.


Effect of resistance exercise volume and complexity on EMG, strength, and regional body composition.
This study was designed to examine the effects of a 12-week resistance training program using single versus multiple sets of a complex versus simple exercise on EMG, strength and regional body composition. Twenty-eight untrained men ( n=15) and women ( n=13) performed resistance training twice per week. Group 1 (S-1, n=9) performed one set of a leg press (LP) and bicep curl (BC) exercise, group 2 (M-6, n=9) performed six sets of a LP and BC exercise, and group 3 (C, n=10) was the control group. One-repetition maximums (1RMs) and EMG were measured in the LP and BC during pre-, mid-, and post-training. Lean body mass of the legs and arms were measured pre- and post-training by dual energy X-ray absorptiometry. Results of the study indicated that both S-1 and M-6 groups significantly increased percentage strength pre- to post-training in both the LP and BC [S-1 pre-/post-LP=41.2 (23.7)%, BC=8.5 (6.71)%; M-6 pre-/post-LP=52.6 (12.6)%, BC=22.8 (15.6)%; mean (SD)]. However, compared to S-1, M-6 showed a significantly greater increase in percentage strength in the BC ( P<or=0.05) from pre- to post-testing. Results also showed that M-6 produced a significant increase in biceps (single-joint) muscle EMG values pre- to mid-testing compared to S-1. There were no significant differences found in lean muscle mass gains for the legs or arms in either training group. The data from this study suggest that multiple sets produce a greater increase in percentage strength gain for a simple exercise. It is possible that some type of neural mechanism is responsible for the observed difference.


Gene transfer of endothelial nitric oxide synthase partially restores nitric oxide synthesis and erectile function in streptozotocin diabetic rats.
We determined whether adenoviral gene transfer of endothelial nitric oxide synthase (eNOS) to the penis of streptozotocin induced diabetic rats could improve the impaired erectile response. Two experimental groups of animals were transfected with adenoviruses, including streptozotocin (Sigma Chemical Company, St. Louis, Missouri) diabetic rats with AdCMVbetagal and streptozotocin diabetic rats with AdCMVeNOS. At 1 to 2 days after transfection these study animals underwent cavernous nerve stimulation to assess erectile function and their responses were compared with those of age matched control rats. In control and transfected streptozotocin diabetic rats eNOS and neuronal NOS (nNOS) were examined by Western blot analysis. Constitutive and inducible NOS activities were evaluated in the presence and absence of calcium by L-arginine to L-citrulline conversion and nitrate plus nitrite levels were measured. In control and streptozotocin diabetic penes beta-galactosidase activity and localization were determined. After transfection with AdCMVbetagal beta-galactosidase was localized to the endothelium and smooth muscle cells of the streptozotocin diabetic rat penis. Streptozotocin diabetic rats had a significant decrease in erectile function, as determined by peak and total intracavernous pressure (area under the curve) after cavernous nerve stimulation compared with control rats. Streptozotocin diabetic rats transfected with AdCMVeNOS had peak intracavernous pressure and area under the curve similar to those in control animals. This change in erectile function was a result of eNOS over expression with an increase in eNOS protein expression and constitutive NOS activity as well as an increase in nitric oxide biosynthesis, as reflected by an increase in cavernous nitrate plus nitrite formation. There was no change in nNOS protein expression or calcium independent conversion of NOS (inducible NOS activity). Adenoviral gene transfer of eNOS significantly increased peak and total intracavernous pressure to cavernous nerve stimulation in streptozotocin diabetic rats to a value similar to the response observed in control rats. Our results suggest that eNOS contributes significantly to the physiology of penile erection. These data demonstrate that in vivo adenoviral gene transfer of eNOS can physiologically improve erectile function in the streptozotocin diabetic rat.


Recombinant MPT83 derived from Mycobacterium tuberculosis induces cytokine production and upregulates the function of mouse macrophages through TLR2.
TLR2 recognizes components of Mycobacterium tuberculosis and initiates APC activities that influence both innate and adaptive immunity. M. tuberculosis lipoproteins are an important class of TLR2 ligands. In this study, we focused on recombinant MPT83 (rMPT83) to determine its effects on mouse macrophages. We demonstrated that rMPT83 induced the production of TNF-α, IL-6, and IL-12 p40 and that cytokine induction depended on activated MAPKs, because we observed the rapid phosphorylation of ERK1/2, p38, and JNK in macrophages. Additionally, neutralizing Abs against TLR2 significantly inhibited cytokine secretion and reduced or attenuated the rMPT83-induced activation of p38 and JNK in RAW264.7 cells, a mouse macrophage cell line. Furthermore, rMPT83-induced cytokine production was significantly lower in macrophages from TLR2(-/-) mice than in macrophages from wild-type mice. We further found that prolonged exposure (>24 h) of RAW264.7 cells or macrophages from wild-type and TLR2(-/-) mice to rMPT83 resulted in a significant enhancement of IFN-γ-induced MHC class II expression and an enhanced ability of macrophages to present the rMPT83 peptide to CD4(+) T cells. These results indicated that rMPT83 is a TLR2 agonist that induces the production of cytokines by macrophages and upregulates macrophage function.


Chloroplastic ATP synthase builds up a proton motive force preventing production of reactive oxygen species in photosystem I.
Over-reduction of the photosynthetic electron transport (PET) chain should be avoided, because the accumulation of reducing electron carriers produces reactive oxygen species (ROS) within photosystem I (PSI) in thylakoid membranes and causes oxidative damage to chloroplasts. To prevent production of ROS in thylakoid membranes the H+ gradient (ΔpH) needs to be built up across the thylakoid membranes to suppress the over-reduction state of the PET chain. In this study, we aimed to identify the critical component that stimulates ΔpH formation under illumination in higher plants. To do this, we screened ethyl methane sulfonate (EMS)-treated Arabidopsis thaliana, in which the formation of ΔpH is impaired and the PET chain caused over-reduction under illumination. Subsequently, we isolated an allelic mutant that carries a missense mutation in the γ-subunit of chloroplastic CF0 CF1 -ATP synthase, named hope2. We found that hope2 suppressed the formation of ΔpH during photosynthesis because of the high H+ efflux activity from the lumenal to stromal side of the thylakoid membranes via CF0 CF1 -ATP synthase. Furthermore, PSI was in a more reduced state in hope2 than in wild-type (WT) plants, and hope2 was more vulnerable to PSI photoinhibition than WT under illumination. These results suggested that chloroplastic CF0 CF1 -ATP synthase adjusts the redox state of the PET chain, especially for PSI, by modulating H+ efflux activity across the thylakoid membranes. Our findings suggest the importance of the buildup of ΔpH depending on CF0 CF1 -ATP synthase to adjust the redox state of the reaction center chlorophyll P700 in PSI and to suppress the production of ROS in PSI during photosynthesis.


The prognostic impact of hexaminolevulinate-based bladder tumor resection in patients with primary non-muscle invasive bladder cancer treated with radical cystectomy.
To investigate whether hexaminolevulinate-based (HAL) bladder tumor resection (TURBT) impacts on outcomes of patients with primary non-muscle-invasive bladder cancer (NMIBC) who were eventually treated with radical cystectomy (RC). A total of 131 consecutive patients exhibiting NMIBC at primary diagnosis were retrospectively investigated whether they had undergone any HAL-guided TURBT prior to RC. Uni- and multivariable analyses were used to evaluate the impact of HAL-TURBT on cancer-specific (CSS) and overall survival (OS). The median follow-up was 38 months (IQR 13-56). Of the 131 patients, 69 (52.7%) were managed with HAL- and 62 (47.3%) with white light (WL)-TURBT only prior to RC. HAL-TURBT was associated with a higher number of TURBTs prior to RC (p = 0.002) and administration of intravesical chemotherapy (p = 0.043). A trend towards a higher rate of tumor-associated immune cell infiltrates in RC specimens (p = 0.07) and a lower utilization rate of post-operative systemic chemotherapy (p = 0.10) was noted for patients who were treated with HAL-TURBT. The 5-year CSS/OS was 90.9%/74.5% for the HAL-group and 73.8%/55.8% for the WL-group (p = 0.042/0.038). In multivariable analysis, lymph node tumor involvement (p = 0.007), positive surgical margins (p = 0.001) and performance of WL-TURBT only (p = 0.040) were independent predictors for cancer-specific death. The present data suggest that the resection of NMIBC under HAL exerts a beneficial impact on outcomes of patients who will need to undergo RC during their course of disease. This finding may be due to improved risk stratification as the resection under HAL may allow more patients to be treated timely and adequately.


Treatment of solitary bone cysts by diaphysectomy and bone grafting.
Total diaphysectomy and grafting for solitary bone cysts would appear to produce considerably less recurrence than is found after simple curettage of the lesion and grafting. Three patients with solitary bone cysts, one a primary lesion of the upper humerus and two recurrent lesions involving the intertrochanteric regions, were successfully treated by radical excision of the cyst-bearing region and bone grafting. The operative technique is described as well as the measures taken to prevent discrepancy in limb length or angular deformity ensuing in lesions involving weight-bearing bones such as the femur.


A reappraisal of the terverticillate penicillia using biochemical, physiological and morphological features. I. Numerical taxonomy.
Three-hundred-and-forty-eight strains representing the major species of terverticillate penicillia, and including representatives of other closely and distantly related species, were included in a numerical taxonomic study. One-hundred characters were derived from morphological features, physiological and biochemical activities and SEM micrographs. Strains were compared by both Gower's coefficient and Pattern difference, and clustered using the average linkage algorithm. Thirty-seven species or species-complex clusters were recovered at approximately 70% similarity; they generally corresponded to existing taxonomic concepts. Several species were shown to contain variants or chemotypes which were often supported by differences in conidial shape and ornamentation. The use of different types of characters enabled a number of new and previously accepted species to be shown to be either variants or deteriorated examples of other species. Variation in properties both between and within species was considered, particularly in relation to strain stability.


Streptavidin-coated TiO2 surfaces are biologically inert: protein adsorption and osteoblast adhesion studies.
Non-fouling TiO2 surfaces are attractive for a wide range of applications such as biosensors and medical devices, where biologically inert surfaces are needed. Typically, this is achieved by controlled surface modifications which prevent protein adsorption. For example, polyethylene glycol (PEG) or PEG-derived polymers have been widely applied to render TiO2 surfaces biologically inert. These surfaces have been further modified in order to achieve specific bio-activation. Therefore, there have been efforts to specifically functionalize TiO2 surfaces with polymers with embedded biotin motives, which can be used to couple streptavidin for further functionalization. As an alternative, here a streptavidin layer was immobilized by self-assembly directly on a biotinylated TiO2 surface, thus forming an anti-adhesive matrix, which can be selectively bio-activated. The anti-adhesive properties of these substrates were analyzed by studying the interaction of the surface coating with fibronectin, lysozym, and osteoblast cells using surface plasmon resonance spectroscopy, atomic force microscopy, and light microscopy. In contrast to non-modified TiO2 surfaces, streptavidin-coated TiO2 surfaces led to a very biologically inert substrate, making this type of surface coating a promising alternative to polymer coatings of TiO2 surfaces.


The role of Holliday junction resolvases in the repair of spontaneous and induced DNA damage.
DNA double-strand breaks (DSBs) and other lesions occur frequently during cell growth and in meiosis. These are often repaired by homologous recombination (HR). HR may result in the formation of DNA structures called Holliday junctions (HJs), which need to be resolved to allow chromosome segregation. Whereas HJs are present in most HR events in meiosis, it has been proposed that in vegetative cells most HR events occur through intermediates lacking HJs. A recent screen in yeast has shown HJ resolution activity for a protein called Yen1, in addition to the previously known Mus81/Mms4 complex. Yeast strains deleted for both YEN1 and MMS4 show a reduction in growth rate, and are very sensitive to DNA-damaging agents. In addition, we investigate the genetic interaction of yen1 and mms4 with mutants defective in different repair pathways. We find that in the absence of Yen1 and Mms4 deletion of RAD1 or RAD52 have no further effect, whereas additional sensitivity is seen if RAD51 is deleted. Finally, we show that yeast cells are unable to carry out meiosis in the absence of both resolvases. Our results show that both Yen1 and Mms4/Mus81 play important (although not identical) roles during vegetative growth and in meiosis.


Your company's history as a leadership tool.
When the history of an organization comes up, it's usually in connection with an anniversary--just part of the "balloons and fireworks" (as one business leader characterized his company's bicentennial celebration, knowing that the investment of time and money would have little staying power). A fast-changing world leaves little time for nostalgia and irrelevant details--or, worse, strategies for winning the last war. But the authors, business historians at the Winthrop Group, assert that leaders with no patience for history are missing a vital truth: A sophisticated understanding of the past is one of the most powerful tools they have for shaping the future. The job of leaders, most would agree, is to inspire collective efforts and devise smart strategies for the future. History can be profitably employed on both fronts. As a leader strives to get people working together productively, communicating the history of the enterprise can instill a sense of identity and purpose and suggest the goals that will resonate. In its most familiar form, as a narrative about the past, history is a rich explanatory tool with which executives can make a case for change and motivate people to overcome challenges. Taken to a higher level, it also serves as a potent problem-solving tool, one that offers pragmatic insights, valid generalizations, and meaningful perspectives--a way to cut through management fads and the noise of the moment to what really matters.


Posterior-only approach for treatment of irreducible traumatic Atlanto-axial dislocation, secondary to type-II odontoid fracture; report of a missed case, its management and review of literature.
Odontoid fracture (OF) is among the most common and challenging cervical spine fractures in regards to the treatment and surgical approach. Atlanto-axial dislocation (AAD) is considered a significant complication after failed non-surgical treatment of OF. Traditionally, it requires anterior odontoidectomy followed by posterior C1-C2 reduction and fusion. In latest studies, Atlanto-axial joint (AAJ) remodeling in a posterior-only approach has got attention. We herein present a 30-year-old man with missed type-II OF, presenting with irreducible anterior AAD and progressive neurological deficit. Old non-united OF with dorsal callous formation, compressing spinal cord, was detected. The patient underwent correction of the deformity and reduction of the fracture utilizing the posterior-only approach. AAJ remodeling, callous release and C1-C2 fusion was performed in standard prone position, under fluoroscopic guide and intraoperative electrophysiological monitoring. The patient had uneventful surgery and postoperative course and was neurologically intact with appropriate alignment in 6-month follow-up. The irreducible AAD following type-II OF could be successfully treated with posterior-only approach (C1-C2 fusion). Type-II OF is considered unstable requiring surgical management. Close follow-up and appropriate patient education is mandatory in non-surgical treatment. Irreducible AAD has been managed with anterior odontoid resection and posterior fusion. Several complications of anterior surgery, makes posterior-only approach a noticeable choice.


The financial burden of cancer: estimates from a study of insured women with breast cancer.
The financial impact of cancer can be large, even among persons with comprehensive health insurance policies. Prior studies have found that women with cancer are especially likely to suffer financial hardship. Although controversial, cancer insurance policies are designed to reduce the financial burden of cancer. In this study, we provide estimates of the costs incurred by a cohort of breast cancer patients who were covered by private, Medicare, or Medicaid health insurance. In all, 156 women were interviewed about cancer-related out-of-pocket costs and their knowledge and use of cancer insurance policies. Out-of-pocket expenditures and lost income costs averaged $1,455 per month and varied widely. The majority of out-of-pocket costs were for co-payments for hospitalizations and physician visits. The financial burden of breast cancer accounted for a mean of 98%, 41%, and 26% of monthly income among female breast cancer patients with annual household income levels of < or = $30,000, $30,001-$60,000, and > $60,000, respectively. Cancer insurance policies provided reimbursement for out-of-pocket expenditures for 3% of the women in our study. Our data indicate that even among women with comprehensive health insurance policies, the financial burden of breast cancer can be substantial. Affordable programs that provide reimbursement for medical and nonmedical costs incurred following a diagnosis of breast cancer should be developed, especially for lower income women.


Effect of bulk freezing straws of bovine spermatozoa in a programmed freezer on post - thaw survival.
Twelve ejaculates were extended both in skimmilk and Tris-yolk, packaged in .5-ml French straws and frozen vertically in bulk (10,000 straws/freeze) in a programmed mechanical freezer (Linde CRFC-3). Cooling rates and post-thaw spermatozoal survival in the upper and lower thirds of straws at the following six chamber positions were compared: corner and middle within-goblet positions at center, intermediate and outer chamber locations. Cooling rates generally were faster in the upper third of straws than in the lower third and at the corner rather than the middle within-goblet positions. For combined postthaw incubation periods of 0, 3 and 6 hr at 37 C, motility (photographic and visual) and acrosomal retention (fixed and unfixed samples) were both higher (P greater than .01) for sperm in each extender in the upper third of straws than in the lower third. Spermatozoal motility and acrosomal retention generally were higher (P greater than .05) in each extender at the center rather than at the outer chamber location. Among within-goblet positions, post-thaw survival of sperm was higher (P greater than .05) at the corner than at the middle positions for Tris-yolk but not skimmilk. For comparison semen was frozen in static N vapor in straws held singly (258-straw load) on horizontal racks. For combined incubation periods, post-thaw survival of sperm did not differ (P less than .05) between bulk and static vapor- systems. There also was no difference when each of the six chamber positions was compared individually with static vapor. In conclusion, 33% more straws of semen can be frozen in a mechanical freezer than previously reported, with post-thaw spermatozoal survival comparable to that of sperm in straws frozen conventionally in static vapor.


Inauhzin and Nutlin3 synergistically activate p53 and suppress tumor growth.
Several proteins have been suggested in promoting tumor formation in numerous human tissues by inactivating the tumor suppressor p53. This has generated interest in the development of small molecules to block these inhibitors of p53 and to regain p53 activity. Recently, we identified a small molecule, Inauhzin, which can inhibit SIRT1 activity and activate p53. SIRT1 is a deacetylase that deacetylates p53 and facilitates Mdm2 mediated p53 destabilization. In this study, we tested if combining Inauhzin with Nutlin-3, an inhibitor of MDM2-p53 binding, might synergistically activate p53 to suppress tumor growth. Indeed, at lower doses, combination of Inauhzin and Nutlin-3 exhibited a synergistic effect on inhibiting cell growth and promoting apoptosis in human colon and lung cancer cell lines in a p53-dependent fashion. Minimal effects were observed with treatment of either compound alone. Using a xenograft tumor model, we also showed a synergistic effect with both compounds. Thus, to fully regain p53 activity, targeting its multiple inhibitory proteins might be a better approach. Our study provides evidence supporting this concept for achieving better therapeutic efficacy in tumors that possess wild type p53.


Mitochondrial response of glioma cells to temozolomide.
Metabolic adaptations are central for carcinogenesis and response to therapy, but little is known about the contribution of mitochondrial dynamics to the response of glioma cells to the standard treatment with temozolomide (TMZ). Glioma cells responded to TMZ with mitochondrial mass increased and the production of round structures of dysfunctional mitochondria. At single-cell level, asymmetric mitosis contributed to the heterogeneity of mitochondrial levels. It affected the fitness of cells in control and treated condition, indicating that the mitochondrial levels are relevant for glioma cell fitness in the presence of TMZ.


Viable maternal-effect mutations that affect the development of the nematode Caenorhabditis elegans.
We carried out a genetic screen for viable maternal-effect mutants to identify genes with a critical function relatively early in development. This type of mutation would not have been identified readily in previous screens for viable mutants and therefore could define previously unidentified genes. We screened 30,000 genomes and identified 41 mutations falling into 24 complementation groups. We genetically mapped these 24 loci; only two of them appear to correspond to previously identified genes. We present a partial phenotypic characterization of the mutants and a quantitative analysis of the degree to which they can be maternally or zygotically rescued.


Eurycoma longifolia: Medicinal Plant in the Prevention and Treatment of Male Osteoporosis due to Androgen Deficiency.
Osteoporosis in elderly men is now becoming an alarming health issue due to its relation with a higher mortality rate compared to osteoporosis in women. Androgen deficiency (hypogonadism) is one of the major factors of male osteoporosis and it can be treated with testosterone replacement therapy (TRT). However, one medicinal plant, Eurycoma longifolia Jack (EL), can be used as an alternative treatment to prevent and treat male osteoporosis without causing the side effects associated with TRT. EL exerts proandrogenic effects that enhance testosterone level, as well as stimulate osteoblast proliferation and osteoclast apoptosis. This will maintain bone remodelling activity and reduce bone loss. Phytochemical components of EL may also prevent osteoporosis via its antioxidative property. Hence, EL has the potential as a complementary treatment for male osteoporosis.


Brachial artery reconstruction using the heparin-bonded Sundt shunt.
Fracture stabilization is often desirable prior to vascular repair in the management of major extremity injuries. This principle is particularly important when long vein grafts are required to minimize the risk of anastomotic disruption during the orthopedic portion of the procedure. However, in situations associated with prolonged periods of preoperative ischemia, early reperfusion of the injured extremity would be optimal. This report illustrates two cases of brachial artery injury in which heparin-bonded shunts were used to establish blood flow to the distal extremity before fracture fixation. The shunts were interposed between disrupted arterial segments and reestablished distal perfusion while associated fractures were internally stabilized. Thus, early revascularization allowed the orthopedic repair to proceed in an unhurried fashion. After adequate stabilization of the fracture, arterial reconstruction was completed using saphenous vein interposition grafts. This technique potentially could improve extremity salvage rates and facilitate the repair of arterial injuries associated with unstable long bone fractures.


Quantitative office perimetry.
This study presents a preliminary comparison of six commercially-available automated threshold static parameters, consisting of three projection perimeters (Humphrey Field Analyzer, Squid, and Octopus 500) and three light-emitting diode (LED) perimeters (Dicon 2000, Fieldmaster 50, and Digilab 350). Eighteen individuals were included in the study: 6 normal observers (31-58 years old), six patients with glaucomatous field loss in both eyes (55-70 years old), and six patients with neuro-ophthalmologic or retinal visual field abnormalities in both eyes (12-61 years old). Three aspects of quantitative testing were evaluated: (1) the patients' and normal observers' acceptance and subjective impressions of the test procedure; (2) the technician's ease of operating the device and related tasks; and (3) practitioner-oriented considerations such as test-retest reliability, comparability of test results and testing time. Our results showed that no device was clearly superior to the others in all respects. Patients were most favorably impressed with the Octopus 500, Squid, and the Fieldmaster 50, while technician impressions were most favorable to the Humphrey Field Analyzer and the Squid. The projection perimeters (Humphrey Field Analyzer, Squid, and Octopus 500) were the easiest to perform cross-comparisons of test results, although there was considerable variation in the clarity of data interpretation from one case to another. Test-retest reliability and the time of testing varied among the six automated perimeters.


Model-based design for seizure control by stimulation.
Current brain stimulation paradigms are largely empirical rather than theoretical. An opportunity exists to improve upon their modest effectiveness in closed-loop control strategies with the development of theoretically grounded, model-based designs. Inspired by this need, here we couple experimental data and mathematical modeling with a control-theoretic strategy for seizure termination. We begin by exercising a dynamical systems approach to model seizures (n = 94) recorded using intracranial EEG (iEEG) from 21 patients with medication-resistant, localization-related epilepsy. Although each patient's seizures displayed unique spatial and temporal patterns, their evolution can be parsimoniously characterized by the same model form. Idiosyncracies of the model can inform individualized intervention strategies, specifically in iEEG samples with well-localized seizure onset zones. Temporal fluctuations in the spatial profiles of the oscillatory modes show that seizure onset marks a transition into a regime in which the underlying system supports prolonged rhythmic and focal activity. Based on these observations, we propose a control-theoretic strategy that aims to stabilize ictal activity using static output feedback for linear time-invariant switching systems. Finally, we demonstrate in silico that our proposed strategy allows us to dampen the emerging focal oscillatory sources using only a small set of electrodes. Our integrative study informs the development of modulation and control algorithms for neurostimulation that could improve the effectiveness of implantable, closed-loop anti-epileptic devices.


Cellular pathogenesis of Alzheimer's disease.
The author proposes that paired helical filaments, which contain the protein tau in the fibrillar or beta-pleated sheet conformation, compete with microtubules for binding to nascent, soluble tau. Binding of nascent tau to tau in the beta-pleated sheet conformation autocatalyzes the conformational change into the beta-pleated sheet conformation. As long as sufficient tau is present to stabilize microtubules, neuronal function is normal. However, because paired helical filaments are resistant to proteolysis, they accumulate and eventually bind the bulk of nascent tau. This results in progressive microtubule instability and eventually neuronal death. Senile plaques are involved in Alzheimer's disease pathogenesis in that they contain fibrillar proteins which may function as heteronucleants, catalyzing the fibrillogenesis of other proteins such as tau. In this paradigm, apolipoprotein E4 serves as a heteronucleant for fibrillogenesis of tau.


Practice guideline for forensic pathology. Members of the Forensic Pathology Committee, College of American Pathologists.
The guideline for forensic pathology was prepared by the Forensic Pathology Committee of the College of American Pathologists. The definitional criteria for forensic pathology included in this guideline have been approved both by the House of Delegates and the Board of Governors of the College of American Pathologists. The guideline presents an overview of forensic pathology and an approach to the forensic autopsy and medicolegal death investigation. Emphasis is placed on the role of forensic pathology in maintaining public health, welfare, and safety. The guideline is intended to serve as an educational tool, and its use should be determined by the individual circumstances and settings of specific cases.


Unraveling the underlying mechanism of good electrochemical performance of hard carbon in PC/EC-Based electrolyte.
Although hard carbon in propylene carbonate / ethylene carbonate (PC/EC)-based electrolytes possesses favorable electrochemical characteristics in rechargeable sodium-ion batteries, the underlying mechanism is still vague. Numerous hypotheses have been proposed to solve the puzzle, but none of them have satisfactorily unraveled the reason at the molecular-level. In this study, we firstly attempted to address this mystery through a profound insight into the disparity of the ion solvation/desolvation behavior in electrolyte. Combining the results of density functional theory (DFT) calculations and experiments, the work explains that compared to the sole PC-based electrolyte, Na+-EC4 molecules in the PC/EC-based electrolyte preferentially undergo reduction and contribute to the emergence of a more stable protective film on the surface of hard carbon, leading to the preferable durability and rate capability of the cell. Nevertheless, applying the ion solvation/desolvation model, it also reveals that Na+-(solvent)n molecules in the PC/EC-based electrolyte can achieve faster Na+ desolvation processes than in the PC-based electrolyte alone, contributing to the enhancement of charge transfer kinetics. This research holds great importance in uncovering the possible mechanism of the remarkable electrochemical- properties of hard carbon in PC/EC-based electrolytes, and advancing its practical utilization in future sodium-ion batteries.


Constipation and a low-fiber diet are not associated with diverticulosis.
Asymptomatic diverticulosis is commonly attributed to constipation caused by a low-fiber diet, although evidence for this mechanism is limited. We examined the associations between constipation and low dietary fiber intake with risk of asymptomatic diverticulosis. We performed a cross-sectional study that analyzed data from 539 individuals with diverticulosis and 1569 without (controls). Participants underwent colonoscopy and assessment of diet, physical activity, and bowel habits. Our analysis was limited to participants with no knowledge of their diverticular disease to reduce the risk of biased responses. Constipation was not associated with an increased risk of diverticulosis. Participants with less frequent bowel movements (<7/wk) had reduced odds of diverticulosis compared with those with regular bowel movements (7/wk) (odds ratio [OR], 0.56; 95% confidence interval [CI], 0.40-0.80). Those reporting hard stools also had reduced odds (OR, 0.75; 95% CI, 0.55-1.02). There was no association between diverticulosis and straining (OR, 0.85; 95% CI, 0.59-1.22) or incomplete bowel movement (OR, 0.85; 95% CI, 0.61-1.20). We found no association between dietary fiber intake and diverticulosis (OR, 0.96; 95% CI, 0.71-1.30) in comparing the highest quartile with the lowest (mean intake, 25 vs 8 g/day). In our cross-sectional, colonoscopy-based study, neither constipation nor a low-fiber diet was associated with an increased risk of diverticulosis.


[New trends of medicine manifested at Naeuiwon in the late Chosun period].
Tonifying method has been used to treat various types of deficiency syndrome in traditional Korean medicine. Tonifying medicinal including ginseng and deer horns is one of the various methods of the treatments, but they are recognized as a representative of traditional Korean remedies nowadays in Korea. That is concerned with the new trends of medicine manifested at Naeuiwon (Royal Infirmary) in the late Chosun period. The period that manifested the tonifying method obviously was the reign of King Youngjo (r.1724-1776). King Youngjo who lived longest among Chosun kings considered tonifying yang very important in keeping him healthy. He had taken a large quantity of ginseng, he and others considered the reason for his longevity as taking ginseng. From that time, the method of tonifying yang became one of the principles in health care and treatment as well. In the 19th century, the theory of tonifying method had been changed, in that tonifying yin was considered more important among Naeuiwon physicians. Tonifying yang alone was thought to be harmful because of its warm and dry nature. The main cause of prevalence of tonifying method in Naeuiwon was the fact that it was safe and had little side effects. The method of health care and treatments of the kings was considered as an ideal model by the ordinary people at that time. The new trends of medicine manifested at Naeuiwon in the late Chosun period had a strong influence on traditional Korean medicine, which emphasized the importance of tonifying method.


Nonsurgical management of esophageal adenocarcinoma.
The benefit of induction chemotherapy (IC) before chemoradiotherapy (CRT) for inoperable esophageal adenocarcinoma has not been established. To clarify toxicities and outcomes of combined modality treatment, we performed a retrospective review. Sixty-eight consecutive patients were identified. Fifty-one patients had CRT, 17 had radiotherapy (RT). Fifty-eight received IC before RT. IC consisted of 4 cycles of platinum and fluoropyrimidines followed by CRT 54 Gy with concurrent infusional 5-fluorouracil (5-FU) or capecitabine. Response to IC was assessed at 3 months and response to CRT at 3 months. Time to progression (TTP) and overall survival (OS) are reported. Fifty-four patients were men and 14 were women, with median age 72 years (range, 42-87 years). There were 29 stage II, 33 stage III, 4 stage IVa, and 2 stage IVb tumors. The response 3 months after completion of treatment was 39.6%. No grade 4 toxicity was reported, but 10/58 patients had grade 3 toxicity from IC. The median TTP and OS from RT for the entire cohort was 12 months (95% confidence interval [CI], 7-18) and 16 months (95% CI, 5-27), respectively. The 1- and 2-year survival rates from diagnosis were 73% and 47%, respectively. There was no statistically significant difference in TTP or OS in patients who responded to IC compared with those who did not (median TTP 11 vs. 12 months, respectively; P = .8; median OS 15 vs. 14 months, respectively; P = .8). The outcome in patients with adenocarcinoma of the esophagus after CRT is comparable to unselected surgical series. Response to IC is not always an indicator of eventual outcome.


Cervicofacial actinomycosis.
Cervicofacial actinomycosis is an uncommon, chronic, suppurative, and granulomatous bacterial infection. It is often of dental origin and tends to mimic other dental infections, granulomatous disorders, and cancers. The initial diagnostic workup, predicated upon imaging and tissue biopsies, is frequently nonspecific. A definitive diagnosis is usually rendered only after surgical excision and histologic examination of the cervicofacial mass. We propose a classification of three stages: localized infection without sinus involvement, localized infection with sinus involvement, and disseminated infection, to facilitate recognition, diagnosis, and early aggressive treatment. Untreated infection may be life-threatening. Therapy may require long-term antibiotics; however, many cases may also necessitate complete surgical excision.


Comparison of therapeutic dosimetric data from passively scattered proton and photon craniospinal irradiations for medulloblastoma.
For many decades, the standard of care radiotherapy regimen for medulloblastoma has been photon (megavoltage x-rays) craniospinal irradiation (CSI). The late effects associated with CSI are well-documented in the literature and are in-part attributed to unwanted dose to healthy tissue. Recently, there is growing interest in using proton therapy for CSI in pediatric and adolescent patients to reduce this undesirable dose. Previous comparisons of dose to target and non-target organs from conventional photon CSI and passively scattered proton CSI have been limited to small populations (n ≤ 3) and have not considered the use of age-dependent target volumes in proton CSI. Standard of care treatment plans were developed for both photon and proton CSI for 18 patients. This cohort included both male and female medulloblastoma patients whose ages, heights, and weights spanned a clinically relevant and representative spectrum (age 2-16, BMI 16.4-37.9 kg/m2). Differences in plans were evaluated using Wilcoxon signed rank tests for various dosimetric parameters for the target volumes and normal tissue. Proton CSI improved normal tissue sparing while also providing more homogeneous target coverage than photon CSI for patients across a wide age and BMI spectrum. Of the 24 parameters (V5, V10, V15, and V20 in the esophagus, heart, liver, thyroid, kidneys, and lungs) Wilcoxon signed rank test results indicated 20 were significantly higher for photon CSI compared to proton CSI (p ≤ 0.05) . Specifically, V15 and V20 in all six organs and V5, V10 in the esophagus, heart, liver, and thyroid were significantly higher with photon CSI. Our patient cohort is the largest, to date, in which CSI with proton and photon therapies have been compared. This work adds to the body of literature that proton CSI reduces dose to normal tissue compared to photon CSI for pediatric patients who are at substantial risk for developing radiogenic late effects. Although the present study focused on medulloblastoma, our findings are generally applicable to other tumors that are treated with CSI.


Religion and the Unmaking of Prejudice toward Muslims: Evidence from a Large National Sample.
In the West, anti-Muslim sentiments are widespread. It has been theorized that inter-religious tensions fuel anti-Muslim prejudice, yet previous attempts to isolate sectarian motives have been inconclusive. Factors contributing to ambiguous results are: (1) failures to assess and adjust for multi-level denomination effects; (2) inattention to demographic covariates; (3) inadequate methods for comparing anti-Muslim prejudice relative to other minority group prejudices; and (4) ad hoc theories for the mechanisms that underpin prejudice and tolerance. Here we investigate anti-Muslim prejudice using a large national sample of non-Muslim New Zealanders (N = 13,955) who responded to the 2013 New Zealand Attitudes and Values Study. We address previous shortcomings by: (1) building Bayesian multivariate, multi-level regression models with denominations modeled as random effects; (2) including high-resolution demographic information that adjusts for factors known to influence prejudice; (3) simultaneously evaluating the relative strength of anti-Muslim prejudice by comparing it to anti-Arab prejudice and anti-immigrant prejudice within the same statistical model; and (4) testing predictions derived from the Evolutionary Lag Theory of religious prejudice and tolerance. This theory predicts that in countries such as New Zealand, with historically low levels of conflict, religion will tend to increase tolerance generally, and extend to minority religious groups. Results show that anti-Muslim and anti-Arab sentiments are confounded, widespread, and substantially higher than anti-immigrant sentiments. In support of the theory, the intensity of religious commitments was associated with a general increase in tolerance toward minority groups, including a poorly tolerated religious minority group: Muslims. Results clarify religion's power to enhance tolerance in peaceful societies that are nevertheless afflicted by prejudice.


[The effect of immobilized salivary alkaline phosphatase on remineralization processes].
Relationship between alkaline phosphatase immobilized on apatite and remineralization processes has been studied. The enzyme notably accelerated the remineralization. The course of enzymatic remineralization depended on the source of phosphorus (inorganic phosphorus or beta-glycerophosphate). Calcium incorporation in remineralizing surface was the most rapid in the presence of beta-glycerophosphate. This may be explained by a higher rate of formation of apatite under the effect of immobilized alkaline phosphatase, than of brushite or vitlokite.


Approach to recurrent hepatitis C following liver transplantation.
Hepatitis C-associated liver failure is the most common indication for liver transplantation. Histologic evidence of recurrence is apparent in approximately 50% of hepatitis C virus (HCV)-infected recipients in the first postoperative year. Approximately 10% of HCV-infected recipients will die or lose their allograft due to hepatitis C-associated allograft failure. HCV-infected recipients who undergo retransplantation have 5-year patient and graft survival rates that are broadly similar to those for transplant recipients who are not HCV infected. Although the choice of calcineurin inhibitor, mycophenolate mofetil, or both has not been clearly shown to affect histologic recurrence of hepatitis C, higher cumulative exposure to corticosteroids is associated with increased mortality and more severe histologic recurrence. In contrast to treatment of non-HCV-infected recipients, treatment of HCV-infected transplant recipients for acute cellular rejection is associated with attenuated patient survival. Steroid-resistant rejection with or without the use of T-cell-depleting therapies is associated with a greater than fivefold increased risk of mortality in HCV-infected liver transplant recipients. Pegylated interferon with or without ribavirin should be considered for treatment of recipients with histologically apparent recurrence of hepatitis C before total bilirubin exceeds 3 mg/dL. The role of hepatitis C immunoglobulin and new immunosuppressive agents in the management of hepatitis C after transplant continues to evolve.