Computational model of steroidogenesis in human H295R cells to predict biochemical response to endocrine-active chemicals: model development for metyrapone.
An in vitro steroidogenesis assay using the human adrenocortical carcinoma cell line H295R is being evaluated as a possible screening assay to detect and assess the impact of endocrine-active chemicals (EACs) capable of altering steroid biosynthesis. Data interpretation and their quantitative use in human and ecological risk assessments can be enhanced with mechanistic computational models to help define mechanisms of action and improve understanding of intracellular concentration-response behavior. The goal of this study was to develop a mechanistic computational model of the metabolic network of adrenal steroidogenesis to estimate the synthesis and secretion of adrenal steroids in human H295R cells and their biochemical response to steroidogenesis-disrupting EAC. We developed a deterministic model that describes the biosynthetic pathways for the conversion of cholesterol to adrenal steroids and the kinetics for enzyme inhibition by metryrapone (MET), a model EAC. Using a nonlinear parameter estimation method, the model was fitted to the measurements from an in vitro steroidogenesis assay using H295R cells. Model-predicted steroid concentrations in cells and culture medium corresponded well to the time-course measurements from control and MET-exposed cells. A sensitivity analysis indicated the parameter uncertainties and identified transport and metabolic processes that most influenced the concentrations of primary adrenal steroids, aldosterone and cortisol. Our study demonstrates the feasibility of using a computational model of steroidogenesis to estimate steroid concentrations in vitro. This capability could be useful to help define mechanisms of action for poorly characterized chemicals and mixtures in support of predictive hazard and risk assessments with EACs.


The signal transducer and activator of transcription 1alpha and interferon regulatory factor 1 are not essential for the induction of indoleamine 2,3-dioxygenase by lipopolysaccharide: involvement of p38 mitogen-activated protein kinase and nuclear factor-kappaB pathways, and synergistic effect of several proinflammatory cytokines.
Indoleamine 2,3-dioxygenase (IDO) is induced by interferon (IFN)-gamma-mediated effects of the signal transducer and activator of transcription 1alpha (STAT1alpha) and interferon regulatory factor (IRF)-1. The induction of IDO can also be mediated through an IFN-gamma-independent mechanism, although the mechanism of induction has not been identified. In this study, we explored whether lipopolysaccharide (LPS) or several proinflammatory cytokines can induce IDO via an IFN-gamma-independent mechanism, and whether IDO induction by LPS requires the STAT1alpha and IRF-1 signaling pathways. IDO was induced by LPS or IFN-gamma in peripheral blood mononuclear cells and THP-1 cells, and a synergistic IDO induction occurred when THP-1 cells were cultured in the presence of a combination of tumor necrosis factor-alpha, interleukin-6 or interleukin-1beta. An electrophoretic mobility shift assay using STAT1alpha and IRF-1 consensus oligonucleotide probes showed no STAT1alpha or IRF-1 binding activities in LPS-stimulated THP-1 cells. Further, the LPS-induced IDO activity was inhibited by both p38 mitogen-activated protein kinase (MAPK) and nuclear factor-kappaB (NF-kappaB) inhibitors. These findings suggest that the induction of IDO by LPS in THP-1 cells is not regulated by IFN-gamma via recruitment of STAT1alpha or IRF-1 to the intracellular signaling pathway, and may be related to the activity of the p38 MAPK pathway and NF-kappaB.


Optimization of a culture technique for the isolation of Listeria monocytogenes from faecal samples.
A culture technique employing cold enrichment at 4 degrees C followed by selective enrichment and plating at higher temperatures (30 degrees C) was used to isolate Listeria monocytogenes from faecal samples. The samples were held at 4 degrees C for 15 weeks and cultured weekly to assess the sensitivity of the culture after cold storage for different lengths of time. No media, Listeria selective enrichment broth (LSEB), nutrient broth (NB) and saline were used as cold storage medium. Cold storage increased the frequency of Listeria positive samples. The sensitivity of the culture for Listeria spp. and L. monocytogenes was 72 and 94%, and 56 and 61% after third and seventh week of cold storage, respectively. When the results of third and seventh week of cold storage were combined, the sensitivity was 100% for Listeria spp. and 94% for L. monocytogenes. LSEB and NB as storage medium increased Listeria positive samples after the first week of cold storage but did not maintain the increase thereafter while saline had an adverse effect on the growth of the bacteria. However, samples held in no media in a pilot study involving monthly sampling of a herd revealed better results. Detection limit of the culture media was also investigated. The lowest concentration detected by culture media was 3.17 organisms/ml. This was seven organisms/g for known Listeria positive sample. The faecal samples spiked with 10-fold dilutions of L. monocytogenes and held at 4 degrees C revealed that the sample spiked with 3.17 x 10-1 cfu/ml organisms resulted in growth after the second week of cold storage. The results suggest that the culture technique employing cold enrichment followed by selective enrichment and plating is more sensitive, the storage of faecal samples in no media when compared with the samples in storage medium, LSEB, NB and saline, during cold enrichment is a better application and culture of faeces, immediately after collection, at third and seventh week of cold enrichment produce more satisfactory results.


Chilblain-like lesions with prominent bullae in a patient with COVID-19.
A 27-year-old patient presented with acral chilblain-like lesions atypical of dermatological presentations appearing in current reports of COVID-19. Prominent bullae had formed on the dorsa of her toes and became haemorrhagic 2 days after the initial presentation. The patient had no underlying medical conditions, including any history of collagen vascular disease, Raynaud's phenomenon, chilblains or cold exposure, and was not taking any medications. The patient reported 10 days of ageusia and anosmia 6 weeks prior to the manifestation of her toe lesions, with no other symptoms. A nasopharyngeal swab test for SARS-CoV-2 RNA was positive. It is important that physicians recognise the myriad of cutaneous lesions associated with COVID-19 in this ongoing pandemic.


New criteria for the diagnosis of ankylosing spondylitis.
Criteria for ankylosing spondylitis are useful for two main purposes. First, to provide unity of diagnosis in population surveys; secondly, in the field of therapeutic assessment. This paper is concerned with criteria used largely in the former role, i.e. as an epidemiological tool. Critical formulation and subsequent evaluation of criteria is important if a realistic measure of disease prevalence is to be obtained. The New York criteria have provided the general currency for diagnosis epidemiologically in recent years, but their value, in their originally published form, has been questioned for various reasons. Attempts have been made to improve these criteria or to suggest alternatives. Although increased sophistication of the original New York criteria has doubtless been achieved, the position regarding the diagnosis of ankylosing spondylitis continues to represent a challenge. The main concern is that the present "index of truth" for the disease, radiological sacroiliitis, is all too often a delayed feature, presenting only after pain has been present for some time. A second problem is the difficulty in diagnosing with confidence the early changes of sacroiliac sclerosis and erosion, and the degree of intra- and inter-observer error arising from these changes. Newer techniques such as radioisotope scintigraphy and computerised tomography (CT) are unlikely to replace the traditional pelvic radiograph. The way forward is more likely to be in the direction of how existing data are processed rather than what is used to obtain them. In this vein, suitable mathematical/biological models coupled with computer technology could provide realistic tools through a system of probability weighting of existing criteria.


Differentiation of metallic and dielectric nanoparticles in solution by single-nanoparticle collision events at the nanoelectrode.
In this work, we demonstrate a highly effective method to generate and detect single-nanoparticle (NP) collision events on a nanoelectrode in aqueous solutions. The nanoelectrode of a nanopore-nanoelectrode nanopipette is first employed to accumulate NPs in solution by dielectrophoresis (DEP). Instead of using amperometric methods, the continuous individual NP collision events on the nanoelectrode are sensitively detected by monitoring the open-circuit potential changes of the nanoelectrode. Metallic gold NPs (GNPs) and insulating polystyrene (PS) NPs with various sizes are used as the model NPs. Due to the higher conductivity and polarizability of GNPs, the collision motion of a GNP is different from that of a PS NP. The difference is distinct in the shape of the transient potential change and its first time derivative detected by the nanoelectrode. Therefore, the collision events by metallic and insulating NPs on a nanoelectrode can be differentiated based on their polarizability. DEP induced NP separation and cluster formation can also be probed in detail in the concentrated mixture of PS NPs and GNPs.


Synthesis of Broad Band Violet-Blue Light-Emitting Core-Shell Cr3+:C-CaIn₂O₄ Nanowires.
We developed a simple, effective and green method for synthesis of broad band violet-blue lightemitting core-shell Cr3+:C-CaIn²O⁴ nanowires (1-10 mol% of Cr3+) using aloe vera nectar. Calcium indate (CaIn²O⁴) is an important wideband gap semiconductor that could be explored for optical doping such as transition metals and/or rare-earths useful to make light-emitters, optical data storage, and other devices. The nectar embeds the cations in a gel so as it controls an ionic conversion Cr6+ to Cr3+ in ambient air. When grafting a carbon layer on surface of Cr3+:CaIn²O⁴ crystallites it yields a core-shell structure of tailored dielectric, optical and other properties. Asprepared Cr3+:CaIn²O⁴-C exhibits two bands at 270 nm and 360 nm, which got shifted-to at 265 and 370 nm when annealed at higher dosage of Cr3+ ions. These are the ligand-to-metal O2- to Cr3+ charge transfer bands. We studied the light-emission properties in analyzing migration, transfer and recombination processes of light-induced e--h+ pairs in detail in correlation to a Cr3+:CaIn²O⁴-C core-shell nanostructure.


Malignant fibrous histiocytoma of the heart. A case report.
Malignant fibrous histiocytoma is a recently recognised common sarcoma of late adult life which, rarely, may arise in the heart. Unlike the atrial myxoma, which it may mimic clinically, malignant fibrous histiocytoma is a far more aggressive tumour with a greater tendency for local recurrence and infiltration. A case of a primary intracardiac malignant fibrous histiocytoma is reported and relevant published reports reviewed.


Computer-assisted horizontal translational osseous genioplasty: a simple method to correct chin deviation.
Different genioplasty techniques are applied for the adjustment of chin area deformities such as chin deviation. Thirty patients with simple facial asymmetry due to chin deviation underwent computer-assisted horizontal translational osseous genioplasty. In this technique, a surgical guide was used to cut a bone strip from the side where the chin should be transferred to; then, the same bone strip was used for the filling of the gap that was formed on the opposite side. According to the experience gained from this study, the authors believe that computer-assisted horizontal translational osseous genioplasty is a simple and reliable technique for patients with facial asymmetry due to chin deviation.


[Study on preparation and quantity determination of Scrophularia ningpoensis dispensing granules].
To develop the preparation method and to determine the quantity of effective constituents of Scrophularia ningpoensis dispensing granules. Nine experiments were carried out through L9 (3(4)) orthogonal design. The contents of harpagoside and cinnamic acid were determined by HPLC method. The optimal extraction process was as follows: the slices were soaked in water in the ratio of 1:8 for 0.5 h, then they were decocted for 2 h. For the second time, 6 times of water was added and sustained for 1.5 h. Harpagoside and cinnamic acid were linear within the ranges of 0.0776-1.552 microg (r=0.9999) and 0.01446-0.4339 microg (r=0.9999), respectively. The average recoveries were 100.4% (RSD 1.98%, n=6) and 98.27% (RSD1.35%, n=6), respectively. Ten batches of granules were determined. The extraction process is scientific and the determination method is suitable for quality control of Scrophularia ningpoensis dispensing granules.


Identification of tumor homing peptides by utilizing hybrid feature representation.
Cancer is one of the serious diseases, recent studies reported that tumor homing peptides (THPs) play a key role in treatment of cancer. Due to the experimental methods are time-consuming and expensive, it is urgent to develop automatic computational approaches to identify THPs. Hence, in this study, we proposed a novel machine learning methods to distinguish THPs from non-THPs, in which the peptide sequences firstly encoded by pseudo residue pairwise energy content matrix (PseRECM) and pseudo physicochemical property (PsePC). Moreover, the least absolute shrinkage and selection operator (LAASO) was employed to select optimal features from the extracted features. All of these selected features were fed into support vector machine (SVM) for identifying THPs. We achieved 89.02%, 88.49%, and 94.58% classification accuracy on the Main, Small, and Main90 dataset, respectively. Experimental results showed that our proposed method outperforms the existing predictors on the same benchmark datasets. It indicates that the proposed method may be a useful tool in identifying THPs. The datasets and codes used in current study are available at https://figshare.com/articles/online_resource/iTHPs/16778770.Communicated by Ramaswamy H. Sarma.


Determination of the natural abundance delta15N of nortropane alkaloids by gas chromatography-isotope ratio mass spectrometry of their ethylcarbamate esters.
An important route for the detoxification of tropane alkaloids involves N-demethylation to the nor-compounds followed by further degradation. In order to study the mechanisms of the pertinent reactions, a suitable means to determine the isotope ratios of the substrates and products is required. However, the polarity and functionality of the nortropane compounds makes their analysis as free bases difficult. A method is described which allows both the quantification of nortropane alkaloids and the determination of their natural abundance delta(15)N values. The protocol exploits the derivatisation of the alkaloids by reaction with ethyl chloroformate in aqueous medium and the quantitative extraction of the ensuing ethylcarbamate esters. The improved chromatographic properties of these derivatives gives ample separation of the isomeric nortropine and norpseudotropine for measurement of their delta(15)N (per thousand) values by isotope ratio mass spectrometry interfaced to gas chromatography. Adequate separation could not be achieved with the underivatised compounds. Repeatability and precision are sufficient to allow differences in the delta(15)N values (Deltadelta(15)N) > 0.8 per thousand to be measured, with a standard deviation routinely approximately 0.3 per thousand. The methodology has been tested by determining the changes in the delta(15)N values of nortropine and norpseudotropine during degradation by cell suspension cultures of a Pseudomonas strain expressing a specific capacity for tropine catabolism. The precision and reproducibility are shown sufficient to allow the evolution of the delta(15)N values to be followed during the fermentation.


Copy number variant detection in inbred strains from short read sequence data.
We have developed an algorithm to detect copy number variants (CNVs) in homozygous organisms, such as inbred laboratory strains of mice, from short read sequence data. Our novel approach exploits the fact that inbred mice are homozygous at virtually every position in the genome to detect CNVs using a hidden Markov model (HMM). This HMM uses both the density of sequence reads mapped to the genome, and the rate of apparent heterozygous single nucleotide polymorphisms, to determine genomic copy number. We tested our algorithm on short read sequence data generated from re-sequencing chromosome 17 of the mouse strains A/J and CAST/EiJ with the Illumina platform. In total, we identified 118 copy number variants (43 for A/J and 75 for CAST/EiJ). We investigated the performance of our algorithm through comparison to CNVs previously identified by array-comparative genomic hybridization (array CGH). We performed quantitative-PCR validation on a subset of the calls that differed from the array CGH data sets.


Wireless gyroscope platform enabled by a portable media device for quantifying wobble board therapy.
The wobble board enables a therapy strategy for rehabilitation of the ankle foot complex. Quantification of therapy, such as through the use of a wobble board, can facilitate a therapist's acuity for advancing and optimizing the overall therapy strategy. The portable media device, such as an iPod, can be equipped with a software application to function as a wireless gyroscope platform. Integration of the wobble board with the portable media device functioning as a wireless gyroscope enables the potential for patient to therapist interaction through connectivity to the Internet. A patient can conduct wobble board therapy for the ankle foot complex from the convenient vantage point of a homebound setting with therapy data transmitted wirelessly as email attachments. The gyroscope signal of the wobble board therapy can be consolidated into a feature set for machine learning classification. Using a multilayer perceptron neural network considerable classification accuracy has been achieved for differentiating between a hemiplegic affected ankle and unaffected ankle while using a wobble board. The combination of machine learning, wireless systems, such as a portable media device functioning as a wireless gyroscope, and a conventional therapy device, such as a wobble board, are envisioned to advance the capability to optimally impact the rehabilitation experience.


Safety and Immunological Efficacy of a DNA Vaccine Encoding the Androgen Receptor Ligand-Binding Domain (AR-LBD).
The androgen receptor (AR) is a key oncogenic driver of prostate cancer, and has been the primary focus of prostate cancer treatment for several decades. We have previously demonstrated that the AR is also an immunological target antigen, recognized in patients with prostate cancer, and targetable by means of vaccines in rodent models with delays in prostate tumor growth. The current study was performed to determine the safety and immunological efficacy of a GMP-grade plasmid DNA vaccine encoding the ligand-binding domain (LBD) of the AR, pTVG-AR. Groups of male mice (n = 6-10 per group) were evaluated after four or seven immunizations, using different schedules and inclusion of GM-CSF as a vaccine adjuvant. Animals were assessed for toxicity using gross observations, pathological analysis, and analysis of serum chemistries. Animals were analyzed for evidence of vaccine-augmented immunity by tetramer analysis. Survival studies using different immunization schedules and inclusion of GM-CSF were conducted in an autochthonous genetically engineered mouse model. No significant toxicities were observed in terms of animal weights, histopathology, hematological changes, or changes in serum chemistries, although there was a trend to lower serum glucose in animals treated with the vaccine. There was specifically no evidence of toxicity in other tissues that express AR, including liver, muscle, hematopoietic, and brain. Vaccination was found to elicit AR LBD-specific CD8+ T cells. In a subsequent study of tumor-bearing animals, animals treated with vaccine had prolonged survival compared with control-immunized mice. These studies demonstrate that, in immunocompetent mice expressing the target antigen, immunization with the pTVG-AR vaccine was both safe and effective in eliciting AR-specific cellular immune responses, and prolonged the survival of prostate tumor-bearing mice. These findings support the clinical evaluation of pTVG-AR in patients with recurrent prostate cancer. Prostate 77:812-821, 2017. © 2017 Wiley Periodicals, Inc.


Developmental and FGF-2-mediated regulation of syndecans (1-4) and glypican in oligodendrocytes.
Differentiating cells undergo developmentally regulated changes in cell-cell and cell-matrix adhesion that control migration through microenvironments, proliferation, and differentiation. The diversity of the patterns of expression of heparan sulfate proteoglycans (HSPGs), coupled with their interactions with extracellular matrix, cell adhesion molecules, and growth factors, has emphasized their critical importance in the regulation of these events. Syndecans (1-4), glypican, and cerebroglycan are membrane-associated HSPGs that have been implicated in these events in various tissues and several tumor cell lines. We have examined the developmental expression and FGF-2-mediated regulation of these HSPGs during differentiation within a specific lineage of primary cells, oligodendrocytes (OL). Northern analyses of highly purified, developmentally synchronized populations of OL-lineage cells at three stages of differentiation (early and late progenitors and mature OLs) showed that the expression of individual forms of these syndecans and glypican are developmentally regulated. Specifically, the level of expression of syndecan-2 and -4 and glypican mRNAs increased as the cells differentiated from proliferative late progenitors to postmitotic mature cells. The expression of syndecan-1 and -3 had the inverse developmental pattern. Therefore, these two sets of molecules may have different roles in regulating the onset of terminal differentiation in OLs. The levels of mRNA expression were regulated by FGF-2: in late progenitors, FGF-2 induced a doubling of the mRNA levels of syndecan-2, -3, and -4, while those for syndecan-1 and glypican remained unaffected; in mature OLs, the levels of syndecan-1 mRNA were up-regulated, the levels of syndecan-2 and -4 and glypican were down-regulated. These results suggest that the individual syndecan molecules have distinct functions during the differentiation process and that multiple levels of regulation must exist, leading to a changing repertoire of these molecules during OL lineage progression and myelinogenesis.


Signaling functions of the tyrosine residues in the betac chain of the granulocyte-macrophage colony-stimulating factor receptor.
The granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor (GMR) is a heterodimeric receptor expressed by myeloid lineage cells. Binding of GM-CSF activates at least one receptor-associated tyrosine kinase, JAK2, and rapidly induces tyrosine phosphorylation of the GMR betac-chain (GMRbeta), but not the GMR alpha-chain (GMRalpha). To examine the role of GMRbeta tyrosine phosphorylaiton, each of the 8 tyrosine residues in the cytoplasmic domain of the human GMRbeta was mutated to phenylalanine (GMRbeta-F8), and this mutant receptor was expressed with wild-type GMRalpha in the interleukin-3-dependent murine hematopoietic cell line, Ba/F3. GM-CSF induced tyrosine phosphorylation of multiple cellular proteins in cells expressing GMRbeta-F8 , including JAK2 and STAT5. However, GM-CSF-induced tyrosine phosphorylation of both SHP2 and SHC was reduced or absent compared with wild-type. Next, a series of 8 receptors were generated, each containing only a single, restored, tyrosine residue. Tyrosine 577 was found to be sufficient to regenerate GM-CSF-dependent phosphorylation of SHC, and any of Y577, Y612, or Y695 was sufficient to regenerate GM-CSF-inducible phosphorylation of SHP2. Despite the signaling defect to SHC and SHP2, Ba/F3 cells expressing GMRbeta-F8 were still able to proliferate in response to 10 ng/mL of human GM-CSF, although mitogenesis was impaired compared with wild-type GMRbeta, and this effect was even more prominent at lower concentrations of GM-CSF (1 ng/mL). Overall, these results indicate that GMRbeta tyrosine residues are not necessary for activation of the JAK/STAT pathway or for proliferation, viability, or adhesion signaling in Ba/F3 cells, although tyrosine residues significantly affect the magnitude of the response. However, specific tyrosine residues are needed for activation of SHC and SHP2.


OpenCell: Endogenous tagging for the cartography of human cellular organization.
Elucidating the wiring diagram of the human cell is a central goal of the postgenomic era. We combined genome engineering, confocal live-cell imaging, mass spectrometry, and data science to systematically map the localization and interactions of human proteins. Our approach provides a data-driven description of the molecular and spatial networks that organize the proteome. Unsupervised clustering of these networks delineates functional communities that facilitate biological discovery. We found that remarkably precise functional information can be derived from protein localization patterns, which often contain enough information to identify molecular interactions, and that RNA binding proteins form a specific subgroup defined by unique interaction and localization properties. Paired with a fully interactive website (opencell.czbiohub.org), our work constitutes a resource for the quantitative cartography of human cellular organization.


Altered regulation of brain glucose metabolism as a cause of neurodegenerative disorders?
At present, search for the causes of neurodegenerative diseases represents a major topic in brain research. Acquired disturbances of cell metabolism are supposed to be a cause of the two most important neurodegenerative disorders in ageing, like senile dementia of the Alzheimer type and Parkinson's disease, resulting in measurable decreases of in vivo and post mortem cerebral glucose metabolism. Accumulating evidence indicates that insulin plays an important role in the regulation of brain glucose homeostasis in the central nervous system and has trophic effects on neurons. It has been suggested that the reduction of brain glucose metabolism in neuro-degenerative disorders may be related to a defect of the neuronal insulin-insulin receptor-interaction. It will be the aim of our study to demonstrate whether there exist any changes in the content of insulin, its receptor and/or in the functionality of the insulin receptor and its signal transduction in neurodegenerative disorders as Alzheimer's and Parkinson's disease.


Identification of the GRAS gene family in the Brassica juncea genome provides insight into its role in stem swelling in stem mustard.
GRAS transcription factors are known to play important roles in plant signal transduction and development. A comprehensive study was conducted to explore the GRAS family in the Brassica juncea genome. A total of 88 GRAS genes were identified which were categorized into nine groups according to the phylogenetic analysis. Gene structure analysis showed a high group-specificity, which corroborated the gene grouping results. The chromosome distribution and sequence analysis suggested that gene duplication events are vital for the expansion of GRAS genes in the B. juncea genome. The changes in evolution rates and amino acid properties among groups might be responsible for their functional divergence. Interaction networks and cis-regulatory elements were analyzed including DELLA and eight interaction proteins (including four GID1, two SLY1, and two PIF3 proteins) that are primarily involved in light and hormone signaling. To understand their regulatory role in growth and development, the expression profiles of BjuGRASs and interaction genes were examined based on transcriptome data and qRT-PCR, and selected genes (BjuGRAS3, 5, 7, 8, 10, BjuB006276, BjuB037910, and BjuA021658) had distinct temporal expression patterns during stem swelling, indicating that they possessed diverse regulatory functions during the developmental process. These results contribute to our understanding on the GRAS gene family and provide the basis for further investigations on the evolution and functional characterization of GRAS genes.


Assessment of wound bio-burden and prevalence of multi-drug resistant bacteria during open wound management.
To describe the bacterial bio-burden of open-treated wounds and make comparisons with bite wounds. Retrospective multicentre study. Microbial culture between 2011 and 2013 from open-treated wounds in dogs and cats (initiation of therapy n=88, follow-up n=52) were compared to those from bite wounds (n=184). Bacteria were identified and tested for antibiotic susceptibility by two accredited laboratories. In total, 77/88 (88%) of open-treated wounds yielded positive bacterial cultures at the beginning of treatment, decreasing to 27/52 (52%) during treatment. Upon initial evaluation, 42/88 (48 %) of open-treated wounds were considered infected with multi-drug-resistant bacteria, with a drop to 22/52 (41%) during therapy. Bite wounds yielded fewer positive cultures 88/184 (48%) with only 11/182 (6%) being affected by multi-drug-resistant bacteria. Bacteria found most commonly in open-treated wounds were Enterococcus subspecies, Escherichia coli, Staphylococcus pseudintermedius and Pseudomonas aeruginosa. The bacterial populations of open-treated wounds differed markedly from the bite wounds. The high incidence of multi-drug-resistant strains in open wounds highlights the need for alternatives to antibiotics.


Knowledge and Other Predictors of Child Welfare Clinic Completion among Children Aged 24-59 Months in the Garu-Tempane District of Northern Ghana: A Cross-Sectional Study of Caregivers.
While completion of the Child Welfare Clinic (CWC) schedule for children remains a crucial factor in the prevention of illness and promotion of better child health, there has been low attendance among caregivers in Ghana. This study examined knowledge of 220 caregivers of children aged 24-59 months on CWC and other factors influencing attendance in the Garu-Tempane District of Northern Ghana. This health facility-based descriptive cross-sectional study was carried out among caregivers of children using a structured questionnaire. Descriptive and inferential statistics comprising frequency, percentage, Fisher's exact test, and logistic regression were adopted in analysing the data. Less than half (46.9%) of the children completed their CWC schedules. Meanwhile, caregivers' knowledge on CWC was 97.7%. Children aged 37-48 months (AOR = 0.42, 95%CI = 0.21-0.86, p=0.017) and 49-59 months (AOR = 0.27, 95%CI = 0.10-0.77, p=0.014), respectively, had lower odds of completing CWC. Children with caregivers not having any formal education also had lower odds of completing CWC (AOR = 0.45, 95%CI = 0.21-0.95, p=0.036). Educational programmes on the importance of CWC completion should focus on caregivers with children aged 37 months and above and those caregivers with low educational level. It is further recommended that studies be conducted to explore the extent of association between caregivers' marital status, occupation, level of knowledge, and child CWC completion in the Garu-Tempane District.


Growth factor modulation of steroidogenic acute regulatory protein and luteinization in the pig ovary.
In vivo and in vitro luteinization were investigated in the porcine ovary, with emphasis on expression of steroidogenic acute regulatory protein (StAR). StAR mRNA and protein as well as cytochrome P450 side-chain cleavage mRNA (P450scc) increased during the luteal phase in the corpus luteum (CL) and were absent in regressed CL. Cytochrome P450 aromatase mRNA (P450arom) was not detectable at any time in CL. In vitro luteinization of granulosa cells occurred over 96 h in culture, during which P450arom mRNA was present at 1 h after cell isolation but not detectable at 6 h; and P450scc and StAR mRNAs were first detectable at 6 h and 48 h, respectively. Incubation of cultures with insulin-like growth factor I (IGF-I, 10 ng/ml), dibutyryl cAMP (cAMP, 300 microM), or their combination, induced measurable StAR mRNA at 24 h (p < 0.05), increased progesterone accumulation at 48 h, and elevated both StAR and P450scc expression through 96 h. Incubation of luteinized granulosa cells with epidermal growth factor (EGF, 10 nM) changed their phenotype from epithelioid to fibroblastic, eliminated steady-state StAR expression, and interfered with cAMP induction of StAR mRNA and progesterone accumulation. EGF had little apparent effect on P450scc mRNA abundance. It is concluded that StAR expression characterizes luteinization, and early luteinization is induced by cAMP and IGF-I in vitro. Further, EGF induces a morphological and functional phenotype that appears similar to an earlier stage of granulosa cell function.


Ustur Case 0846: Modeling Americium Biokinetics after Intensive Decorporation Therapy.
Decorporation therapy with salts of diethylenetriamine-pentaacetic acid binds actinides, thereby limiting uptake to organs and enhancing the rate at which actinides are excreted in urine. International Commission on Radiological Protection reference biokinetic models cannot be used to fit this enhanced exertion simultaneously with the baseline actinide excretion rate that is observed prior to the start of therapy and/or after the effects of therapy have ceased. In this study, the Coordinated Network on Radiation Dosimetry approach, which was initially developed for modeling decorporation of plutonium, was applied to model decorporation of americium using data from a former radiation worker who agreed to donate his body to the US Transuranium and Uranium Registries for research. This individual was exposed to airborne Am, resulting in a total-body activity of 66.6 kBq. He was treated with calcium-diethylenetriamine-pentaacetic acid for 7 y. The time and duration of intakes are unknown as no incident reports are available. Modeling of different assumptions showed that an acute intake of 5-μm activity median aerodynamic diameter type M aerosols provides the most reasonable description of the available pretherapeutic data; however, the observed Am activity in the lungs at the time of death was higher than the one predicted for type M material. The Coordinated Network on Radiation Dosimetry approach for decorporation modeling was used to model the in vivo chelation process directly. It was found that the Coordinated Network on Radiation Dosimetry approach, which only considered chelation in blood and extracellular fluids, underestimated the urinary excretion of Am during diethylenetriamine-pentaacetic acid treatment; therefore, the approach was extended to include chelation in the liver. Both urinary excretion and whole-body retention could be described when it was assumed that 25% of chelation occurred in the liver, 75% occurred in the blood and ST0 compartment, and the chelation rate constant was 1 × 10 pmol d. It was observed that enhancement of urinary excretion of Am after injection of diethylenetriamine-pentaacetic acid exponentially decreased to the baseline level with an average half-time of 2.2 ± 0.7 d.


Down syndrome congenital heart disease: a narrowed region and a candidate gene.
Down syndrome (DS) is a major cause of congenital heart disease (CHD) and the most frequent known cause of atrioventricular septal defects (AVSDs). Molecular studies of rare individuals with CHD and partial duplications of chromosome 21 established a candidate region that included D21S55 through the telomere. We now report human molecular and cardiac data that narrow the DS-CHD region, excluding two candidate regions, and propose DSCAM (Down syndrome cell adhesion molecule) as a candidate gene. A panel of 19 individuals with partial trisomy 21 was evaluated using quantitative Southern blot dosage analysis and fluorescence in situ hybridization (FISH) with subsets of 32 BACs spanning the region defined by D21S16 (21q11.2) through the telomere. These BACs span the molecular markers D21S55, ERG, ETS2, MX1/2, collagen XVIII and collagen VI A1/A2. Fourteen individuals are duplicated for the candidate region, of whom eight (57%) have the characteristic spectrum of DS-CHD. Combining the results from these eight individuals suggests the candidate region for DS-CHD is demarcated by D21S3 (defined by ventricular septal defect), through PFKL (defined by tetralogy of Fallot). These data suggest that the presence of three copies of gene(s) from the region is sufficient for the production of subsets of DS-CHD. This region does not include genes located near D21S55, previously proposed as a "DS critical region," or the genes encoding collagens VI and XVIII. Of the potential gene candidates in the narrowed DS-CHD region, DSCAM is notable in that it encodes a cell adhesion molecule, spans more than 840 kb of the candidate region, and is expressed in the heart during cardiac development. Given these properties, we propose DSCAM as a candidate for DS-CHD.


Dual-task processing when task 1 is hard and task 2 is easy: reversed central processing order?
Five psychological refractory period (PRP) experiments were conducted with an especially time-consuming first task (Experiments 1, 3, and 5: mental rotation; Experiments 2 and 4: memory scanning) and with equal emphasis on the first task and on the second (left-right tone judgment). The standard design with varying stimulus onset asynchronies (SOAs) was extended by a condition with blocked SOAs in Experiments 3 and 4. Based on the optimization account (Miller, Ulrich, & Rolke, 2009) it was expected that participants would-at short, but not long SOAs-tend to process the relatively fast central stage of Task 2 before the time-consuming central stage of Task 1 and consequently emit the response to Task 2 before the response to Task 1. Such an optimization tendency was found, more so for the mental rotation task and for the blocked SOA condition. The results indicate that preparation, Task 1 characteristics, and TRT (total reaction time) optimization are-among others-factors influencing central processing order in PRP tasks.


The current state of abortion law and practice in Northern Ireland.
This paper reviews current abortion law and practice in Northern Ireland (NI). It explores the origins of NI's abortion law and its complexity in relation to current practice. It reviews issues relating to women seeking terminations in NI and Great Britain and reviews attempts by the Family Planning Association in NI to require the Department of Health, Social Services and Public Safety NI to clarify the current legal basis for termination of pregnancy and to provide guidance for health professionals engaged in this practice. The paper also discusses some of the issues surrounding abortion in NI and seeks to explain why this subject is causing controversy and debate, especially following a judicial review in February and Marie Stopes opening a termination service in Belfast.


Pain response classification does not predict long-term outcome in patients with low back pain who are sick-listed.
Prospective cohort study nested in a randomized clinical trial. To investigate the prognostic value of pain response classification at initial physiotherapy examination in patients with low back pain (LBP) who are sick-listed. Recurrent and chronic LBP accounts for a substantial proportion of all absence from work. In predicting outcome in patients with LBP, psychosocial factors are thought to play an important role, while findings from clinical examination seem to be of more limited value. Mechanical evaluation, using repeated end range spinal movements that result in specific pain responses, has been shown to be of some value. The study included 351 patients sick-listed because of LBP with or without sciatica. Prior to clinical examination, the patients completed a comprehensive questionnaire including questions on pain, function, and psychosocial factors. The physiotherapy examination included a standardized mechanical evaluation. Patients were classified into 3 groups according to their pain response: centralization, peripheralization, or no response. Outcomes were obtained by national register data, medical records, and a postal questionnaire at 1 year. At 1-year follow-up, 65% of the patients had returned to work. All pain response groups showed significant and clinically important improvements in both pain and disability. No significant differences were found between pain response groups in any outcome measure. Results remained unchanged after adjustment for potential confounders. The prognostic value of pain response classification seems limited in patients sick-listed from work because of LBP.


Epinephrine fails to hasten hemodynamic recovery in fully developed canine anaphylactic shock.
Epinephrine (Epi) is the treatment of choice for reversing cardiovascular collapse in anaphylactic shock (AS). However, there are few data supporting its use in this condition, and most treatment guidelines have been anecdotally derived. In the present study, the time course of hemodynamic recovery from maximal hypotension was investigated in a canine model of AS in which Epi was administered by the intravenous (IV), subcutaneous (SQ) and intramuscular (IM) routes on different occasions. The findings obtained with Epi treatment were compared to those in a nontreatment study. Ragweed-sensitized dogs were examined in respective studies approximately 5 weeks apart in which Epi was administered by one of the above routes in a randomized design. Either Epi (0.01 mg/kg) or placebo was administered at maximal hypotension, and hemodynamics were followed for 3 h after shock. The animals were studied while ventilated and anesthetized. Mean arterial pressure (MAP), cardiac output, stroke volume (SV), pulmonary wedge pressure (Pwp) and plasma Epi concentrations were obtained at each measurement interval. In the IV study, Epi produced a transient immediate increase in MAP, SV and Pwp as compared to the nontreatment study (144 vs. 52 mm Hg; 32 vs. 12 ml; 9 vs. 5 mm Hg; p < 0.01), but no differences were observed 15 min after shock. Hemodynamics were not different between Epi and no treatment at any intervals when Epi was given by the SQ and IM routes. AS compared with the placebo study, plasma Epi concentrations were higher in the IV and IM studies, but not in the SQ study. Although higher Epi concentrations were observed in the IM and IV studies, a sustained benefit in hemodynamic recovery was not observed in this anesthetized, ventilated canine model. In AS, when administered during maximum shock after mediators have already been released, a single IM, IV or SQ dose of Epi may have limited utility in the treatment of cardiovascular collapse. Earlier administration of Epi, before maximal hypotension occurs, may produce a more beneficial effect.


Recent advances in the direct construction of enantioenriched stereocenters through addition of radicals to internal alkenes.
The development of new synthetic methods involving radical intermediates to control the absolute configuration of newly formed stereocenters has seen unprecedented growth in the past few decades. Despite significant advances in this topic, catalytic asymmetric direct construction of stereocenters through addition of radicals to internal alkenes is of special interest due to its potential to simultaneously build (more than) two consecutive stereogenic centers. Methodologies such as chiral Lewis acid catalysis, organocatalysis, and transition metal catalysis have been successfully leveraged to exert enantiocontrol in this challenging domain. This tutorial review highlights the recent significant progress in the realm of rapidly and conveniently building enantioenriched stereocenters via addition of radicals to internal alkenes, with an emphasis on mechanistic scenarios governing the absolute stereochemistry and unmet challenges in this emerging and promising field.


Cytokines plasma levels during antidepressant treatment with sertraline and transcranial direct current stimulation (tDCS): results from a factorial, randomized, controlled trial.
The inflammatory hypothesis of depression states that increased levels of pro-inflammatory cytokines triggered by external and internal stressors are correlated to the acute depressive state. This hypothesis also suggests that pharmacotherapy partly acts in depression through anti-inflammatory effects. Transcranial direct current stimulation (tDCS) is a novel, promising, non-invasive somatic treatment for depression, although its antidepressant mechanisms are only partly understood. We explored the effects of tDCS and sertraline over the immune system during an antidepressant treatment trial. In a 6-week, double-blind, placebo-controlled trial, 73 antidepressant-free patients with unipolar depression were randomized to active/sham tDCS and sertraline/placebo (2 × 2 design). Plasma levels of several cytokines (IL-2, IL-4, IL-6, IL-10, IL-17a, IFN-γ, and TNF-α) were determined to investigate the effects of the interventions and of clinical response on them. All cytokines, except TNF-α, decreased over time, these effects being similar across the different intervention-groups and in responders vs. non-responders. tDCS and sertraline (separately and combined) acute antidepressant effects might not specifically involve normalization of the immune system. In addition, being one of the first placebo-controlled trials measuring cytokines over an antidepressant treatment course, our study showed that the decrease in cytokine levels during the acute depressive episode could involve a placebo effect, highlighting the need of further placebo-controlled trials and observational studies examining cytokine changes during depression treatment and also after remission of the acute depressive episode.


Homograft implantation for aortic valve replacement since 15 years: results and follow-up.
The use of homografts in aortic valve replacement is an alternative to other prostheses and has been established in our department for 15 years. Since 1992, 360 homografts (HG) have been implanted in adult patients (mean age 51.6 years, 72.8% male). Prospective follow-up was done on an annual basis. Thirty-day mortality was 5.0% (n = 17); after 5, 10, and 15 years, survival was 88.3%, 84.6%, and 76.0%, respectively. Out of 39 late deaths, 11 were valve-related (10 HG infections, 1 aortic aneurysm). Freedom from reoperation was 99.4% 1 year after operation; after 5, 10, and 15 years it was 94.1%, 78.2%, and 67.3%, respectively. Indications for HG explantation were graft infections (n = 20), calcification (n = 16), regurgitation > grade II (n = 17), perforation (n = 8), and paravalvular leakage (n = 1). Eleven transitoric ischemic attacks, 2 strokes, and 1 cerebral bleeding event were recorded. In echocardiography, the transvalvular pressure gradient changed from 10.55 to 15.02 (P = .004), 19.9 mmHg (P = .056), and 37 mmHg (not applicable) after 5, 10, and 15 years, respectively. Mean HG regurgitation was grade 0.49 before discharge and increased to 1.0 (P < .001), 0.91, and 2.5 after 5, 10, and 15 years, respectively. Ejection fraction increased from 61.9% to 64% after 5 years and to 66% after 10 years (P = .021) and then decreased to 63.5% after 15 years. Comparing HG with other valve prostheses, survival and graft durability seem to be confirmed. They are vulnerable to infections. The hemodynamic performance is good, and hemorrhagic or thrombo-embolic events are rare.


Neck circumference is associated with non-traditional cardiovascular risk factors in individuals at low-to-moderate cardiovascular risk: cross-sectional analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).
Neck circumference (NC) is associated with traditional cardiovascular risk factors (CVRF), but its usefulness to identify earlier atherogenic risk has been scarcely examined. Associations of NC with non-traditional CVRF were investigated in participants at low-to-moderate risk from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). 807 individuals (35-54 years) without obesity, diabetes or cardiovascular disease was stratified into quartiles of NC (cut-off for men: 36.5; 37.9 and 39.5 cm; women: 31.4; 32.5 and 34 cm) and traditional and non-traditional risk factors (lipoprotein subfractions by Vertical Auto Profile, adiponectin, leptin, E-selectin) were compared across groups. In linear regression models, associations of NC with non-traditional risk factors were tested for the entire sample and for low-risk group (≤ 2 CVRF). In both sexes, BMI, waist circumference, systolic and diastolic blood pressure, fasting and 2-h plasma glucose, HOMA-IR, triglycerides, leptin, E-selectin, small dense LDL-cholesterol, IDL-cholesterol, VLDL3-cholesterol and TG/HDL ratio increased significantly, while HDL2-cholesterol and HDL3-cholesterol decreased across NC quartiles. In linear regression models, a direct association [β(95% CI)] of NC with leptin [(0.155 (0.068-0.242); 0.147 (0.075-0.220)], E-selectin [(0.105 (0.032-0.177); 0.073 (0.006 to 0.140)] and small-dense LDL [(1.866 (0.641-3.091); 2.372 (1.391-3.353)] and an inverse association with HDL2-cholesterol [(- 0.519 (- 0.773 to - 0.266); - 0.815 (- 1.115 to 0.515)] adjusted for age were detected for men and women, respectively. Our findings indicate that measurement of NC may be useful for an earlier identification of unfavorable atherogenic metabolic profile in middle-aged individuals at lower cardiovascular risk level.


[Development of a System to Use Patient's Information Which is Required at the Radiological Department].
The purpose of this study is to develop a new system to get and share some data of a patient which are required for a radiological examination not using an electronic medical chart or a radiological information system (RIS), and also to demonstrate that this system is operated on cloud technology. I used Java Enterprise Edition (Java EE) as a programing language and MySQL as a server software, and I used two laptops as hardware for client computer and server computer. For cloud computing, I hired a server of Google App Engine for Java (GAE). As a result, I could get some data of the patient required at his/her examination instantly using this system. This system also helps to improve the efficiency of examination. For example, it has been useful when I want to decide radiographic condition or to create CT images such as multi-planar reconstruction (MPR) or volume rendering (VR). When it comes to cloud computing, the GAE was used experimentally due to some legal restrictions. From the above points it is clear that this system has played an important role in radiological examinations, but there has been still few things which I have to resolve for cloud computing.


Photoinduced ring opening reactions and subsequent thermal ring closure reactions in the thymine-ammonia system and related systems.
The photo-induced ring opening reactions of thymine (Thy) and 1-methylthymine (MeT) with ammonia and with methylamine (MA) at basic pH, and the subsequent ring closure reactions of the resulting adducts, have been studied. In the photo-induced reaction of Thy with ammonia, the dominant product is the E form of N-carbamoyl-3-amino-2-methylacrylamide (IIIa). Heating or acid treatment of aqueous IIIa results in rapid formation of Thy as final product, while allowing IIIa to stand at 4 degrees C produces Thy and two isomeric Thy hydrates, namely trans- and cis-6-hydroxy-5,6-dihydrothymine (Ia and IIa). The main products in the other reactions have analogous structures and undergo analogous ring closure reactions. Incubation of IIIa (and similar adducts) in phosphate buffer near pH 7 significantly enhances the rate of hydrate formation; other weak acid/conjugate base buffer systems also increase the rate of hydrate formation. A mechanism leading from opened ring adduct (e.g.IIIa) to hydrates (e.g.Ia and IIa) is proposed; ring closure leads initially to a dihydrothymine intermediate containing a 6-amino moiety, while further reaction with water produces the observed hydrates. The results described may be relevant to understanding the fate of cross-links generated by photo-induced reaction of thymine moieties in DNA with lysine residues in nuclear proteins (e.g. histones) when they are formed in a cellular environment. Decomposition of such cross-links, catalyzed by cellular phosphate, could lead to production of thymine hydrates attached to lysine residues contained in the protein partner and concurrent generation of an apyrimidinic site in the DNA partner.


[Clinical application of sentinel lymph node biopsy under the guidance of contrast-enhanced ultrasound plus methylene blue in patients with breast cancer].
To explore the application feasibility of contrast-enhanced ultrasound (CEUS) plus methylene blue in sentinel lymph node biopsy (SLNB) for breast cancer and determine the ultrasonographic features of sentinel lymph node (SLN). The microbubbles of SonoVue were injected subcutaneously and intradermally into tumor side of areola. The images were observed to record the size, number, lymphatic door, aspect ratio, enhanced time and enhanced mode of SLN. Methylene blue was injected into SLN under the guidance of ultrasound. The marked SLNs were dissected for pathological examinations. Based upon the results, the specimens were divided into SLN metastasis and SLN non-metastasis groups. A total of 34 breast cancer patients were recruited. Among them, SLN was detected preoperatively in 31 patients by CEUS and the rate was 91.2%. And the postoperative results showed that 14 were confirmed positive (metastasis group) and 17 negative (non-metastasis group). The sensitivity, specificity, accuracy and false negative rate of CEUS for detecting SLNs were 93.3% (14/15), 100% (16/16), 96.8% (30/31) and 6.7% (1/15) respectively. The model of stepwise regression analysis showed that lymphatic door, aspect ratio and enhanced mode were helpful to differentiate SLN metastasis and SLN non-metastasis groups. SLNB under the guidance of CEUS plus methylene blue offer prompt and accurate localization with a lower cost. It may enhance the detection rate of SLNB in breast cancer.


Determination of fatty acids in human sweat during fasting using GC/MS.
Fatty acids (FAs) are biological molecules that are used as major metabolic fuels, and are concerned in important metabolic processes. We have performed a non-invasive and technically rapid and simple method for collecting sweat from humans, followed by GC/MS determination. The sweat was collected from each volunteer (the middle finger) by spraying 70% ethanol aqueous solution (no harmful solvent) into a 1.5-cm(3) plastic vial. Analysis of FAs in sweat showed that the sweat solution contains lauric acid (C12:0), myristic acid (C14:0), palmitic acid (C16:0), oleic acid (C18:1), and stearic acid (C18:0). Here, it is demonstrated that FA concentrations for 4 young subjects correlated positively with percent of body fat (r = 0.78) and that the total FA levels for them increased progressively with increasing fasting time when a subject fasted throughout the experiment.


Bayesian Modeling of Temporal Coherence in Videos for Entity Discovery and Summarization.
A video is understood by users in terms of entities present in it. Entity Discovery is the task of building appearance model for each entity (e.g., a person), and finding all its occurrences in the video. We represent a video as a sequence of tracklets, each spanning 10-20 frames, and associated with one entity. We pose Entity Discovery as tracklet clustering, and approach it by leveraging Temporal Coherence (TC): the property that temporally neighboring tracklets are likely to be associated with the same entity. Our major contributions are the first Bayesian nonparametric models for TC at tracklet-level. We extend Chinese Restaurant Process (CRP) to TC-CRP, and further to Temporally Coherent Chinese Restaurant Franchise (TC-CRF) to jointly model entities and temporal segments using mixture components and sparse distributions. For discovering persons in TV serial videos without meta-data like scripts, these methods show considerable improvement over state-of-the-art approaches to tracklet clustering in terms of clustering accuracy, cluster purity and entity coverage. The proposed methods can perform online tracklet clustering on streaming videos unlike existing approaches, and can automatically reject false tracklets. Finally we discuss entity-driven video summarization- where temporal segments of the video are selected based on the discovered entities, to create a semantically meaningful summary.


Group-index engineering in silicon corrugated waveguides.
We demonstrate group-index engineering in a one-dimensional periodic silicon structure consisting of a deep-etched laterally corrugated waveguide with circular holes patterned onto its wide section. Our theoretical analysis, supported by experimental results, shows that the first-order optical mode can propagate inside the Brillouin zone with a relatively high group index over a wide frequency range. Nearly constant group index as high as 13.5 over a wavelength range of approximately 14 nm is experimentally demonstrated in a 50-microm-long waveguide.


Prognostic Value of the Stem Cell Markers Epcam and CD133 Expression Of Gallbladder Adenocarcinoma.
To investigate the expressions and prognostic value of stem cell markers, EpCAM and CD133, in benign and malignant lesions of gallbladder. Expression of EpCAM and CD133 was assessed in gallbladder adenocarcinoma (n = 100), peritumoral tissues (n = 46), adenoma (n = 30), polyp (n = 15), and chronic cholecystitis (n = 35) by using immunohistochemistry. The positive rates of EpCAM and CD133 expression were significantly higher in gallbladder adenocarcinoma than that in peritumoral tissues (χ2(EpCAM7) = 15.36, χ2(CD133) =16.05; Ps < 0.01), adenoma (χ2 (EpCAM) =10.92, χ2(CD133) = 11.09; Ps < 0.01), polyp (χ2(EpCAM) = 8.88, χ2(CD133) = 10.43; Ps < 0.01) and chronic cholecystitism (χ2(EpCAM) = 28.58, χ2(CD133) =25.57; Ps < 0.01). In adenocarcinoma, the positive expression of EpCAM and CD133 was significanctly associated with differentiation, tumor mass, lymph node metastasis, invasion and overall survival. Notably, the benign lesions with positive EpCAM or /and CD133 expression showed moderately or severely atypical hyperplasia in gallbladder epithelium. The high consistence was found between the expressive levels of EpCAM and CD133 in gallbladder adenocarcinoma (χ2 = 10.02, P < 0.01). Unitivariate Kaplan-Meier analysis showed that high level of EpCAM (P = 0.004) and CD133 (P = 0.012) were associated with poor overall survival. The elevated expression of EpCAM and/or CD133 is closely related to the carcinogenesis, progression, clinical biological behaviors, and prognosis of gallbladder adenocarcinoma.


Lactobacillus plantarum ZJ316 improves the quality of Stachys sieboldii Miq. pickle by inhibiting harmful bacteria growth, degrading nitrite and promoting the gut microbiota health in vitro.
Microbial contamination and nitrite accumulation are the two major concerns in the quality control of fermented vegetables. In the present study, a lactic acid bacteria strain Lactobacillus plantarum ZJ316 (ZJ316) was inoculated during Stachys sieboldii Miq. (SSM) fermentation, and the effects of ZJ316 on the quality and bacterial community of SSM during fermentation were investigated. It was observed that ZJ316 could avoid the occurrence of the nitrite peak and maintain the nitrite content of fermented SSM at a low level. Gas chromatography-mass spectrometry (GC-MS) results suggested that ZJ316 gave good flavor to the fermented SSM. 16S rDNA sequencing showed that Firmicutes was the dominant flora after ZJ316 inoculation, and the abundance of Proteobacteria decreased at the same time. At the level of the genus, SSM fermented by ZJ316 had a more obvious inhibitory effect on Pseudomonas on the 7th day compared with the naturally fermented SSM. Additionally, the effect of ZJ316-fermented SSM on gut microbiota modulation was also evaluated using an in vitro fecal fermentation system. The results revealed that ZJ316 had a relatively subtle influence on intestinal communities with a potentially positive impact on probiotics such as Lactobacillus and Bifidobacterium and a negative impact on Enterobacteriaceae. Furthermore, SSM fermented by ZJ316 promoted the production of short-chain fatty acids (SCFAs) in the human intestine. These results demonstrate that L. plantarum ZJ316 can be used as a good starter in the fermentation process of pickles.


Digital Marine: An online platform for blended learning in a marine experimental biology module, the Schmid Training Course.
For over 20 years, the Schmid Training Course (STC) has offered unique opportunities for marine biology students from European universities to learn about marine model organisms. While the topics of the course have continuously changed over the years with the advent of new research techniques and discoveries, the pedagogical approach has remained largely the same - a combination of lectures, lab practicals, and field excursions. Several life science researchers, who have taught in the STC for many years, sought to bring the course's pedagogical approach into the 21st century, and with the support of Erasmus+ Programme of the European Community funding, the Digital Marine project was developed. Digital Marine began in 2018 as an international partnership between the six research centers from which the STC instructors hail, and its main objective was to introduce a flipped, blended approach to learning and teaching with respect to established and emerging marine biological model systems. The Digital Marine platform, which covers 12 marine model organisms, is now publicly available.


Neck-rail position in the free stall affects standing behavior and udder and stall cleanliness.
This study tested the effect of neck-rail position on stall usage and udder and stall cleanliness. Thirty Holstein lactating cows were tested in groups of 6. Each group was tested with each of 5 neck-rail positions (130, 145, 160, 175, and 190 cm from the rear curb, at a constant height of 125 cm above the bedded surface) for 1 wk, with the order of testing allocated in a 5 x 5 Latin square. When the neck rail was positioned further from the rear curb, cows spent less time standing with their front 2 hooves in the stall (2.2 +/- 0.26 h/d at 130 cm vs. 1.7 +/- 0.27 h/d at 190 cm, mean +/- SE) and more time standing with all 4 hooves in the stall (0.0 +/- 0.02 h/d at 130 cm vs. 0.6 +/- 0.07 h/d at 190 cm). These effects of neck-rail position tended to be more marked for smaller cows, perhaps because the standing behavior of larger cows was restricted even in the 190-cm treatment. Cows were more likely to defecate and urinate in the stalls when the neck rail was positioned further from the rear curb. Cows using these stalls tended to have dirtier udders and these stalls required more cleaning time (0.4 +/- 0.16 min/d at the 130-cm position vs. 1.6 +/- 0.35 min/d at the 190-cm position). In summary, positioning the neck rail further from the curb increased the time that cows spent standing fully in the stall. This change in standing behavior is likely beneficial for hoof health, but reduced udder and stall cleanliness.


Two G-protein-coupled-receptor candidates, Cand2 and Cand7, are involved in Arabidopsis root growth mediated by the bacterial quorum-sensing signals N-acyl-homoserine lactones.
Many Gram-negative bacteria use N-acyl-homoserine lactones (AHLs) as quorum sensing (QS) signaling molecules to coordinate their group behavior. Recently, it was shown that plants can perceive and respond to these bacterial AHLs. However, little is known about the molecular mechanism underlying the response of plants to bacterial QS signals. In this study, we show that the promotion of root elongation in wild type Arabidopsis thaliana induced by the AHLs N-3-oxo-hexanoyl-homoserine lactone (3OC6-HSL) or N-3-oxo-octanoyl-homoserine lactone (3OC8-HSL) was completely abolished in plants with loss-of-function mutations in two candidate G-protein Coupled Receptors (GPCRs), Cand2 and Cand7. Furthermore, real-time PCR analysis revealed that the expression levels of Cand2 and Cand7 were elevated in plants treated with 3OC6-HSL or 3OC8-HSL. These results suggest that Cand2 and Cand7 are involved in the regulation of root growth by bacterial AHLs and that GPCRs play a role in mediating interactions between plants and microbes.


Metal-catalyzed C-S bond formation using sulfur surrogates.
Sulfur-containing compounds are present in a wide range of biologically important natural products, drugs, catalysts, and ligands and they have wide applications in material chemistry. Transition metal-catalyzed C-S bond-forming reactions have successfully overcome the obstacles associated with traditional organosulfur compound syntheses such as stoichiometric use of metal-catalysts, catalyst-poisoning and harsh reaction conditions. One of the key demands in metal-catalyzed C-S bond-forming reactions is the use of an appropriate sulfur source due to its odor and availability. The unpleasant odor of many organic sulfur sources might be one of the reasons for the metal-catalyzed C-S bond-forming reactions being less explored compared to other metal-catalyzed C-heteroatom bond-forming reactions. Hence, employing an appropriate sulfur surrogate in the synthesis of organosulfur compounds in metal-catalyzed reactions is still of prime interest for chemists. This review explores the recent advances in C-S bond formation using transition metal-catalyzed cross-coupling reactions and C-H bond functionalization using diverse and commercially available sulfur surrogates. Based on the different transition metal-catalysts, this review has been divided into three major classes namely (1) palladium-catalyzed C-S bond formation, (2) copper-catalyzed C-S bond formation, and (3) other metal-catalyzed C-S bond formation. This review is further arranged based on the different sulfur surrogates. Also, this review provides an insight into the growing opportunities in the construction of complex organosulfur scaffolds covering natural product synthesis and functional materials.


Cancer in the parents of children with cancer.
Certain types of cancer in children and young adults have been linked with an increased risk of cancer in close relatives. However, the relation between childhood cancer and familial risk remains to be fully assessed in population-based studies. We conducted a nationwide study in Denmark of 11,380 parents of children with cancer. The children were identified from records in the Danish Cancer Registry; their parents were identified from population registers. The occurrence and rate of cancer in the parents were determined with use of the Cancer Registry's files and compared with national incidence rates for various categories of tumor. Overall, 1445 cancers were diagnosed in the parents, as compared with 1496 expected from national incidence rates, to yield standardized incidence ratios of 1.0 (95 percent confidence interval, 0.9 to 1.0) for all parents, 1.0 for mothers, and 0.9 for fathers. The lower rate of cancer among fathers reflected their lower standardized incidence ratio for lung cancer (0.8; 95 percent confidence interval, 0.6 to 0.9), as calculated from 144 observations. Genetic determinants are important in several types of childhood cancer, but the genetic susceptibility to tumors does not generally extend to the parents of children with cancer, nor do the patterns of incidence point to the influence of shared environmental factors. Thus, cancer in children should not be viewed as a general marker for an increased risk of cancer in the patients' parents.


Metabolic Profiling Identified a Novel Biomarker Panel for Metabolic Syndrome-Positive Hepatocellular Cancer.
Metabolic syndrome (MetS) is an independent risk factor for hepatocellular cancer (HCC). Currently, there is no highly sensitive and specific biomarkers for HCC surveillance in MetS population. Metabolomics has been reported as a powerful technology for biomarker discovery. In the present study, we aimed to explore novel biomarkers with high sensitivity and specificity for MetS-positive [MetS(+)] HCC by metabolomic analysis. At first, many serum metabolites were found dysregulated in MetS(+) HCC individuals. Validation of the dysregulated metabolites by targeted metabolite analyses revealed that serum L-glutamic acid (L-glu), pipecolic acid (PA) and 7-methylguanine (7-mG) were increased in MetS(+) HCC compared to MetS group. Then a biomarker panel including L-glu, PA and alpha-fetoprotein (AFP) was identified as a novel biomarker for the diagnosis of MetS(+) HCC. Receiver operating characteristic (ROC) curve was drawn and the area under the ROC curve (AUC) was 0.87 for discriminating MetS(+) HCC from MetS group. The biomarker panel was capable of detecting small (AUC = 0.82) and early-stage (AUC = 0.78) tumors as well. Moreover, it exhibited great diagnostic performance (AUC = 0.93) for discriminating MetS(+) HCC from other MetS-associated cancers, including colorectal cancer and gastric cancer. Collectively, our study establishes a novel diagnostic tool for MetS(+) HCC.


Phonological-orthographic consistency for Japanese words and its impact on visual and auditory word recognition.
In most models of word processing, the degrees of consistency in the mappings between orthographic, phonological, and semantic representations are hypothesized to affect reading time. Following Hino, Miyamura, and Lupker's (2011) examination of the orthographic-phonological (O-P) and orthographic-semantic (O-S) consistency for 1,114 Japanese words (339 katakana and 775 kanji words), in the present research, we initially attempted to measure the phonological-orthographic (P-O) consistency for those same words. In contrast to the O-P and O-S consistencies, which were equivalent for kanji and katakana words, the P-O relationships were much more inconsistent for the kanji words than for the katakana words. The impact of kanji words' P-O consistency was then examined in both visual and auditory word recognition tasks. Although there was no effect of P-O consistency in the standard visual lexical-decision task, significant effects were detected in a lexical-decision task with auditory stimuli, in a perceptual identification task using masked visual stimuli, and in a lexical-decision task with degraded visual stimuli. The implications of these results are discussed in terms of the impact of P-O consistency in auditory and visual word recognition. (PsycINFO Database Record


Risk assessment following self-harm: comparison of mental health nurses and psychiatrists.
This paper is a report of a study conducted to compare risk assessments by psychiatrists and mental health nurses following an episode of self-harm. Self-harm assessments by nurses and psychiatrists are similar in terms of overall content, but risk assessment may vary by professional discipline. To our knowledge previous researchers have not compared the positive predictive value of risk assessments by nurses and psychiatrists, the factors that inform those assessments in clinical practice or the management of people assessed as being at high risk. We conducted a prospective cohort study (2002-2006) of 3491 individuals presenting with self-harm to three hospitals in the North West of England. A standard assessment form including detailed demographic and clinical data was completed by the assessing psychiatrist or nurse. The positive predictive value of risk assessments for self-harm repetition was 25% (95% CI: 20-31) among nurses and 23% (95% CI: 13-37) among psychiatrists. There was strong agreement on factors associated with high risk assessment by both professions. Following assessment of high risk, psychiatrists were much more likely than nurses to admit people for inpatient treatment (RR=5.6, 95% CI: 3.2-9.7). This difference remained highly statistically significant after controlling for case-mix differences (RR=4.3, 95% CI: 2.4-7.7). Our finding that risk assessments were comparable by profession supports the provision of nurse-led assessment services. However, inpatient admission was influenced largely by assessor type rather than patient characteristics. This has important implications for equity of care and may reflect professional differences in referral practices.


Low-molecular-weight heparin for the prevention of obstetric complications in women with thrombophilias.
To evaluate the benefit of combined low-molecular-weight (LMW) heparin and aspirin for prophylaxis in women carriers of thrombophilia who had previously suffered from severe obstetric complications. The 33 studied women had an earlier pregnancy complicated by severe preeclampsia, abruptio placentae, intrauterine growth retardation, or intrauterine fetal death. All were subsequently diagnosed as carrying inherited thrombophilias. In their subsequent pregnancy, prophylactic therapy consisting of LMW heparin 40 mg/day (Enoxaparin, Rhone-Poulenc-Rorer, France) and aspirin was administered. Patients who were found to be homozygotes for the methylenetetrahydrofolate reductase mutation also received folic acid supplementation throughout their pregnancy. Low-molecular-weight heparin was well tolerated and none of the women or the newborns developed any hemorrhagic complications. Only three (9.1%) of the women developed pregnancy complications. The mean gestational age and the mean birth weight at delivery in the previously complicated pregnancies were 32.1 +/- 5.0 weeks and 1175 +/- 590 g, respectively, compared to 37.6 +/- 2.3 weeks and 2719 +/- 526 g, respectively, in the treated pregnancies (p < 0.001). This uncontrolled trial suggests that patients with obstetric complications and an inherited thrombophilia may benefit from treatment with combined LMW heparin and aspirin in subsequent pregnancies. However, this needs to be verified by controlled trials before considering clinical application.


Interobserver Agreement in MR Enterography for Diagnostic Assessment in Patients with Crohn's Disease.
To evaluate the extent to which MRE can be used as an observer-independent, objective imaging method for the diagnosis and evaluation of CD with respect to the detection of inflammatory changes of the small bowel and lymphadenopathy as diagnostic criterion and bowel distension as a quality criterion. MRE scans of 84 patients (42 female, median age 37 years) were evaluated independently by 4 experienced radiologists. Analysis of inflammatory changes of the bowel wall, lymphadenopathy and adequate bowel distension was conducted separately for the jejunum, ileum and terminal ileum. The Kendall's W-test was used for the statistical comparison of concordance. In a total of 55 patients, inflammatory activity of the bowel wall was detected and MRE was found to have a high interobserver reproducibility concerning inflammatory changes of the intestinal wall (Kendall's W 0.527 - 0.823). Concerning lymphadenopathy (31 cases, 36.9 %), a low to moderate consensus could be shown with a Kendall's W value of 0.402 - 0.505. For the assessment of adequate bowel distension, a moderate concordance between the operators could be found (Kendall's W 0.497 - 0.581). MRE has proven high interobserver agreement with respect to the diagnosis of inflammatory disease activity of the bowel as a diagnostic criterion in patients with CD. Concerning adequate bowel distension as a quality criterion of the examination itself and lymphadenopathy as a diagnostic criterion, moderate interobserver agreement could be found. This is thought to have a rather small effect on the diagnostic significance and conclusiveness of the method in the daily routine. ▶ MR enterography as observer independent diagnostic procedure in patients with Chron's Disease. ▶ Highest interobserver concordance for the criterion of inflammatory bowel wall affection. ▶ Moderate interobserver concordance for lymphadenopathy and bowel distension.


Linear discriminant functions to improve the glaucoma probability score analysis to detect glaucomatous optic nerve heads: a multicenter study.
The purpose of the study was to create a linear discriminant function (LDF) formula by using the new Glaucoma Probability Score (GPS) global and sectorial optic nerve head parameters measured by Heidelberg Retinal Tomograph 3 to improve the GPS diagnostic capacity to discriminate between healthy and glaucomatous eyes. This is a multicenter cross-sectional study. To calculate the LDF formula, 137 normal individuals and 96 glaucomatous patients were selected. Another independent sample of 60 healthy and 69 glaucomatous eyes was used to evaluate the diagnostic accuracy of the LDF formulas. All patients underwent a full eye examination, standard achromatic perimetry by using Humphrey Field Analyzer, and imaging with Heidelberg Retinal Tomograph 3. Glaucoma was defined on the basis of SITA-24-2 visual field loss (pattern standard deviation P<5% and glaucoma Hemifield test outside normal limits). The area under the receiver operating characteristics curves and sensitivity and specificity for different LDFs were analyzed as measures of diagnostic accuracy. The analysis was repeated after stratification for optic disc size and glaucoma stage. Two LDF formulas improved GPS algorithm results. At fixed specificities of 85% and 95%, the sensitivity values were 79.7% and 71%, respectively, for the GPS-only LDF, which used only the so-called GPS parameters, whereas the values were 85.5% and 79.7%, respectively, for the GPS-RA LDF, which used sectorial rim area parameters as well. When the so-called GPS parameters were used in an LDF formula, its diagnostic capacity slightly improved; however, the diagnostic performances of the GPS LDF, which used sectorial rim area parameters as well, were better.


Predictors of tuberculosis treatment success among HIV-TB co-infected patients attending major tuberculosis treatment sites in Abeokuta, Ogun State, Nigeria.
tuberculosis (TB) is the commonest opportunistic infection and cause of death in patients with Human Immunodeficiency Virus (HIV) in developing countries. World Health Organization (WHO) recommends 85% treatment success rate for all TB cases as an indicator of TB control. The study aimed at determining TB treatment success rate among TB-HIV co-infected patients and identifying predictors of successful treatment among patients in TB treatment sites in Abeokuta, Nigeria. it was a cross-sectional study among HIV-TB co-infected patients in the two major health facilities in Abeokuta, Nigeria. Socio-demographic characteristics with treatment history were obtained using a semi-structured questionnaire. Sputum samples were collected and tested for acid-fast bacilli (AFB) using a standard method according to national guideline for TB treatment to determine treatment success rate. Treatment success was defined as any HIV positive patient with a diagnosis of TB by acid-fast bacilli (AFB) smear positivity at diagnosis, who after 6 months of complete treatment becomes smear negative. Adjusted odds ratio was used to identify independent predictors of successful treatment outcome with confidence interval set at 95% and level of significance set at P < 0.05. a total of 109 HIV-TB co-infected patients were enrolled for this study. Fifty-nine (54.1%) were females, 106 (97.3%) were newly treated for TB. Eighty-five (78.0%) were treated in a private health facility. A total of 91 had successful treatment outcome with a treatment success rate (TSR) of 83.5%. Eleven (10.1%) died, 5 (4.6%) defaulted, 1 (0.9%) failed treatment, 1 (0.9%) was transferred out. Successful treatment was associated with being newly registered (i.e. receiving TB treatment under the DOTS program for the first time), receiving TB treatment for the first time (adjusted OR = 18, 95%CI: 1.5-482.3) and being treated at a private health facility (adjusted OR = 14.1, 95%CI 4.27-48.4). treatment success rate of TB among HIV-TB co-infected patients in this study slightly falls below the WHO target. Registration status and health facility type were predictors of treatment outcome among study patients. Patients and healthcare workers in public facilities were educated on HIV-TB co-infection management.


Mealtimes in a neurological ward: a phenomenological-hermeneutic study.
To examine the environment surrounding hospital meals for patients with neurological diseases. A determined effort has been made to optimise the nutrition of hospitalised patients. However, the organisation of mealtimes and their relational and aesthetic aspects have not received similar attention. The result is that all other tasks continue with undiminished intensity when patient meals are served and eaten. Based on a qualitative design, 25 mealtime situations were systematically observed. The observations varied by time of day, date, staff and patients present. Field notes were taken on the spot, and quotes were written directly. After transcription, the text materials were analysed and interpreted using a phenomenological-hermeneutic approach inspired by the philosopher Paul Ricouer. Three main themes were identified in the analysis: eating in a railway station, creating aesthetic mealtimes in an unaesthetic atmosphere and using familiar rituals in unfamiliar surroundings. The inclusion of aesthetic elements and familiarity was found to play an important role in the desire of patients to eat. However, these elements were challenged by the design of the physical space and institutional structures. This study contributes to our understanding of the environment surrounding hospital meals for patients with neurological diseases. Based on this study, it can be concluded that meals were at a high risk of being served as a mindless task without the recognition that mealtimes are sensed with the whole body of the patient and not only by the mouth. The importance of the mealtime environment must be acknowledged because it serves as a communicative aspect for neurological patients by letting them know what to expect from the coming hospital meal.


Swelling-Resistant, Crosslinked Polyvinyl Alcohol Membranes with High ZIF-8 Nanofiller Loadings as Effective Solid Electrolytes for Alkaline Fuel Cells.
The present work investigates the direct mixing of aqueous zeolitic imidazolate framework-8 (ZIF-8) suspension into a polyvinyl alcohol (PVA) and crosslinked with glutaraldehyde (GA) to form swelling-resistant, mechanically robust and conductivity retentive composite membranes. This drying-free nanofiller incorporation method enhances the homogeneous ZIF-8 distributions in the PVA/ZIF-8/GA composites to overcome the nanofiller aggregation problem in the mixed matrix membranes. Various ZIF-8 concentrations (25.4, 40.5 and 45.4 wt.%) are used to study the suitability of the resulting GA-crosslinked composites for direct alkaline methanol fuel cell (DAMFC). Surface morphological analysis confirmed homogeneous ZIF-8 particle distribution in the GA-crosslinked composites with a defect- and crack-free structure. The increased ionic conductivity (21% higher than the ZIF-free base material) and suppressed alcohol permeability (94% lower from the base material) of PVA/40.5%ZIF-8/GA resulted in the highest selectivity among the prepared composites. In addition, the GA-crosslinked composites' selectivity increased to 1.5−2 times that of those without crosslink. Moreover, the ZIF-8 nanofillers improved the mechanical strength and alkaline stability of the composites. This was due to the negligible volume swelling ratio (<1.4%) of high (>40%) ZIF-8-loaded composites. After 168 h of alkaline treatment, the PVA/40.5%ZIF-8/GA composite had almost negligible ionic conductivity loss (0.19%) compared with the initial material. The maximum power density (Pmax) of PVA/40.5%ZIF-8/GA composite was 190.5 mW cm−2 at 60 °C, an increase of 181% from the PVA/GA membrane. Moreover, the Pmax of PVA/40.5%ZIF-8/GA was 10% higher than that without GA crosslinking. These swelling-resistant and stable solid electrolytes are promising in alkaline fuel cell applications.


The association between time to extracorporeal cardiopulmonary resuscitation and outcome in patients with out-of-hospital cardiac arrest.
Extracorporeal cardiopulmonary resuscitation (ECPR) is considered for potentially reversible out-of-hospital cardiac arrest (OHCA). However, the association between time to ECPR and outcome has not been well established. Between June 2014 and December 2017, we enrolled 34 754 OHCA patients in a multicentre, prospective fashion [Japanese Association for Acute Medicine (JAAM)-OHCA registry]. After the application of exclusion criteria, 695 OHCA patients who underwent ECPR for cardiac causes were eligible for this study. We investigated the association between the call-to-ECPR interval and favourable neurological outcome (cerebral performance category 1 or 2) at 30 days. Seventy-seven patients (11%) had a favourable neurological outcome at 30 days. The call-to-ECPR intervals in these patients were significantly shorter than in those with an unfavourable neurological outcome [49 (41-58) vs. 58 (48-68) min, respectively, P < 0.001]. A longer call-to-ECPR interval was associated with a smaller proportion of patients undergoing percutaneous coronary intervention (PCI) (P = 0.034) or target temperature management (TTM) (P < 0.001). Stepwise multivariable logistic regression analysis revealed that the call-to-ECPR interval was an independent predictor of favourable neurological outcome [odds ratio (OR) 0.96, 95% confidence interval (CI) 0.94-0.99, P = 0.001], as were age, male gender, initial shockable rhythm, transient return of spontaneous circulation in the prehospital setting, arterial pH at hospital arrival, PCI (OR 2.30, 95% CI 1.14-4.66, P = 0.019), and TTM (OR 2.28, 95% CI 1.13-4.62, P = 0.019). A shorter call-to-ECPR interval and implementation of PCI and TTM predicted a favourable neurological outcome at 30 days in OHCA patients who underwent ECPR for cardiac causes.


Hyperaminoaciduria identifies patients at risk of developing renal tubular toxicity associated with ifosfamide and platinate containing regimens.
We monitored renal tubular function in 18 neuroblastoma patients treated with chemotherapeutic regimens containing Ifosfamide and platinates. The total IFO dose ranged from 30 to 48 g/m2. After each IFO course and at regular intervals during follow-up 24 hour urinary exception of aminoacids, qualitative excretion of protein and glucose, tubular reabsorption of phosphate, serum pH, and liver enzyme (SGOT and SGPT) were measured. The ratio of alpha-amino-Nitrogen/total-Nitrogen (normal less than 2.5%) and the urinary excretion pattern were used to quantify the aminoaciduria in 12 out of 15 evaluable patients some degree of tubular toxicity occurred during treatment, slowly progressing to a Debré-de Toni-Fanconi syndrome (DTFS) in 7 patients. The DTFS was fully developed in most cases 3-9 months after the end of treatment and was reversible in 3 cases. Hyperaminoaciduria (HAA) occurred in all patients during treatment, preceding other signs of tubular toxicity. The maximum ratio measured before development of a DTFS was significantly higher in the patients with severe toxicity (P less than .01). HAA characterized by a ratio greater than 10% predicts the development of a DTFS with a sensitivity of 71.4% and a specificity of 87.4%.


Perception of human motion.
Humans, being highly social creatures, rely heavily on the ability to perceive what others are doing and to infer from gestures and expressions what others may be intending to do. These perceptual skills are easily mastered by most, but not all, people, in large part because human action readily communicates intentions and feelings. In recent years, remarkable advances have been made in our understanding of the visual, motoric, and affective influences on perception of human action, as well as in the elucidation of the neural concomitants of perception of human action. This article reviews those advances and, where possible, draws links among those findings.


[Systemic lupus erythematosus presenting as autoimmune parotitis and pancreatitis - Case Report].
Systemic lupus erythematosus (SLE) is a multiorgan autoimmune disease which can present from classical to atypical forms. We discuss the case of a young lady of 29 years-old recently diagnosed with SLE that manifested parotitis and pancreatitis.


Primary Neuroendocrine Tumor of the Parotid Gland: A Case Report and a Comprehensive Review of a Rare Entity.
Neuroendocrine tumors (NETs) comprise a heterogeneous group of malignancies from cells derived from the neural crest with neuroendocrine differentiation. Despite the differences in the site of origin, nomenclature, biological behavior, and functional status, NETs share certain ultrastructural and immunohistochemical features. NETs are relative rare tumors with an annual incidence of 5.76 new cases per 100.000 inhabitants and they usually appear in the gastrointestinal tract or in the pulmonary system. Head and neck NETs are uncommon with limited information regarding frequency, most of them showing small cell carcinoma features. NETs that arise from the salivary glands are exceedingly rare. Regardless of their low frequency, it is imperative to accurately differentiate these tumors from the much more common squamous cell carcinomas and from metastasis from another primary tumor due to the completely different therapeutic approaches and prognosis. The diagnosis is based on the recognition of the typical neuroendocrine architecture and immunohistochemical staining and on an exhaustive work-up. Hereby, we report a case of a moderately differentiated NET of the parotid gland that was treated with a complete parotidectomy. We summarize the clues that led to the final diagnosis and major strategies that were employed to manage the patient. We also perform a comprehensive review of the scarce available literature on this topic.


[A study of the protective effect of the DNA vaccine encoding tubercle antigen 85B with MPT64 in mice challenged with Mycobacterium tuberculosis].
To explore the protective effect of the DNA vaccine encoding Mycobacterium tuberculosis Ag85B with MPT64 in mice infected with Mycobacterium tuberculosis. Fifty four C57BL/6 mice were randomized into six groups and subjected to the following treatments respectively: intramuscularly immunized with PBS, pcDNA3.1, BCG, pcDNA/Ag85B, pcDNA/MPT64 and pcDNA/Ag85B + pcDNA/MPT64 on three occasions at 3-week intervals. The BCG group received a single subcutaneous injection of 1 x 10(6) CFU BCG. The mice were challenged with 10(6) CFU H(37)Rv via lateral tail vein 35 days later after the third immunization for DNA vaccine groups and 100 days later for BCG vaccinated group. The mice in vaccinated groups and control groups were sacrificed 42 days later following challenge. The lungs and spleens were removed, and the number of CFU in organs and histopathologic changes were determined. The antibody level, IFN-gamma, IL-4 and the survival time in all of the mice were evaluated. The number of bacterial colonies in the lungs and spleens were lg(-1) (7.854 +/- 0.003) CFU/g and lg(-1) (7.190 +/- 0.016) CFU/g in PBS group, lg(-1) (7.700 +/- 0.016) CFU/g and lg(-1) (7.072 +/- 0.068) CFU/g in pcDNA3.1 group, lg(-1) (6.449 +/- 0.002) CFU/g and lg(-1) (5.436 +/- 0.042) CFU/g in BCG group, lg(-1) (7.370 +/- 0.002) CFU/g and lg(-1) (6.430 +/- 0.009) CFU/g in pcDNA/Ag85B group, lg(-1) (7.547 +/- 0.003) CFU/g and lg(-1) (6.784 +/- 0.002) CFU/g in pcDNA/MPT64 group, and lg(-1) (6.918 +/- 0.002) CFU/g and lg(-1) (6.079 +/- 0.004) CFU/g in pcDNA/Ag85B + pcDNA/MPT64 group respectively, which showed significant decrease at 6th week postchallenge in all the vaccinated groups (P < 0.05), especially in BCG group (P < 0.01). Antibody titer of pcDNA/Ag85B + pcDNA/MPT64 group and pcDNA/Ag85B group was higher than that of the other groups (P < 0.05). The level of IFN-gamma produced by spleen lymphocytes and spleen lymphocyte proliferation from BCG group, pcDNA/Ag85B + pcDNA/MPT64 group was higher than that of the other groups (P < 0.05). No IL-4 was detected in all groups. The pulmonary histopathological changes were observed 6 weeks later following challenge with Mycobacterium tuberculosis H(37)Rv. In PBS and pcDNA3.1 groups, the lesion was characterized by inflammatory infiltration and lung tissue necrosis, in BCG group by granulomas and numerous macrophages, lymphocytes and a few epithelioid cells. The lesion in pcDNA/Ag85B group was characterized by serofibrous inflammatory infiltration and a few macrophages, in pcDNA/Ag85B + pcDNA/MPT64 group, by granulomas, numerous macrophages and lymphocytes. The lesion in spleen was different from the lung and characterized by proliferative lymphocytes and inflammatory infiltration. The results in spleen were similar to those in the lung. The survival time of BCG vaccinated mice after challenge with Mycobacterium tuberculosis H(37)Rv was longer than that of the other groups. The survival time of pcDNA/Ag85B + pcDNA/MPT64 group was longer than that of other DNA vaccine groups. The protective effect of BCG was more significant than the other groups, while the effect of pcDNA/Ag85B + pcDNA/MPT64 was better than other DNA vaccines.


Iron necessity: the secret of Wolbachia's success?
The bacterium Wolbachia (order Rickettsiales) is probably the world's most successful vertically-transmitted symbiont, distributed among a staggering 40% of terrestrial arthropod species. Wolbachia has great potential in vector control due to its ability to manipulate its hosts' reproduction and to impede the replication and dissemination of arboviruses and other pathogens within haematophagous arthropods. In addition, the unexpected presence of Wolbachia in filarial nematodes of medical and veterinary importance has provided an opportunity to target the adult worms of Wuchereria bancrofti, Onchocerca volvulus, and Dirofilaria immitis with safe drugs such as doxycycline. A striking feature of Wolbachia is its phenotypic plasticity between (and sometimes within) hosts, which may be underpinned by its ability to integrate itself into several key processes within eukaryotic cells: oxidative stress, autophagy, and apoptosis. Importantly, despite significant differences in the genomes of arthropod and filarial Wolbachia strains, these nexuses appear to lie on a continuum in different hosts. Here, we consider how iron metabolism may represent a fundamental aspect of host homeostasis that is impacted by Wolbachia infection, connecting disparate pathways ranging from the provision of haem and ATP to programmed cell death, aging, and the recycling of intracellular resources. Depending on how Wolbachia and host cells interact across networks that depend on iron, the gradient between parasitism and mutualism may shift dynamically in some systems, or alternatively, stabilise on one or the other end of the spectrum.


Metahyphopichia laotica gen. nov., sp. nov., a polymorphic yeast related to Hyphopichia.
Four strains alternating between yeast and filamentous growth morphologies were isolated from flowers in two regions of Laos. In liquid environment the isolates propagated by budding and developed irregularly shaped pseudohyphae. On solid media, their yeast cells switched to hyphal growth which could return to the yeast phase by developing lateral blastoconidia. The sequences of the D1/D2 domains of the large subunit (LSU) 26S rRNA genes, the internal transcribed spacer (ITS) regions and the small subunit (SSU) 18S rRNA genes were identical in the four strains and differed from the corresponding sequences of other yeast species available in databases by at least 11 % (D1/D2), 13 % (ITS) and 7 % (SSU). In an independent project, two strains with D1/D2 and ITS sequences very similar to those of the Laotian strains were found in bark samples collected in Brazil. The six strains also differed from the closest yeast species in physiological properties, indicating that they represented a hitherto undescribed species. Phylogenetic analysis of the D1/D2 sequences, and the concatenated sequences of the SSU rRNA genes, D1/D2 domains of LSU rRNA genes as well as the protein-encoding genes ACT1 and TEF1 placed thestrains close to Hyphopichia. To reflect this position, the novel genus name Metahyphopichia gen. nov. and the novel species name Metahyphopichia laotica gen. nov., sp. nov. are proposed for them. The type strain of the type species is 11-1006T(=CBS 13022T=CCY 092-001-001T=NCAIM Y.02126T) and was isolated in Luang Prabang (Laos). MycoBank registration numbers are MB 808253 (Metahyphopichia) and MB 808254 (Metahyphopichia laotica).


[The relationship between keratoconus and axial myopia].
To study the relationship between keratoconus and axial myopia. We prospectively studied refraction and ocular biometry in 100 consecutive keratoconus eyes, and 100 emmetropic eyes. Biometric data (including posterior segment length) were obtained by A-scan ultrasound, Orbscan, and ultrasonic pachymetry. Biometric measurements were compared in both groups. Anterior chamber depth, posterior segment length and axial length were significantly different between the two groups (p<0.001). Axial length was significantly greater in the keratoconus group than in the emmetropic group (23.97 mm versus 23.21 mm, p<0.001). Posterior segment length was significantly greater in the keratoconus group than in the emmetropic group (16.54 mm versus 15.99 mm, p<0.001). In the keratoconus group, the posterior segment length and the subjective spherical equivalent were significantly correlated (rs=-0.45, p<0.001). The increase in posterior segment length in the keratoconus group and the correlation between posterior segment length and spherical equivalent in the keratoconus group suggest a statistical relationship between keratoconus and axial myopia.