Selective heparinization of venous anastomosis in latissimus dorsi free flaps to cover lower-extremity soft-tissue defects.
Two groups of consecutive patients treated with latissimus dorsi free myocutaneous flaps to cover lower-extremity soft-tissue defects were compared for postoperative vascular occlusion. In the first group of 13 patients (group I), there were five (38%) venous occlusions and no arterial occlusions. The second group of 15 patients (group II) was treated with selective heparinization of each venous anastomosis via a 0.35" catheter sutured into the serratus branch of the donor vein. In this group one patient suffered an arterial occlusion, but no patient suffered a venous occlusion. Statistical analysis using the Fisher exact probabilities test showed a significant decrease in vascular occlusion rate in group II, proving that selective heparinization had a beneficial effect on the venous patency rate.


Intelligent Fault Diagnosis and Forecast of Time-Varying Bearing Based on Deep Learning VMD-DenseNet.
Rolling bearings are important in rotating machinery and equipment. This research proposes variational mode decomposition (VMD)-DenseNet to diagnose faults in bearings. The research feature involves analyzing the Hilbert spectrum through VMD whereby the vibration signal is converted into an image. Healthy and various faults show different characteristics on the image, thus there is no need to select features. Coupled with the lightweight network, DenseNet, for image classification and prediction. DenseNet is used to build a model of motor fault diagnosis; its structure is simple, and the calculation speed is fast. The method of using DenseNet for image feature learning can perform feature extraction on each image block of the image, providing full play to the advantages of deep learning to obtain accurate results. This research method is verified by the data of the time-varying bearing experimental device at the University of Ottawa. Through the four links of signal acquisition, feature extraction, fault identification, and prediction, a mechanical intelligent fault diagnosis system has established the state of bearing. The experimental results show that the method can accurately identify four common motor faults, with a VMD-DenseNet prediction accuracy rate of 92%. It provides a more effective method for bearing fault diagnosis and has a wide range of application prospects in fault diagnosis engineering. In the future, online and timely diagnosis can be achieved for intelligent fault diagnosis.


Imaging mass spectrometry of three-dimensional cell culture systems.
Three-dimensional (3D) cell cultures have increased complexity compared to simple monolayer and suspension cultures, recapitulating the cellular architecture and molecular gradients in tissue. As such, they are popular for in vitro models in biological research. Classical imaging methodologies, like immunohistochemistry, are commonly used to examine the distribution of specific species within the spheroids. However, there is a need for an unbiased discovery-based methodology that would allow examination of protein/peptide distributions in 3D culture systems, without a need for prior knowledge of the analytes. We have developed a matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS)-based imaging approach to examine protein distributions in 3D cell culture models. Using colon carcinoma cell lines, we detect changes in the spatial distribution of proteins across 3D culture structures. To identify the protein species present, we are combining results from the MS/MS capabilities of MALDI-MS to sequence peptides in a de novo fashion and nanoflow liquid chromatography-tandem mass spectrometry (nLC-MS/MS) of homogenized cultures. As a proof-of-principle, we have identified cytochrome C and Histone H4 as two of the predominant protein species in the 3D colon carcinoma cultures.


Cardiac Disease of Raptors.
Cardiac disease, in its various presentations, is being recognized as a common raptor health problem. Evidence suggests that the prevalence of cardiac disease varies between captive and wild bird of prey populations, probably because of differences in activity levels and diet. However, a wide variety of cardiovascular diseases have been reported to affect raptor species (captive and free living), including atherosclerosis, pathogenic arrhythmias, infectious cardiomyopathies, and endocarditis. Diagnostic testing used to identify cardiac abnormalities include radiographic imaging, electrocardiogram, echocardiogram, and computed tomography angiograms. Information pertaining to therapeutic treatment for raptor cardiac disease patients is inadequate or has not been investigated. This review of cardiac disease will provide current information regarding cardiac diseases that are diagnosed in birds of prey, diagnostic testing, and treatment options.


The demography of infertility in the United States.
"Some popular descriptions of infertility have suggested that there are nine or ten million infertile couples, that one in six couples is infertile, that infertility is increasing rapidly, or that there is an 'epidemic' of infertility in the USA.... The purpose of this chapter is to determine whether these perceptions are accurate and if not, to suggest why there is a perception that infertility is epidemic.... We report two measures of infertility here. The first is called 'impaired fecundity' and is derived from a series of direct survey questions...on the ability to have children. The second is 'infertility status' among married couples." Data are from the National Survey of Family Growth for 1976, 1982, and 1988. Data for 1965 are from the National Fertility Study.


Effects of age and gender on discrete and reciprocal aiming movements.
Using a cross-sectional design, this study determined the time course of aging effects on rapid discrete and reciprocal aiming movements in men and women. A total of 80 men and 61 women in good health were classified into six age groups (25, 35, 45, 55, 65, and 75 years). The discrete task required participants to make one discrete aiming movement, whereas the reciprocal task required a series of back-and-forth movements. Results indicated for both aiming tasks that greater age was strongly associated with slower movement times. The significant interaction between age and task indicated that the discrete task showed much larger aging effects (54%) than the reciprocal task (25%). This finding is tentatively interpreted in terms of a reduced efficiency of "on-line" control processes.


Simultaneous multianalyte detection with a nanometer-scale pore.
It was recently shown that naturally occurring, genetically engineered or chemically modified channels can be used to detect analytes in solution. We demonstrate here that the overall range of analytes that can be detected by single nanometer-scale pores is expanded using a potentially simpler system. Instead of attaching recognition elements to a channel, they are covalently linked to polymers that otherwise thread through a nanometer-scale pore. Because the rate of unbound polymer entering the pore is proportional to its concentration in the bulk, the binding of analyte to the polymer alters the latter's ability to thread through the pore, and the signal that results from individual polymer translocation is unique to the polymer type; the method permits multianalyte detection and quantitation. We demonstrate here that two different proteins can be simultaneously detected with this technique.


A report from the World Transplant Congress 2014 (July 27-31 - San Francisco, California, USA).
The largest meeting in the field of transplant science, the World Transplant Congress 2014 in San Francisco, attracted scientists in the area from across the world in a joint effort by the three organizing societies: American Society of Transplant Medicine, the Transplantation Society and the American Society of Transplantation. Besides courses, symposia and networking activities, four major poster sessions and four days of oral abstract sessions dedicated to discussing advances in the area of transplantation, including notably, scientific reports on investigational and experimental approaches to immunosuppression and additional medical and pharmacological approaches to facilitate organ procurement and graft engraftment and survival in transplant donors and recipients.


SEECancer: a resource for somatic events in evolution of cancer genome.
Cancer cells progressively evolve from a premalignant to a malignant state, which is driven by accumulating somatic alterations that confer normal cells a fitness advantage. Improvements in high-throughput sequencing techniques have led to an increase in construction of tumor phylogenetics and identification of somatic driver events that specifically occurred in different tumor progression stages. Here, we developed the SEECancer database (http://biocc.hrbmu.edu.cn/SEECancer), which aims to present the comprehensive cancer evolutionary stage-specific somatic events (including early-specific, late-specific, relapse-specific, metastasis-specific, drug-resistant and drug-induced genomic events) and their temporal orders. By manually curating over 10 000 published articles, 1231 evolutionary stage-specific genomic events and 5772 temporal orders involving 82 human cancers and 23 tissue origins were collected and deposited in the SEECancer database. Each entry contains the somatic event, evolutionary stage, cancer type, detection approach and relevant evidence. SEECancer provides a user-friendly interface for browsing, searching and downloading evolutionary stage-specific somatic events and temporal relationships in various cancers. With increasing attention on cancer genome evolution, the necessary information in SEECancer will facilitate understanding of cancer etiology and development of evolutionary therapeutics, and help clinicians to discover biomarkers for monitoring tumor progression.


Hadamard editing of glutathione and macromolecule-suppressed GABA.
The primary inhibitory neurotransmitter γ-aminobutyric acid (GABA) and the major antioxidant glutathione (GSH) are compounds of high importance for the function and integrity of the human brain. In this study, a method for simultaneous J-difference spectral-edited magnetic resonance spectroscopy (MRS) of GSH and GABA with suppression of macromolecular (MM) signals at 3 T is proposed. MM-suppressed Hadamard encoding and reconstruction of MEGA (Mescher-Garwood)-edited spectroscopy (HERMES) consists of four sub-experiments (TE = 80 ms), with 20-ms editing pulses applied at: (A) 4.56 and 1.9 ppm; (B) 4.56 and 1.5 ppm; (C) 1.9 ppm; and (D) 1.5 ppm. One Hadamard combination (A + B - C - D) yields GSH-edited spectra, and another (A - B + C - D) yields GABA-edited spectra, with symmetric suppression of the co-edited MM signal. MM-suppressed HERMES, conventional HERMES and separate Mescher-Garwood point-resolved spectroscopy (MEGA-PRESS) data were successfully acquired from a (33 mm)3 voxel in the parietal lobe in 10 healthy subjects. GSH- and GABA-edited MM-suppressed HERMES spectra were in close agreement with the respective MEGA-PRESS spectra. Mean GABA (and GSH) estimates were 1.10 ± 0.15 i.u. (0.59 ± 0.12 i.u.) for MM-suppressed HERMES, and 1.13 ± 0.09 i.u. (0.66 ± 0.09 i.u.) for MEGA-PRESS. Mean GABA (and GSH) differences between MM-suppressed HERMES and MEGA-PRESS were -0.03 ± 0.11 i.u. (-0.07 ± 0.11 i.u.). The mean signal-to-noise ratio (SNR) improvement of MM-suppressed HERMES over MEGA-PRESS was 1.45 ± 0.25 for GABA and 1.32 ± 0.24 for GSH. These results indicate that symmetric suppression of the MM signal can be accommodated into the Hadamard editing framework. Compared with sequential single-metabolite MEGA-PRESS experiments, MM-suppressed HERMES allows for simultaneous edited measurements of GSH and GABA without MM contamination in only half the scan time, and SNR is maintained.


Bayesian semiparametric estimation of covariate-dependent ROC curves.
Receiver operating characteristic (ROC) curves are widely used to measure the discriminating power of medical tests and other classification procedures. In many practical applications, the performance of these procedures can depend on covariates such as age, naturally leading to a collection of curves associated with different covariate levels. This paper develops a Bayesian heteroscedastic semiparametric regression model and applies it to the estimation of covariate-dependent ROC curves. More specifically, our approach uses Gaussian process priors to model the conditional mean and conditional variance of the biomarker of interest for each of the populations under study. The model is illustrated through an application to the evaluation of prostate-specific antigen for the diagnosis of prostate cancer, which contrasts the performance of our model against alternative models.


Transient response of serpinA3 during cellular stress.
We demonstrated that serpinA3c/k relocates from the cytoplasm to the apical tubular membrane (ATM) in chronic kidney disease (CKD), suggesting its secretion in luminal space in pathophysiological contexts. Here, we studied serpinA3c/k expression and secretion under different stressful conditions in vitro and in vivo. HEK-293 cells were transfected with a FLAG-tagged serpinA3c/k clone and exposed to H2 O2 or starvation. Both stressors induced serpinA3c/k secretion but with a higher molecular weight. Glycanase treatment established that serpinA3c/k is glycosylated. Site-directed mutagenesis for each of the four glycosylation sites was performed. During cellular stress, serpinA3c/k secretion increased with each mutant except in the quadruple mutant. In rats and patients suffering acute kidney injury (AKI), an atypical urinary serpinA3c/k excretion (uSerpinA3c/k) was observed. In rats with AKI, the greater the induced kidney damage, the greater the uSerpinA3 c/k, together with relocation toward ATM. Our findings show that: (1) serpinA3c/k is glycosylated and secreted, (2) serpinA3c/k secretion increases during cellular stress, (3) its appearance in urine reveals a pathophysiological state, and (4) urinary serpinA3 excretion could become a potential biomarker for AKI.


Modulation of G(ialpha(2)) signaling by the axonal guidance molecule UNC5H2.
The G protein, G(ialpha(2)), regulates a number of cellular functions including cell migration, proliferation, and differentiation. The transduction of signal depends on the ability of the alpha subunit to cycle between a GDP bound and an active GTP bound state capable of interacting with intracellular enzymes. Here, we now report the novel interaction of gip2 (constitutively activated G(ialpha(2))) with the cytoplasmic domain of UNC5H2. Like G(ialpha(2)), we found that UNC5H2 is widely expressed particularly in cells which migrate. UNC5H2 binds G(ialpha(2)) when it is charged with GTP. The interaction of G(ialpha(2)) and UNC5H2 liberated adenylyl cyclase from G(ialpha(2)) inhibition. Thus, by sequestering the alpha subunit, UNC5H2 is a novel inhibitor of G(ialpha(2)) thereby increasing intracellular cAMP levels. The expression of UNC5H2 in the brain and immune system suggests that this novel inhibitor of G protein signaling may have broad significance for axonal guidance and chemotaxis.


Acute myelomonocytic leukaemia with 11q23 abnormality during multiple myeloma: is this related to anthracycline?
The clinical course of a 66-year-old man diagnosed with multiple myeloma is described. Chemotherapy including alkylating agents had no effect, and so he was treated with vincristine, doxorubicin, and dexamethasone. His bone tumor was treated with localized radiation after two courses of chemotherapy. After these treatments, monocytosis was found and dysplastic changes were noted in the bone marrow. A cytogenetic study revealed t(9;11)(p22;q23), an abnormality which had previously been absent. A diagnosis of myelodysplastic syndrome (MDS) was newly established, and transformation to acute non-lymphocytic leukaemia (ANLL) was observed 6 months later. The cumulative doses of melphalan, cyclophosphamide, doxorubicin, and radiation therapy were 432 mg, 4,200 mg, 120 mg, and 4,000 cGy, respectively. The cytogenetic abnormality suggested that this patient's MDS/ANLL was related to doxorubicin and not talk to alkylating agents, although the dose of doxorubicin administered was quite low.


Anaerobic degradation pathway of linear Alkylbenzene sulfonates (LAS) in sulfate-reducing marine sediments.
Linear alkylbenzene sulfonates (LAS) are among the principal synthetic surfactants used worldwide. Their presence in the environment has been reported in a significant number of studies, and it has been generally assumed that LAS are not biotransformed in the absence of oxygen. However, laboratory experiments performed by our group using anoxic marine sediments have reported LAS degradation percentages that can reach up to 79% in 165 days. Here, we show for the first time the initial reaction metabolites (generated via fumarate addition to the LAS molecules), their biotransformation into sulfophenyl carboxylic acids (SPC), and the progressive degradation of these by successive beta-oxidation reactions. Advanced mass spectrometry has been used to carry out the identification of these compounds. This is the first time that an anaerobic degradation pathway for LAS is described, and these results represent a significant advance in understanding the final fate of these and other similar compounds in anoxic environments.


[Rictor/mTORC2 regulates blood-testis barrier and spermatogenesis in mice].
To investigate the role of Rictor/mTORC2 in the formation of blood testis barrier (BTB), testicular development, and spermatogenesis. Amh Cre positive mice homozygous for rictor loxP with Sertoli cell specific deletion of rictor were obtained by cross breeding Amh Cre mice with rictor loxP mice. The histology of the reproductive organs, seminiferous tubules and epididymis of the transgenic mice was observed with HE staining. The cell subgroups of the germ cells in the seminiferous tubule were detected by flow cytometry with propidium iodide labeling. The expression levels of Ki 67 and separase were detected with immunofluorescence assay, and the expression levels of BTB associated proteins were detected with immunofluorescence and Western blotting. Compared with the control (Amh Cre-, rictorloxP/loxP or rictorloxP/-) mice, the mice with Sertoli cell specific rictor deletion showed significantly decreased testicular weight and epididymis weight (P<0.05), significantly increased diploid cells (P<0.01), and decreased haploid cells (P<0.01) but comparable tetraploid cells and similar expression levels of Ki 67 and separase. The mice with rictor knockout also showed aberrant localization of BTB associated proteins, which were scattered over the whole seminiferous epithelium, but the expression levels of the protein remained stable. Rictor in testicular Sertoli cells is essential for maintaining BTB integrity and function and ensuring normal spermatogenesis in mice.


The effects of reactive site location on the inhibitory properties of the serpin alpha(1)-antichymotrypsin.
The large size of the serpin reactive site loop (RSL) suggests that the role of the RSL in protease inhibition is more complex than that of presenting the reactive site (P1 residue) to the protease. This study examines the effect on inhibition of relocating the reactive site (Leu-358) of the serpin alpha(1)-antichymotrypsin either one residue closer (P2) or further (P1') from the base of the RSL (Glu-342). alpha(1)-Antichymotrypsin variants were produced by mutation within the P4-P2' region; the sequence ITLLSA was changed to ITLSSA to relocate the reactive site to P2 (Leu-357) and to ITITLS to relocate it to P1' (Leu-359). Inhibition of the chymotrypsin-like proteases human chymase and chymotrypsin and the non-target protease human neutrophil elastase (HNE) were analyzed. The P2 variant inhibited chymase and chymotrypsin but not HNE. Relative to P1, interaction at P2 was characterized by greater complex stability, lower inhibition rate constants, and increased stoichiometry of inhibition values. In contrast, the P1' variant inhibited HNE (stoichiometry of inhibition = 4) but not chymase or chymotrypsin. However, inhibition of HNE was by interaction with Ile-357, the P2 residue. The P1' site was recognized by all proteases as a cleavage site. Covalent-complexes resistant to SDS-PAGE were observed in all inhibitory reactions, consistent with the trapping of the protease as a serpin-acyl protease complex. The complete loss in inhibitory activity associated with lengthening the Glu-342-reactive site distance by a single residue and the enhanced stability of complexes associated with shortening this distance by a single residue are compatible with the distorted-protease model of inhibition requiring full insertion of the RSL into the body of the serpin and translocation of the linked protease to the pole opposite from that of encounter.


WNT1-inducible signaling protein-1 mediates TGF-β1-induced renal fibrosis in tubular epithelial cells and unilateral ureteral obstruction mouse models via autophagy.
Renal fibrosis is a common pathway for the progression of all chronic kidney diseases to end-stage kidney disease. Studies show that WNT1-inducible signaling pathway protein-1 (WISP-1) is involved in the fibrosis of various organs. The aim of the study was to explore the functional role and potential mechanism of WISP-1 in renal fibrosis. We observed that overexpression of WISP-1 in rat tubular epithelial cells (TECs) enhanced transforming growth factor-β1 (TGF-β1)-induced production of fibrotic markers, including collagen I (Col I), fibronectin (FN) and TGF-β1, while inhibition of WISP-1 suppressed such production. In vivo, the messenger RNA and protein levels of Col I, FN, and α-smooth muscle actin were significantly inhibited after anti-WISP-1 antibody treatment for 7 days in unilateral ureteral obstruction mouse models. Moreover, blockade of WISP-1 by anti-WISP-1 antibody significantly reduced autophagy-related markers, including anti-microtubule-associated protein-1 light chain 3 (LC3) and beclin 1, while increasing sequestosome 1. In addition, overexpression of WISP-1 in TECs increased autophagy as evidenced by greater numbers of GFP-LC3 puncta and increased expression of LC3 and beclin 1 in response to TGF-β1. In contrast, knockdown of WISP-1 by small interfering RNA decreased the number of GFP-LC3 puncta and the expression of LC3 and beclin 1 in TGF-β1-treated TECs. Collectively, these data suggest that WISP-1, as a profibrotic protein, may mediate renal fibrosis by inducing autophagy in both obstructive nephropathy and TGF-β1-treated TECs. WISP-1 may serve as an effective therapeutic target for the treatment of renal fibrosis.


Cervical spine anomalies in the craniosynostosis syndromes.
Cervical spine radiographs of 34 patients with a variety of craniosynostosis syndromes were reviewed to determine the incidence and nature of skeletal anomalies and to evaluate the findings in terms of syndromal patterns. Intervertebral fusions occurred in 30 percent of Pfeiffer's, 38 percent of Crouzon's, and 71 percent of Apert's syndrome children. In Crouzon's and Pfeiffer's syndromes, isolated upper cervical fusions were most common; in Apert's syndrome, the fusions were more likely to be complex involving C5-C6. This syndromal variation, however, was not specific enough for diagnostic differentiation.


The Complex Interplay between Metabolic Reprogramming and Epigenetic Alterations in Renal Cell Carcinoma.
Renal cell carcinoma (RCC) is the most common malignancy affecting the kidney. Current therapies are mostly curative for localized disease, but do not completely preclude recurrence and metastization. Thus, it is imperative to develop new therapeutic strategies based on RCC biological properties. Presently, metabolic reprograming and epigenetic alterations are recognized cancer hallmarks and their interactions are still in its infancy concerning RCC. In this review, we explore RCC biology, highlighting genetic and epigenetic alterations that contribute to metabolic deregulation of tumor cells, including high glycolytic phenotype (Warburg effect). Moreover, we critically discuss available data concerning epigenetic enzymes' regulation by aberrant metabolite accumulation and their consequences in RCC emergence and progression. Finally, we emphasize the clinical relevance of uncovering novel therapeutic targets based on epigenetic reprograming by metabolic features to improve treatment and survival of RCC patients.


crAssphage is not associated with diarrhoea and has high genetic diversity.
crAssphage is a newly discovered gut bacteriophage. However, its pathogenicity and molecular epidemiology in humans are as yet unclear. In this study, we investigated the association between crAssphage and diarrhoea, as well as the molecular epidemiology of crAssphage in Chinese patients from our hospital. Our results indicated that there were no significant differences in the crAssphage-positive ratio and viral loads in faecal supernatants between adults with diarrhoea and healthy adults. Of infants and children with diarrhoea, 2·8% were found to be crAssphage-positive, including two infants aged <1 month. Markedly, of all confirmed crAssphage-positive strains, 100% had the ORF00039 deletion and 77·8% had low identity of ORF00018 compared to crAssphage (GenBank accession no. NC_024711, designated genotype 1). Thus, crAssphage was not associated with diarrhoea and most strains of crAssphage in Chinese patients (designated genotype 2) were characterized by the ORF00039 deletion and low identity of ORF00018.


MicroRNA-23a regulates epithelial-to-mesenchymal transition in endometrial endometrioid adenocarcinoma by targeting SMAD3.
To investigate the role of total cellular microRNA (miRNA) in regulating epithelial-to-mesenchymal transition (EMT) during human endometrial endometrioid adenocarcinoma (EEC). A miRCURY LNA microRNA array was used to evaluate the miRNA profiles of human EEC tissues and corresponding nontumorous endometriums. An in vitro model of TGF-β induced EMT in HEC-1-A cells was used to investigate the role of miRNAs in the EEC during EMT. The expression of SMAD3, SMAD5, and a panel of EMT markers was detected by Western blot and quantitative PCR. The results of miRNA profiling in human EEC tissues and corresponding nontumorous endometriums demonstrated that miR-23a expression was down-regulated. Using bioinformatics, we identified SMAD3 or SMAD5 maybe as a predicted target of miR-23a. The results of luciferase reporter assay showed miR-23a directly targets and down-regulates human SMAD3 protein levels, not SMAD5 protein levels. Furthermore, overexpression of miR-23a in HEC-1-A cells increased E-cadherin expression and decreased the expression of vimentin and alpha smooth muscle actin, markers of mesenchymal cellular phenotype. Our data provide firm evidence of a role for miR-23a in the direct regulation of EMT through its targeting of SMAD3. Due to its ability to repress the EMT, miR-23a may be a novel target for EER therapeutic intervention.


[Living with the diagnosis of malignant hyperthermia].
This is the summary of a special lecture presented by a malignant hyperthermia (MH) patient at 24th Japanese Symposium of Malignant Hyperthermia in Yamagata City (August 25, 2001). Thirteen years ago, he developed acute crisis of MH on general anesthesia for tonsillectomy and was diagnosed as MH-susceptible (MHS) with muscle biopsy test. His personal troublesome experiences related to MHS, i.e. local anesthesia, sports under hot environment etc., have presented him with many difficulties and problems to be solved in actual life after discharge from hospital. He hoped in the lecture for advances in noninvasive diagnosis for MHS and safe anesthetic method for MHS-patients. Important missions of anesthesiologists include consultation of the medical problems of MHS patients and supporting their safety in daily life.


Synthesis and Structural Characterization of a Pure ZnAl4(OH)12(SO4)·2.6H2O Layered Double Hydroxide.
The phase purity of a series of ZnAl4(OH)12SO4· nH2O layered double hydroxides (ZnAl4-LDH) obtained from a reaction of bayerite (Al(OH)3) with an excess of zinc(II) sulfate under hydrothermal conditions was investigated as a function of the reaction temperature, the duration of the hydrothermal treatment, and the zinc(II) concentration. The product quality, i.e., crystalline impurities, Al impurities, and bulk Zn:Al ratio, were assessed by powder X-ray diffraction (PXRD), 27Al MAS NMR, and elemental analysis. Structural characterization of a stoichiometric ZnAl4-LDH (120 °C, 9 days, and 2.8 M Zn(II)) showed a well-defined structure of the metal ion layer as evidenced by a single, well-defined Zn environment: i.e., no Zn substitution on the Al sites according to Zn k-edge EXAFS and PXRD. Furthermore, nearly all of the 12 different 1H atoms in the -OH groups and 4 27Al resonances could be assigned using 1H,27Al NMR correlation experiments recorded with ultrafast MAS. The interlayer water content is variable on the basis of thermogravimetric analysis and changes in the 1H MAS NMR spectra with temperature. A composition of ZnAl4(OH)12(SO4)·2.6H2O was obtained from a combination of these techniques and confirmed that ZnAl4-LDH is isostructural with the mineral nickelalumite (NiAl4(OH)12SO4·3H2O).


Effects of Fumed Silica and Draw Ratio on Nanocomposite Polypropylene Fibers.
Hydrophylic fumed silica AR974 was tested as a potential nanofiller for the production of composite isotactic polypropylene filaments/fibers (containing 0.25⁻2 vol % of nanoparticles) via melt compounding and subsequent hot drawing. The objectives of this study were as follows: (i) to investigate the effects of the composition and the processing conditions on the microstructure and the thermal and mechanical properties of the produced fibers; (ii) to separate the effects of silica addition from those produced by fiber drawing; and (iii) to interpret the changes in the matrix molecular mobility (produced by silica and/or drawing). Scanning electron microscopy (SEM) evidenced a good dispersion of nanoparticles at fractions up to 0.5 vol % of the nanofiller. X-ray diffraction (XRD) analyses revealed the increase in crystallinity after drawing of both neat polypropylene (PP) and produced nanocomposite fibers. Consequently, tensile modulus and stress at break of the fibers were enhanced. Drawn fibers containing 0.25⁻0.5 vol % of nanofiller showed also a remarkable increase in the creep resistance. Loss modulus of drawn fibers showed a pronounced α-relaxation peak at about 65 °C; the higher the draw ratio, the higher the peak intensity. Thermal and mechanical properties of composite fibers were improved due to the combined effects of nanofiller reinforcement and fiber orientation produced during hot drawing. Both fumed silica and draw ratio were significantly effective on tensile modulus and tenacity of nanocomposite fibers up to 0.5 vol % of AR974.


Complications of infection with Epstein-Barr virus during childhood: a study of children admitted to the hospital.
We undertook a study of infection with Epstein-Barr virus (EBV) in order to ascertain the spectrum of complications from this disease. During a 6-year period, 51 children were admitted; review of the 50 available records confirmed the diagnosis of EBV infection in 48, 37 of whom had clinical infectious mononucleosis. The indications for admission were diagnostic evaluation in 14 (29%) children, airway obstruction in 12 (25%) children, dysphagia and dehydration in 11 (23%) children, airway obstruction and dehydration in 2 (4%) children, severe malaise in 2 (4%) children, pneumonia in 2 (4%) children, encephalitis in 2 (4%) children, Guillain-Barré syndrome in 1 (2%) child and unrelated conditions in 2 (4%) children. Additional complications developing during hospitalization included peritonsillar abscess, pancytopenia, pleural effusion, hepatitis and hyponatremia. We believe that infection with EBV has a higher morbidity in childhood than previously appreciated.


Effects of alpha-Hydroxy-2-Pyridinemethanesulfonic Acid on Photosynthetic Carbon Dioxide Uptake and Stomatal Movements in Excised Tomato Leaves.
The effects of 10(-2)m alpha-hydroxy-2-pyridinemethanesulfonic acid (alphaHPMS) on the CO(2) compensation point, photosynthetic CO(2) uptake, CO(2) evolution into CO(2)-free air in light, and stomatal movement, in excised tomato leaves (Lycopersicon esculentum Mill. Eurocross BB-F(1) Hybrid) were studied. It was found that alpha-HPMS had a transient lowering effect on the CO(2) compensation point of treated leaves within the first 5 minutes of application. The net photosynthetic CO(2) uptake was inhibited by alpha-HPMS treatment. The inhibition increased with time and was enhanced in an O(2)-free atmosphere. The CO(2) evolution into CO(2)-free air in light was inhibited by alpha-HPMS. The inhibition was O(2)-dependent because the effect was observed only in 21% O(2) but not in O(2)-free N(2). Stomatal apertures were affected by alpha-HPMS, but the effect was transient and was observed 15 to 30 minutes after the application. The time course of this closure did not account for the observed inhibition of net CO(2) uptake.


Intraperitoneal Pressure in Polycystic and Non-Polycystic Kidney Disease Patients, Treated by Peritoneal Dialysis.
Intraperitoneal volume (IPV) should be individualized and aimed to maintain an intraperitoneal pressure (IPP) lower than 17 cm H2O. IPP is very variable, given its relation with body size. However, it is not yet fully understood which anthropometric variable mostly affects IPP and the relation between IPP and organomegaly in polycystic kidney disease (PKD) patients is not known. The aim of the present study was to analyse the relation between antropometric variables and IPP in a large cohort of peritoneal dialysis (PD) patients and to identify if a relation between nephromegaly and IPP exists in PKD patients. IPP was measured in PD patients and data was retrospectively collected. In PKD patients, total kidney volumes were measured in CT scans, and normalized with height (hTKV). Seventy-seven patients were included in the study, 18% affected by PKD. Mean IPP was 14.9 ± 2.9 cm H2O and it showed significant positive correlation with body mass index (BMI; ρ = 0.42, p < 0.001). No correlation was found between IPP and absolute IPV; conversely, IPP has a significant inverse correlation with IPV normalized with BMI and body surface area (ρ -0.38, p = 0.001 and ρ -0.25, p = 0.02, -respectively). Patients with IPP >17 cm H2O have significant larger BMI and lower IPV/BMI compared to those with IPP <17 cm H2O (29 ± 3.6 vs. 26 ± 4 kg/m2, p < 0.05 and 97 ± 15.5 vs. 109 ± 22 mL/kg/m2, p < 0.05). PKD patients have a wide variability in hTKV (range 645-3,787 mL/m2) and it showed a significant correlation with IPP/IPV (ρ = 0.6, p < 0.05). Patients with larger BMI have greater IPP, irrespectively to IPV. In PKD patients, hTKV correlate with IPP/IPV ratio. However, given the wide range of distribution of hTKV, increased IPP cannot be presumed because of pre-existing polycystic kidney, but need to be quantified.


Do the issues of religious minority and coastal climate crisis increase the burden of chronic illness in Bangladesh?
Chronic illness with disability and its out-of-pocket expenditure (OOPE) remains a big financial challenge in Bangladesh. The purpose of this study was to explore how religious minority problem and coastal climate crisis with other common risk factors determined chronic illness with a disability and its financial burden in Bangladesh. Existing policy responses, especially, social safety net programs and their governance were analyzed for suggesting better policy options that avoid distress financing. Binary logistic and multiple linear regression models were respectively used to identify the factors of disability, and high OOPE based on Bangladesh Household Income and Expenditure Survey 2016 data. We found that disable people had relatively higher OOPE than their non-disabled counterparts and this OOPE further surges when the number of disabilities increases. In addition to the common factors, the novelty of our findings indicated that the religious minority problem as well as the coastal climate crisis have bearing on the disability burden in Bangladesh. The likelihood of having a chronic illness with a disability was 13.2% higher for the religious minorities compared to the majorities (Odds ratio (OR): 1.132, 95% confidence interval (CI): 1.033-1.241) and it was 21.6% higher for the people who lived in the exposed coast than those who lived in the non-exposed area (OR: 1.216, 95% CI: 1.107-1.335). With disabilities, people from the exposed coast incurred higher OOPE than those from the non-exposed areas. Although receiving assistance from social safety net programs (SSNPs) seemed to reduce their high OOPE and financial distress such as selling assets and being indebted, the distribution was not equitably and efficiently managed to confirm the process of inclusion leakage-free. On average, those who enrolled from the minority group and the exposed coast paid the relatively higher bribes. To reduce burden, the government should strengthen and specify the existing SSNPs more for disable people, especially from the minority group and the exposed coast, and ensure the selection process more inclusive and leakage-free.


Molecular evolution of the hepatitis B virus genome.
The hepatitis B virus (HBV) has a circular DNA genome of about 3,200 base pairs. Economical use of the genome with overlapping reading frames may have led to severe constraints on nucleotide substitutions along the genome and to highly variable rates of substitution among nucleotide sites. Nucleotide sequences from 13 complete HBV genomes were compared to examine such variability of substitution rates among sites and to examine the phylogenetic relationships among the HBV variants. The maximum likelihood method was employed to fit models of DNA sequence evolution that can account for the complexity of the pattern of nucleotide substitution. Comparison of the models suggests that the rates of substitution are different in different genes and codon positions; for example, the third codon position changes at a rate over ten times higher than the second position. Furthermore, substantial variation of substitution rates was detected even after the effects of genes and codon positions were corrected; that is, rates are different at different sites of the same gene or at the same codon position. Such rates after the correction were also found to be positively correlated at adjacent sites, which indicated the existence of conserved and variable domains in the proteins encoded by the viral genome. A multiparameter model validates the earlier finding that the variation in nucleotide conservation is not random around the HBV genome. The test for the existence of a molecular clock suggests that substitution rates are more or less constant among lineages. The phylogenetic relationships among the viral variants were examined. Although the data do not seem to contain sufficient information to resolve the details of the phylogeny, it appears quite certain that the serotypes of the viral variants do not reflect their genetic relatedness.


Experimental and theoretical study of quasicoherent fluctuations in enhanced D(alpha) plasmas in the Alcator C-Mod tokamak.
A comparison of experimental measurements and theoretical studies of the quasicoherent (QC) mode, observed at high densities during enhanced D(alpha) (EDA) H mode in the Alcator C-Mod tokamak, are reported. The QC mode is a high frequency ( approximately 100 kHz) nearly sinusoidal fluctuation in density and magnetic field, localized in the steep density gradient ("pedestal") at the plasma edge, with typical wave numbers k(R) approximately 3-6 cm(-1), k(theta) approximately 1.3 cm(-1) (midplane). It is proposed here that the QC mode is a form of resistive ballooning mode known as the resistive X-point mode, in reasonable agreement with predictions by the BOUT (boundary-plasma turbulence) code.


Tough, Transparent, 3D-Printable, and Self-Healing Poly(ethylene glycol)-Gel (PEGgel).
Polymer gels, such as hydrogels, have been widely used in biomedical applications, flexible electronics, and soft machines. Polymer network design and its contribution to the performance of gels has been extensively studied. In this study, the critical influence of the solvent nature on the mechanical properties and performance of soft polymer gels is demonstrated. A polymer gel platform based on poly(ethylene glycol) (PEG) as solvent is reported (PEGgel). Compared to the corresponding hydrogel or ethylene glycol gel, the PEGgel with physically cross-linked poly(hydroxyethyl methacrylate-co-acrylic acid) demonstrates high stretchability and toughness, rapid self-healing, and long-term stability. Depending on the molecular weight and fraction of PEG, the tensile strength of the PEGgels varies from 0.22 to 41.3 MPa, fracture strain from 12% to 4336%, modulus from 0.08 to 352 MPa, and toughness from 2.89 to 56.23 MJ m-3 . Finally, rapid self-healing of the PEGgel is demonstrated and a self-healing pneumatic actuator is fabricated by 3D-printing. The enhanced mechanical properties of the PEGgel system may be extended to other polymer networks (both chemically and physically cross-linked). Such a simple 3D-printable, self-healing, and tough soft material holds promise for broad applications in wearable electronics, soft actuators and robotics.


Changing Therapeutic Paradigms: Predicting mCRC Lesion Response to Selective Internal Radionuclide Therapy (SIRT) based on Critical Absorbed Dose Thresholds: A Case Study.
A 65 year old male with metastatic colorectal cancer (mCRC) in the liver was referred for selective internal radionuclide therapy (SIRT) following a history of extensive systemic chemotherapy. 90Y PET imaging was performed immediately after treatment and used to confirm lesion targeting and measure individual lesion absorbed doses. Lesion dosimetry was highly predictive of eventual response in the follow-up FDG PET performed 8 weeks after therapy. The derived radiation dose map was used to plan a second SIRT procedure aiming to protect healthy liver by keeping absorbed dose below the critical dose threshold, whilst targeting the remaining lesions that had received sub-critical dosing. Again, 90Y PET was performed immediately post-treatment and used to derive absorbed dose measures to both lesions and healthy parenchyma. Additional follow-up FDG PET imaging again confirmed the role of the 90Y PET dose map as an early predictor of response, and a tool for safe repeat treatment planning.


[Diffusion of vancomycin in the cerebrospinal fluid, in the dog, in the absence of meningeal inflammation].
The diffusion of vancomycin into the cerebro-spinal fluid was studied in 5 healthy dogs. Its appears that vancomycin does diffuse across the blood-brain barrier. Though the concentrations reached in the CSF are low, they are of the same order of magnitude as the minimal inhibitory concentrations of this antibiotic towards the germs usually treated. The usual pharmacokinetic parameters were determined.


Radical prostatectomy or radiotherapy reduce prostate cancer mortality in elderly patients: a population-based propensity score adjusted analysis.
Contemporary data regarding the effect of local treatment (LT) vs. non-local treatment (NLT) on cancer-specific mortality (CSM) in elderly men with localized prostate cancer (PCa) are lacking. Hence, we evaluated CSM rates in a large population-based cohort of men with cT1-T2 PCa according to treatment type. Within the SEER database (2004-2014), we identified 44,381 men ≥ 75 years with cT1-T2 PCa. Radical prostatectomy and radiotherapy patients were matched and the resulting cohort (LT) was subsequently matched with NLT patients. Cumulative incidence and competing risks regression (CRR) tested CSM according to treatment type. Analyses were repeated after Gleason grade group (GGG) stratification: I (3 + 3), II (3 + 4), III (4 + 3), IV (8), and V (9-10). Overall, 4715 (50.0%) and 4715 (50.0%) men, respectively, underwent NLT and LT. Five and 7-year CSM rates for, respectively, NLT vs. LT patients were 3.0 and 5.4% vs. 1.5 and 2.1% for GGG II, 4.5 and 7.2% vs. 2.5 and 2.8% for GGG III, 7.1 and 10.0% vs. 3.5 and 5.1% for GGG IV, and 20.0 and 26.5% vs. 5.4 and 9.3% for GGG V patients. Separate multivariable CRR also showed higher CSM rates in NLT patients with GGG II [hazard ratio (HR) 3.3], GGG III (HR 2.6), GGG IV (HR 2.4) and GGG V (HR 2.6), but not in GGG I patients (p = 0.5). Despite advanced age, LT provides clinically meaningful and statistically significant benefit relative to NLT. Such benefit was exclusively applied to GGG II to V but not to GGG I patients.


Fossil coleoid cephalopod from the Mississippian Bear Gulch Lagerstätte sheds light on early vampyropod evolution.
We describe an exceptionally well-preserved vampyropod, Syllipsimopodi bideni gen. et sp. nov., from the Carboniferous (Mississippian) Bear Gulch Lagerstätte of Montana, USA. The specimen possesses a gladius and ten robust arms bearing biserial rows of suckers; it is the only known vampyropod to retain the ancestral ten-arm condition. Syllipsimopodi is the oldest definitive vampyropod and crown coleoid, pushing back the fossil record of this group by ~81.9 million years, corroborating molecular clock estimates. Using a Bayesian tip-dated phylogeny of fossil neocoleoid cephalopods, we demonstrate that Syllipsimopodi is the earliest-diverging known vampyropod. This strongly challenges the common hypothesis that vampyropods descended from a Triassic phragmoteuthid belemnoid. As early as the Mississippian, vampyropods were evidently characterized by the loss of the chambered phragmocone and primordial rostrum-traits retained in belemnoids and many extant decabrachians. A pair of arms may have been elongated, which when combined with the long gladius and terminal fins, indicates that the morphology of the earliest vampyropods superficially resembled extant squids.


Independent and combined influence of physical fitness components on self-esteem in adolescents: DADOS study.
Self-esteem is a common indicator of psychological well-being, but its relationship with physical fitness components during adolescence is not fully understood. The aims of this study were to analyse the association of physical fitness components (low vs. high) with self-esteem in adolescents, and to examine the combined influence of physical fitness on self-esteem. A total of 225 participants (44% girls), aged 13.9 ± 0.3 years, from the DADOS (Deporte, ADOlescencia y Salud) study were included in the analyses. ALPHA-Fitness Test Battery was used to evaluate physical fitness components. The Spanish version of the Behaviour Assessment System for Children-3 questionnaire was used to assess self-esteem. Our results showed differences on self-esteem between groups of cardiorespiratory fitness (low = 49.51 ± 12.03 vs. high = 55.01 ± 4.46; p < 0.05) and upper limb muscular strength (low = 53.87 ± 7.38 vs. high = 54.29 ± 5.99; p < 0.05). Lower limb muscular strength and speed-agility groups did not show statistical differences. Significant differences on self-esteem were found when comparing adolescents with a physical fitness index of ≤1 vs. 4 (52.66 vs. 55.28; p < 0.05). These findings suggest that cardiorespiratory fitness and upper limb muscular strength are positively related with self-esteem. Moreover, our results revealed a combined influence of physical fitness on the self-esteem of adolescents.


[Reversal effect of nuclear factor-κB protease inhibitor PDTC on multidrug resistance of K562/AO₂ cells and its mechanism].
This study was purposed to investigate the relationship between activation of nuclear factor-κB (NF-κB) and multidrug resistance in K562/AO₂ cells and its mechanism. Human erythroleukemic cell line K562 and its adriamycin-resistant counterpart K562/AO₂ cells were used in the study. After inhibiting the activation of NF-κB with noncytotoxic concentration of antioxidant pyrrolidine dithiocarbamate (PDTC) in vitro, the multiple of drug resistance of K562/AO₂ cells was assessed by MTT assay. RT-PCR and flow cytometry method were used to detect the relative expression of mdr-1 mRNA and P-gp, respectively. The results showed that (1) multidrug resistance of K562/AO₂ cells to ADM was 59 times higher than that of K562 cells. When being pretreated with 0.2 μmol/L PDTC which is noncytotoxic to cells, the IC₅₀ of ADM in K562/AO₂ cells was sharply decreased with relative reverse efficiency of 93.03%, which was more higher than that of classic modifying agents Verapamil (Ver); (2) NF-κB activity of K562/AO₂ cells was significantly higher than that of K562 cells (p < 0.01). When being treated with PDTC, the activation of NF-κB was sharply decreased in K562/AO₂ cells; with 0.2 μmol/L PDTC for 24 hours it decreased to the lowest, nearly to the K562 cell level (p > 0.05); (3) the relative expression of both mdr-1 mRNA and P-gp in K562/AO₂ cells was more higher; the expressions of mdr-1 mRNA and P-gp both were inhibited in K562/AO₂ cell group treated with PDTC for 48 hours. It is concluded that the PDTC used as an inhibitor of NF-κB activity can partially reverse the multidrug resistance of K562/AO₂ cells, which mechanism can be associated with the down-regulation of mdr-1 mRNA and P-gp.


Increasing knowledge about the older population: the role of geriatric curriculum in optometry.
Education in the area of geriatrics/gerontology alleviates misconceptions about the elderly and lessens ageism. Ageism, negative feelings toward the elderly, represents a substantial obstacle to the delivery of quality health care to older adults. As future primary health care professionals, optometry students will encounter a large segment of the older population. This study looks at the effect that a didactic course and a clinical rotation in geriatrics have on the knowledge and attitude of optometry students toward older adults. Palmore's Facts on Aging Quiz: Part 1 was administered to two classes of optometry students. One class experienced a geriatric course and clinic concurrently; the other class experienced the geriatric clinic before the course. Scores increased significantly post-test for both classes. Exposure to geriatric patients before didactic instruction did not improve pretest scores; however, the number of patient exposures was significant at post-test. Antiage bias scores also improved with intervention of a didactic course and clinical rotation in geriatrics. The results of this study indicate that ageism in optometrists may be ameliorated by providing formal instruction in geriatrics in the optometric curriculum.


A novel species of cytochrome P-450 (P-450ib) specific for the small intestine of rabbits. cDNA cloning and its expression in COS cells.
We have isolated a cDNA clone for a P-450, designated P-450ib (Ichihara, K., Kusunose, E., Kaku, M., Yamamoto, S., and Kusunose, M. (1985) Biochim. Biophys. Acta 831, 99-105), from a cDNA library of rabbit small intestine mucosa by using synthetic DNA fragment by the polymerase chain reaction, as a hybridization probe. The cDNA with a 1,829-base pair insert encodes a polypeptide of 501 amino acids. The deduced amino acid sequence contains all of the sequences of the NH2-terminal and 14 tryptic fragments from purified P-450ib. As the NH2-terminal methionine was not found in the sequence from the purified protein, the apoprotein of P-450ib is composed of 500 amino acids with a molecular weight of 57,193. P-450ib shows 35-41% sequence similarity with several members of 8 subfamilies in the P-450 II family, whereas it has a less than 30% sequence similarity with other P-450 families, suggesting that this P-450 is the first member of a novel subfamily within the P-450 II family. RNA blot analysis shows that mRNA hybridized to the cDNA is expressed in the small intestine, but not significantly in other tissues including liver, colon, kidney, lung, spleen, brain, stomach, and cecum, indicating that P-450ib is a P-450 specific to the small intestine. The protein expressed in COS-7 cells using the cDNA in an expression vector, pKCRH2, shows benzphetamine N-demethylase activity and gives a band identical with that of P-450ib in its mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis.


Reliability and validation of the joint dysfunction index as a new assessment instrument for therapeutic efficacy for Kashin-Beck disease.
The objective of this study was to evaluate the reliability and validity of the joint dysfunction index (JDI) for assessment of therapeutic efficacy for Kashin-Beck disease (KBD). In an initial survey, completed questionnaires were obtained from 276 of 281 patients (98.2 %). A follow-up survey was completed with 64 KBD patients among 276 cases. A third survey selected 60 KBD patients who underwent intra-articular injection of sodium hyaluronate in the knees ascertained from the findings of the second questionnaire. Reliability was assessed using test-retest, "split-half" reliability and Cronbach's alpha coefficient. Factor analysis and item-to-domain correlation were used to analyze validity. The coefficient of variation (CV) was used to measure the sensitivity of scale. Feasibility assessment included consideration of completion time, rate of recovery, and time of completion. Reliability analysis comprised a test-retest correlation coefficient of 0.404-0.546 and a kappa test of 0.404-0.546. Internal consistency analysis comprised a Cronbach alpha coefficient of 0.689 and a split-half coefficient of 0.677. Principal component factor analysis for validity testing extracted a common factor with a cumulative variance contribution of 45.44 %. The JDI score from 276 KBD cases revealed no significant difference associated with age, gender, education, or the body mass index. Sensitivity analysis showed that there was no significant difference between pre-treatment and post-treatment values, with a CV of 96.55-172.06 %. In conclusion, the JDI can be used to evaluate the efficacy of agents used to treat KBD.


Relationships of obesity indices to serum insulin and lipoproteins in relatives of black patients with noninsulin-dependent diabetes mellitus (NIDDM).
We have examined the relationships between obesity indices and various metabolic parameters in seven obese (body mass index (BMI) mean +/- s.e.m. 42 +/- 2.5 kg/m2), ten nonobese (BMI 25.3 +/- 1.2 kg/m2) nondiabetic female relatives of black patients with NIDDM and eight healthy controls (BMI 24.5 +/- 1.1 kg/m2). Despite the greater BMI in the obese relatives, percent body fat was not different from that of the nonobese relatives (38 +/- 2 vs 34 +/- 3 percent). Both values were, however, significantly (P less than 0.05) greater than that of the healthy controls (25 +/- 3 percent). Mean waist-to-hip circumference ratio (WHR) was greatest in obese relatives (0.89 +/- 0.01), intermediate in nonobese relatives (0.83 +/- 0.01) and least in the healthy controls (0.77 +/- 0.04). Mean sum of skinfold thickness from biceps, triceps and subscapular (SS) region was also greatest in obese relatives, intermediate in nonobese relatives and least in controls. Centrality index was not, however, different among the groups. Mean fasting serum glucose levels were slightly higher but not significantly different in the relatives compared to controls (obese 82 +/- 3; nonobese 81 +/- 4; controls 75 +/- 3 mg/dl). Following oral glucose ingestion, serum glucose rose to significantly (P less than 0.05) greater levels at 30, 60 and 90 min in the relative subgroups vs controls. Mean fasting and post-prandial peak serum insulin concentrations were significantly (P less than 0.05-0.01) greater in both relative subgroups vs controls. While mean serum glucose profiles and glucose disappearance decay (KG) following intravenous glucose load were identical in the relatives and controls, serum insulin responses were significantly greater in the relatives. The mean basal and post-stimulation serum C-peptide concentrations were similar in all the three groups, irrespective of the stimulus; thus suggesting a reduced hepatic insulin extraction in the relatives. Fasting serum cholesterol, triglyceride, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) as well as FFA levels were not different between the relatives and controls despite the hyperinsulinemia in the former group. WHR correlated with basal insulin in the relatives (r = 0.416, P less than 0.05) and controls (r = 0.68, P less than 0.01) but not with stimulated insulin, lipids and lipoproteins in any of the groups. In contrast, both percent BFM and SS thickness correlated significantly (P less than 0.001) with post-glucose insulin concentrations in the relatives only.(ABSTRACT TRUNCATED AT 400 WORDS)


Experimental study in vivo ablation of swine pancreas using high-intensity focused ultrasound.
The objective of this study is to evaluate the feasibility and safety of high-intensity focused ultrasound (HIFU) for ablation of swine pancreas and to detect the pathological variations in pancreas damage. (a) Eight swine were involved and randomly divided into two groups (Group A and B). HIFU was applied on swine in both groups for in vivo ablation of pancreas. The animals were anesthetized, and the artificial acoustic window was built. Then, the irradiation of FEP-BY02 type HIFU on pancreas was applied. (b) Swine in Group A were euthanized immediately after treating with HIFU to examine variations in pancreas. The biochemical evidence of pancreatitis was evaluated by blood samples collected from swine in Group B before and after HIFU. Then, the pancreas of swine in Group B was euthanized on day 5 after treatment to examine the pancreas. All specimens were visually inspected for both ultrasonic focal damage region (UFDR) and pathological routine by a skilled pathologist. (a) The vital signs of all animals were stable during HIFU treatment and recovered well after treatment. (b) UFDR were observed in all HIFU irradiation region of the specimens, without significant size difference between the two groups. The coagulation nucleus pyknosis, cytochylema vacuolation, and nucleus membrane disruption were observed after HIFU in both groups. Membranous structure dissolution and inflammatory cell infiltration were also found after HIFU in swine of Group B. (c) There was no significant difference in the levels of blood amylase in swine of Group B before and after HIFU treatment. It was feasible and safe to use HIFU for ablation of the pancreas in swine.


[Study on the correlation between membrane protein Flotillin-1 and PrPc endocytosis].
To explore whether the membrane-associated protein Flotillin-1 has relationship with endocytosis of PrPc. The expression of Flotillin-1 in different cell lines was detected with the method of Western Blot; the interaction between Flotillin-1 and PrPc in Cells which were treated with copper ions was observed using immunoprecipitation method. (1) Flotillin-1 was widely expressed in many cell lines without significant difference in the amounts of expression level; (2) Only in the appearance of copper ions, the protein complexes of PrPc and Flotillin-1 can be detected with the method of IP, which were related to copper ions concentration and processing time. The membrane-associated protein Flotillin-1 has the relationship with the endocytosis of PrPc.


Congenital hypothyroidism in a Turkish family: the role of immunoglobulins blocking the trophic effects of TSH and maternal-foetal relationship.
A Turkish family with frequent intermarriages is described, in which two siblings were born with persistent forms of congenital hypothyroidism, in the elder child concomitant with absent radioactive thyroid imaging. The mother was clinically euthyroid throughout the period of observation, but showed in addition to thyroid microsomal antibodies, high levels of immunoglobulins blocking the trophic action of TSH. These maternal growth blocking antibodies were transiently present in the youngest of the siblings (from birth to 2 months of age). She had a relatively mild form of congenital hypothyroidism (T3: 33 micrograms/100 ml; T4: 3.9 micrograms/100 ml). The older sibling, with proven non-functioning thyroid tissue (negative thyroidscan, T4: 0.4 microgram/100 ml) produced the growth-blocking immunoglobulins herself and may thus represent a juvenile form of thyroid autoimmunity with a very early onset. An aunt and uncle of the children, both hypothyroid since birth, were at the age of 19 and 18 years weakly positive for growth blocking immunoglobulins. This study indicates that familial forms of congenital hypothyroidism are probably complex and may be brought about by maternal to foetal passage of thyroid reactive autoantibodies, but also by the inheritance of a trait for thyroid autoimmunity. In some cases these two mechanisms might act in conjunction.


Composite Nitride Nanoceramics in the System Titanium Nitride (TiN)-Aluminum Nitride (AlN) through High Pressure and High Temperature Sintering of Synthesis-Mixed Nanocrystalline Powders.
Presented is a study on the original preparation of individual and in situ intimately mixed composite nanocrystalline powders in the titanium nitride-aluminum nitride system, Ti:Al = 1:1 (at.), which were used in high pressure (7.7 GPa) and high temperature (650 and 1200 °C) sintering with no binding additives for diverse individual and composite nanoceramics. First, variations in precursor processing pathways and final nitridation temperatures, 800 and 1100 °C, afforded a pool of mixed in the nanosized regime cubic TiN (c-TiN) and hexagonal AlN (h-AlN) composite nanopowders both with varying average crystallite sizes. Second, the sintering temperatures were selected either to preserve initial powder nanocrystallinity (650 °C was lower than both nitridation temperatures) or promote crystal growth and recrystallization (1200 °C was higher than both nitridation temperatures). Potential equilibration towards bimetallic compounds upon solution mixing of the organometallic precursors to nanopowders, monomeric Ti[N(CH3)2]4 and dimeric {Al[N(CH3)2]3}2, was studied with 1H and 13C NMR in C6D6 solution. The powders and nanoceramics, both of the composites and individual nitrides, were characterized if applicable by powder XRD, FT-IR, SEM/EDX, Vicker's hardness, and helium density. The Vicker's hardness tests confirmed many of the composite and individual nanoceramics having high hardnesses comparable with those of the reference h-AlN and c-TiN ceramics. This is despite extended phase segregation and, frequently, closed microsized pore formation linked mainly to the AlN component. No evidence was found for metastable alloying of the two crystallographically different nitrides under the applied synthesis and sintering conditions. The high pressure and high temperature sintering of the individual and in situ synthesis-mixed composite nanopowders of TiN-AlN was demonstrated to yield robust nanoceramics.


Lovastatin-associated rhabdomyolysis.
Lovastatin is a new drug that has become popular for the treatment of patients with hyperlipidemias. Rhabdomyolysis is a well-documented and potentially dangerous side effect of lovastatin therapy. Critical care nurses should be aware of the symptoms and treatment of rhabdomyolysis. Patients receiving lovastatin should be instructed to report muscle pain or weakness and dark urine immediately. It should be determined whether patients are at risk for development of rhabdomyolysis from other causes so that lovastatin can be withheld. Early diagnosis and treatment can prevent serious complications in patients with lovastatin-induced rhabdomyolysis.


Effect of phenolic structures on the degradability of cell walls isolated from newly extended apical internode of tall fescue (Festuca arundinacea Schreb.).
Apical internodes of tall fescue (Festuca arundinacea Schreb. var. Clarine) harvested at flowering were sectioned into 5 or 10 equal parts to study in situ degradability and cell wall composition, respectively. The basal (youngest) section had the greatest primary wall content. Cell walls in the upper (older) sections had the highest xylose/arabinose ratio and lignin content and a lignin rich in syringyl units, all typical of extensive secondary wall development. Almost all of the p-coumaric (p-CA) and about half of the ferulic acid (FA) were released by 1 M NaOH and presumed to be ester-linked. The total FA content was approximately double that of p-CA in all sections other than the youngest with a distribution similar to that of total p-CA. However, the ratio of esterified to ether and ether plus ester linked (Et & Et+Es) FA differed with age. Whereas the esterified form remained essentially constant ( approximately 4.5 g/kg of cell wall), Et & Et+Es ferulate increased with increasing age of the tissue and was significantly related to lignin deposition (r = 0.79, P < 0.01). The extent of cell wall degradation after 48 h of incubation in the rumen was inversely related to maturity, falling from 835 g/kg of dry matter in the youngest section to 396 g/kg in the oldest. Both the rate and extent of cell wall degradation were significantly negatively related to the ratio of xylose to arabinose, lignin content, proportion of syringyl units present in lignin, and concentration of Et & Et+Es FA present. A positive relationship between Et & Et+Es FA was also found, with the rate (P < 0.01) being better correlated than the extent (P < 0.05) of cell wall degradation. Application of the newly extended internode model to fescue produced results consistent with the view that both the lignin content and the extent to which lignin was covalently bound to the other wall polymers crucially influenced the rate and extent of degradation.


Calcium Score Predicts Mortality After Revascularization in Critical Limb Ischemia.
The calcium score is a measure of vessel wall calcification and has clinical applications when studied in different vascular beds. The presence of vascular calcification in the arteries of the lower limbs is very common in patients with peripheral arterial disease; however, its relationship with the postoperative outcomes in patients undergoing lower limb revascularization is still poorly studied. The aim of this study is to evaluate association between the calcium score of lower limbs and the postoperative outcomes in patients with peripheral arterial disease undergoing revascularization procedures. We retrospectively analyzed 88 lower limb revascularization procedures in 72 patients with critical limb ischemia who had enhanced computed tomography for preoperative evaluation. The calcium score was calculated, from the angiographic phase of preoperative computed tomography, in the segments of the aorta, iliac, femoropopliteal, and infrapopliteal. It was also calculated the calcium score of the operated limb, and the total calcium score using a standardized method. The outcomes evaluated were the occurrence of acute myocardial infarction, amputation, patency, technical success, and death from any cause. Patients were followed up through a 12 month period. Among the 88 procedures performed, 31 (43.1%) lesions were classified as Trans-Atlantic Inter-Society Consensus Document II D. There were 66 (75%) endovascular procedures, 16 (18.2%) open surgery, and 6 (6.8%) hybrid interventions. No statistically significant relationship was found between the calcium score of the segments (aorta, iliac, femoropopliteal, infrapopliteal, the operated limb, and total calcium score) and the outcomes of acute myocardial infarction, amputation, patency, and technical success in any of the periods analyzed. The calcium score of the operated limb was higher in patients who died within 30 days and 6 months (6571 vs 2590.6; p=0.026) and (5227.8 vs 2335.3; p=0.036). A standardized calcium score calculation method with the angiographic phase of the computed tomography is feasible and reproducible. Higher values of the calcifications of the operated limb are related to a greater chance of death in the postoperative period. The calcium score of the operated limb can be considered as a marker of clinical severity and prognosis in this group of patients.


Modification of therapy from insulin to chlorpropamide decreases HDL cholesterol in patients with non-insulin-dependent diabetes mellitus.
In 27 patients with non-insulin-dependent diabetes mellitus, we determined fasting serum glucose, hemoglobin A1, body weight, serum triglycerides, cholesterol, low-density lipoprotein cholesterol (LDL-chol), high-density lipoprotein cholesterol (HDL-chol), and very-low-density lipoprotein cholesterol during treatment with insulin and several months after changing treatment to chlorpropamide. In five patients, diabetic control deteriorated to the point where insulin was reinitiated. In the remaining 22 patients, despite a significant decrease in weight (122 +/- 5 vs. 114 +/- 5% ideal body wt; P less than .025) on chlorpropamide, HDL-chol fell from 49 +/- 4 to 40 +/- 4 mg/dl (P less than .01) when therapy was modified from insulin to the sulfonylurea. There was a concomitant increase in LDL-chol:HDL-chol from 3.6 +/- 0.3 to 4.4 +/- 0.5 (P less than .05). In the 5 patients in whom insulin was reinstituted, HDL-chol increased to its previous level on insulin (P less than .05). Changing antidiabetic medication from insulin to sulfonylureas may alter the lipoproteins in a manner that increases cardiovascular risk.


[Botulinum toxin therapy in rehabilitation neurology].
Intramuscular injections of botulinum toxin (BT) induce a localized, long-lasting paresis of the target muscle that can be graded by the BT dose administered and that is free of major side effects. With this profile, BT can be used for symptomatic treatment of various disorders caused by pathological muscle hyperactivities. These disorders occur frequently in patients in institutions for neurological rehabilitation. They are difficult to treat with conventional methods, can cause major suffering and induce substantial costs for our health care system. In the present study we therefore sought to delineate the use of BT in rehabilitative neurology. Regardless of the etiology of the particular muscle hyperactivity syndrome, five main indication groups are identified: (1) improvement of function of the hyperactive muscles; (2) relief of pain in the hyperactive muscles; (3) improvement of patient care; (4) avoidance of sequelae in joints, tendons, ligaments, and teeth; (5) various special indications.


Immunohistochemical demonstration of c-Kit-negative fibroblast-like cells in murine gastrointestinal musculature.
In the gastrointestinal musculature, interstitial cells of Cajal (ICC) distribute and regulate the gastrointestinal motility. Another type of mesenchymal cell, known as the fibroblast-like cell (FLC), has also been reported to be juxtaposed to the ICC. In this study, we examined the immunohistochemical properties of FLC in the murine gastrointestinal musculature using antibodies to small conductance Ca(2+)-activated K(+) channel 3 (SK3), platelet-derived growth factor receptor alpha (PDGFRalpha), and CD34. SK3-immunopositive (SK3-ip) cells were observed in the musculature throughout the gastrointestinal tract. These SK3-ip cells were distinct from the ICC that were identified by c-Kit immunoreactivity. In the muscular layers, SK3-ip cells were bipolar in shape and were associated with the intramuscular ICC and nerve fiber bundles. In the myenteric layer multipolar-shaped SK3-ip cells encompassed the myenteric ganglia. SK3-ip cells in the subserosal plane formed a cellular network with their ramified processes. The distribution pattern of the SK3-ip cells in the ICC-deficient W(v)/W(v) mutant mice was similar to that in normal mice. We also demonstrated that SK3-ip cells showed the intense PDGFRalpha immunoreactivity that was previously examined in FLC. However, CD34 immunoreactivity, one of the markers of human FLC, was not observed in SK3-ip cells with the exception of subserosal FLC. Thus, our observations indicate that SK3- and PDGFRalpha-double immunopositive cells are FLC in the murine gastrointestinal musculature and behave as a basic cellular element throughout the gastrointestinal musculature.


Structural Disruption of an Adenosine-Binding DNA Aptamer on Graphene: Implications for Aptasensor Design.
We report on the predicted structural disruption of an adenosine-binding DNA aptamer adsorbed via noncovalent interactions on aqueous graphene. The use of surface-adsorbed biorecognition elements on device substrates is needed for integration in nanofluidic sensing platforms. Upon analyte binding, the conformational change in the adsorbed aptamer may perturb the surface properties, which is essential for the signal generation mechanism in the sensor. However, at present, these graphene-adsorbed aptamer structure(s) are unknown, and are challenging to experimentally elucidate. Here we use molecular dynamics simulations to investigate the structure and analyte-binding properties of this aptamer, in the presence and absence of adenosine, both free in solution and adsorbed at the aqueous graphene interface. We predict this aptamer to support a variety of stable binding modes, with direct base-graphene contact arising from regions located in the terminal bases, the centrally located binding pockets, and the distal loop region. Considerable retention of the in-solution aptamer structure in the adsorbed state indicates that strong intra-aptamer interactions compete with the graphene-aptamer interactions. However, in some adsorbed configurations the analyte adenosines detach from the binding pockets, facilitated by strong adenosine-graphene interactions.


Deducing molecular similarity using Voronoi binding sites.
We have devised a new measure of molecular similarity with respect to given simple partitions of space into regions. The similarity is determined by numerical integration of the difference in the optimal interaction between the two molecules and the regions over a large range of interaction parameter values. Compounds differing in empirical formula are differentiated by a single infinite region; cis/trans or ortho/meta/para isomers are distinguishable by two adjacent regions that are half-spaces; and stereoisomers require five regions. This can be viewed as a natural classification of isomers. The concept can also be applied to drug binding studies to determine which molecules may bind alike in a given biological receptor and to elucidate a necessary starting geometry when a binding site is modeled for inhibitors whose experimental binding energies are different.


[An adult case of asymptomatic congenital tracheal stenosis].
We report an adult case of asymptomatic congenital tracheal stenosis. A 42-year-old woman was admitted to our hospital, whose chief complaint was tongue pain. Clinical examination revealed a tumor 35 x 20 mm in diameter along the middle, right edge of the tongue, and histopathological examination determined a diagnosis of squamous cell carcinoma of the tongue. She had no history of dyspnea, stridor nor recurrent pneumonia, and enjoyed playing table tennis in her daily life. Physical examination, electrocardiogram, spirogram and laboratory data showed no abnormal signs although chest roentgenogram revealed a narrowed trachea 6 mm in diameter, however, the tracheal stenosis was not noted at the time. On the 10th hospital day, radical operation for cancer of the tongue including right hemiglossectomy and supraomohyoid neck dissection, were performed. Oral intubation was not successful, and a tracheostomy was conducted. The trachea was incised, and revealed that complete tracheal rings existed without posterior membraneous tissue. The operation time was limited because of high airway pressure for a narrow tracheal tube (5 mm in diameter). The main postoperative complication was one crust formation in the tracheal lumen that resulted in CO2 narcosis due to check valve obstruction of the trachea on the 4th postoperative day. A nebulizer provided continuous moisture and was effective in preventing recurrence of the crust attachment to the tracheal membrane thus, the tracheostoma was closed by the 17th postoperative day. This case indicates that among healthy people there are extremely rare patients with congenital tracheal stenosis who survive their postnatal and infantile periods, and who experience no trouble in their daily lives. As physicians, we must be aware of this disease in adult patients in our clinics.


Development and Verification of a Combined Diagnostic Model for Sarcopenia with Random Forest and Artificial Neural Network.
Sarcopenia is a chronic disease characterized by an age-related decline in skeletal muscle mass and function, and diagnosis is challenging owing to the lack of a clear "gold standard" assessment method. This study is aimed at combining random forest (RF) and artificial neural network (ANN) methods to screen key potential biomarkers and establish an early sarcopenia diagnostic model. Three gene expression datasets were downloaded and merged by searching the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) in the merged dataset were identified by R software and subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Afterward, the STRING database was employed for interaction analysis of the differentially encoded proteins. Then, RF was used to identify key genes from the DEGs, and a sarcopenia diagnostic model was constructed by ANN. Finally, the diagnostic model was assessed using a validation dataset, while its diagnostic performance was evaluated by the area under curve (AUC) value. 107 sarcopenia-related DEGs were identified, and they were mainly enriched in the FoxO and AMPK signaling pathways involved in the molecular pathogenesis of sarcopenia. Thereafter, seven key genes (MT1X, FAM171A1, ZNF415, ARHGAP36, CISD1, ETNPPL, and WISP2) were identified by the RF classifier. The proteins encoded by three of these genes (CISD1, ETNPPL, and WISP2) may be potential biomarkers for sarcopenia. Finally, a diagnostic model for sarcopenia was successfully designed by ANN, achieving an AUC of 0.999 and 0.85 in the training and testing datasets, respectively. We identified several potential genetic biomarkers and successfully developed an early predictive model with high diagnostic performance for sarcopenia. Moreover, our results provide a valuable reference for the early diagnosis and screening of sarcopenia in the future.


DeepConsensus: Consensus-based Interpretable Deep Neural Networks with Application to Mortality Prediction.
Deep neural networks have achieved remarkable success in various challenging tasks. However, the black-box nature of such networks is not acceptable to critical applications, such as healthcare. In particular, the existence of adversarial examples and their overgeneralization to irrelevant, out-of-distribution inputs with high confidence makes it difficult, if not impossible, to explain decisions by such networks. In this paper, we analyze the underlying mechanism of generalization of deep neural networks and propose an (n, k) consensus algorithm which is insensitive to adversarial examples and can reliably reject out-of-distribution samples. Furthermore, the consensus algorithm is able to improve classification accuracy by using multiple trained deep neural networks. To handle the complexity of deep neural networks, we cluster linear approximations of individual models and identify highly correlated clusters among different models to capture feature importance robustly, resulting in improved interpretability. Motivated by the importance of building accurate and interpretable prediction models for healthcare, our experimental results on an ICU dataset show the effectiveness of our algorithm in enhancing both the prediction accuracy and the interpretability of deep neural network models on one-year patient mortality prediction. In particular, while the proposed method maintains similar interpretability as conventional shallow models such as logistic regression, it improves the prediction accuracy significantly.


A new method using a health index (HI) to screen low level toxic organic substances in consumer products.
To ensure selection of appropriate materials for industrial use in terms of toxicity, a procedure to estimate a health index (HI) that can be used for prioritizing less hazardous components of consumer products is described. The HI is based on the occupational exposure limits (OELs) of organic substances that compose the products. To calculate the HI of a product, it is often necessary to predict OEL values for the substances for which an OEL value has not yet been promulgated. We developed a method to estimate the OEL values from median lethal dose (LD50) data of rodent. A good correlation between known OEL values and the LD50 data was obtained by a multivariate regression analysis by introducing organic compensation coefficients, which were caluculated as 10 to the Bth power where B is the regression coefficient of dummy variables denoting the characteristics of the organic compounds such as functional groups, molecular structures, and so on. We believe that the use of the present method should be limited to predicting unknown OEL values for the HI and used for material prioritization. It should not be extended to determinations of regulatory OELs.


Heart failure non-invasive home telemonitoring systems: A systematic review.
Heart Failure (HF) is mostly a lifestyle-related disease that is suited to telemonitoring since patients' signs and symptoms can be assessed remotely by healthcare providers. Today, non-invasive telemonitoring programs are increasingly used in HF care to detect patients' deterioration. This study aims to review and assess the distinctive characteristics of the different telemonitoring systems (TMS) tested in HF patients through clinical trials (CTs). Discussing the impact of the evaluation results of these systems is also another objective of this work. The search for CTs studies related to non-invasive home TMS in HF patients has been made in Cochrane Library. Research works of interest were limited to those articles published between 2005 and March 2019. A total of 24 CTs that fully met the inclusion criteria were included in the final review. The main functionalities of these TMS were analyzed and compared among them. Also, the monitored parameters and significant findings of each trial were described. This review shows a wide difference among available functionalities deployed by the reviewed systems. Most of them did not take into account the recommendations of HF management specialists, detailed in the evidence-based Clinical Practice Guidelines (CPGs) of the most relevant cardiology associations. Due to this, there is a wide variety of TMS, which makes a comparison among them difficult. However, the few systems that comply with the CPGs recommendations found promising results, suggesting that the design of TMS for the HF management should take into account the recommendations of specialists (CPGs).


Computation-guided optimization of split protein systems.
Splitting bioactive proteins into conditionally reconstituting fragments is a powerful strategy for building tools to study and control biological systems. However, split proteins often exhibit a high propensity to reconstitute, even without the conditional trigger, limiting their utility. Current approaches for tuning reconstitution propensity are laborious, context-specific or often ineffective. Here, we report a computational design strategy grounded in fundamental protein biophysics to guide experimental evaluation of a sparse set of mutants to identify an optimal functional window. We hypothesized that testing a limited set of mutants would direct subsequent mutagenesis efforts by predicting desirable mutant combinations from a vast mutational landscape. This strategy varies the degree of interfacial destabilization while preserving stability and catalytic activity. We validate our method by solving two distinct split protein design challenges, generating both design and mechanistic insights. This new technology will streamline the generation and use of split protein systems for diverse applications.


Tenoxicam. An update of its pharmacology and therapeutic efficacy in rheumatic diseases.
Tenoxicam administered orally, rectally or parenterally is an effective analgesic and anti-inflammatory agent for the symptomatic treatment of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis and various rheumatic conditions such as tendinitis, bursitis, sciatica, back pain and gouty arthritis. In clinical trials its efficacy is at least equivalent to that of other NSAIDs and it is at least as well tolerated as piroxicam and probably better tolerated than diclofenac, indomethacin and ketoprofen. Compared with many other NSAIDs, tenoxicam offers certain advantages in that it is conveniently administered once daily and dosage adjustment is not required in the elderly or in patients with renal or hepatic impairment.


Genome-wide identification of a large repertoire of Ralstonia solanacearum type III effector proteins by a new functional screen.
The gram-negative plant-pathogenic bacterium Ralstonia solanacearum utilizes the hypersensitive response and pathogenicity (Hrp) type III secretion system (T3SS) to cause disease in plants. To determine the entire repertoire of effector proteins possessed by R. solanacearum RS1000, we constructed a transposon carrying a calmodulin-dependent adenylate cyclase reporter that can be used to specifically detect rip (Ralstonia protein injected into plant cells) genes by monitoring the cAMP level in plant leaves inoculated with insertion mutants. From the new functional screen using this transposon, we identified 38 new Rip proteins translocated into plant cells via the Hrp T3SS. In addition, most of the 34 known effectors of RS1000 could be detected by the screen, except for three effectors that appear to be small in size or only weakly expressed. Finally, we identified 72 Rips in RS1000, which include 68 effector proteins classified into over 50 families and four extracellular components of the Hrp T3SS. Interestingly, one-third of the effectors are specific to R. solanacearum. Many effector proteins contain various repeated amino acid sequences or known enzyme motifs. We also show that most of the R. solanacearum effector proteins, but not Hrp extracellular components, require an Hrp-associated protein, HpaB, for their effective translocation into plant cells.


Malpractice premiums and physicians' income: perceptions of a crisis conflict with empirical evidence.
The conventional wisdom is that malpractice premiums have steadily risen and now constitute a crisis for medical practice. The best available data suggest otherwise. American Medical Association (AMA) surveys of self-employed physicians from 1970 to 2000 indicate that premiums rose until 1986, then declined until 1996, rose thereafter, but were lower in 2000 than in 1986. Other items represented a much greater share of total practice expenses in 1970 yet increased rapidly until 1996 and moderately thereafter, while spending on premiums fell during 1986-2000. National trends were reflected with variations in obstetrics/gynecology, surgery, and anesthesiology and in nine regions surveyed.


Adolescent at-risk weight (overweight and obesity) prevalence in Hawai'i.
To present prevalence rates of adolescents in Hawai'i at-risk weight (85 percentile or higher = overweight or obese) and the relationship with comorbidities. The Hawai'i Youth Risk Behavior Survey aggregated for 2005, 2007, and 2009 was analyzed addressing at-risk weight prevalence by sex, race/ethnicity, and grade. Comorbidities were related to at-risk weight using regression. Over 1/4 of Hawai'i adolescents were at-risk weight. There were no differences by grade, but boys had higher prevalence (31.0%) than girls (22.4%). Overall, Other Pacific Islanders and Hawaiians had the highest prevalence (43.9% and 37.4%, respectively), followed by multi-race (27.1%), Filipino (25.7%), and Whites with the lowest (16.1%). Most associations between at-risk weight and various co-morbidities (including sexual behavior, nutrition, physical activity, mental health, bullying, alcohol, and other drug use) were not significant (p>.05). However, girls and boys trying to lose weight; and boys with 3+ hours of screen time (TV, video, or computer games) each day were at increased odds of at-risk weight (p<.05). Adolescent gender and ethnic disparities exist such that a single intervention approach (one size fits all) may be counterproductive. More research is required on the determinants and mechanisms to guide weight management interventions.


Supportive therapies for prevention of hepatocellular carcinoma recurrence and preservation of liver function.
Hepatocellular carcinoma (HCC) is one of the deadliest cancers in the world and is associated with a high risk of recurrence. The development of a wide range of new therapies is therefore essential. In this study, from the perspective of supportive therapy for the prevention of HCC recurrence and preservation of liver function in HCC patients, we surveyed a variety of different therapeutic agents. We show that branched chain amino acids (BCAA) supplementation and late evening snack with BCAA, strategies that address issues of protein-energy malnutrition, are important for liver cirrhotic patients with HCC. For chemoprevention of HCC recurrence, we show that viral control after radical treatment is important. We also reviewed the therapeutic potential of antiviral drugs, sorafenib, peretinoin, iron chelators. Sorafenib is a kinase inhibitor and a standard therapy in the treatment of advanced HCC. Peretinoin is a vitamin A-like molecule that targets the retinoid nuclear receptor to induce apoptosis and inhibit tumor growth in HCC cells. Iron chelators, such as deferoxamine and deferasirox, act to prevent cancer cell growth. These chelators may have potential as combination therapies in conjunction with peretinoin. Finally, we review the potential inhibitory effect of bone marrow cells on hepatocarcinogenesis.


[Correlation between estrogen receptor β and ABCC11 gene single nucleotide polymorphisms and axillary osmidrosis].
To explore the correlation between single nucleotide polymorphisms (SNPs) of hormone receptor gene or other related genes and axillary osmidrosis (AO). Methods: Whole blood samples of 219 patients with AO and 159 normal people were collected, and their genomic DNA was extracted. SNPs of 49 selected gene loci were detected and analyzed by using matrix-assisted laser analysis and ionization time of flight mass spectrometry and other related technologies. Results: There were significant differences in SNPs at rs1256061 of estrogen receptor β gene and rs17822931, rs16945916 and rs62058521 in ABCC11 gene between the AO patients and normal people (all P<0.01). 81.1% of patients with AO carried G allele at rs1256061, while only 63.2% of normal people carried G allele; 96.3% of patients with AO carried G allele at rs17822931, while only 4.4% of the normal people carried G allele; 28.6% of the patients with armpit odor carried the G allele of rs16945916, while only 0.6% of the normal people carried G allele; 28.0% of patients with AO carried G allele at rs62058521, while only 0.6% of the normal people carried G allele. Conclusion: SNPs of rs1256061 at the locus of estrogen receptor gene are correlated with the pathogenesis of AO, while SNPs at multiple loci (rs16945916, rs62058521 and rs17822931) in ABCC11 gene are correlated with the pathogenesis of AO.


Estimates of global SARS-CoV-2 infection exposure, infection morbidity, and infection mortality rates in 2020.
We aimed to estimate, albeit crudely and provisionally, national, regional, and global proportions of respective populations that have been infected with SARS-CoV-2 in the first year after the introduction of this virus into human circulation, and to assess infection morbidity and mortality rates, factoring both documented and undocumented infections. The estimates were generated by applying mathematical models to 159 countries and territories. The percentage of the world's population that has been infected as of 31 December 2020 was estimated at 12.56% (95% CI: 11.17-14.05%). It was lowest in the Western Pacific Region at 0.66% (95% CI: 0.59-0.75%) and highest in the Americas at 41.92% (95% CI: 37.95-46.09%). The global infection fatality rate was 10.73 (95% CI: 10.21-11.29) per 10,000 infections. Globally per 1000 infections, the infection acute-care bed hospitalization rate was 19.22 (95% CI: 18.73-19.51), the infection ICU bed hospitalization rate was 4.14 (95% CI: 4.10-4.18). If left unchecked with no vaccination and no other public health interventions, and assuming circulation of only wild-type variants and no variants of concern, the pandemic would eventually cause 8.18 million deaths (95% CI: 7.30-9.18), 163.67 million acute-care hospitalizations (95% CI: 148.12-179.51), and 33.01 million ICU hospitalizations (95% CI: 30.52-35.70), by the time the herd immunity threshold is reached at 60-70% infection exposure. The global population remained far below the herd immunity threshold by end of 2020. Global epidemiology reveals immense regional variation in infection exposure and morbidity and mortality rates.


Beneficial Activities of Alisma orientale Extract in a Western Diet-Induced Murine Non-Alcoholic Steatohepatitis and Related Fibrosis Model via Regulation of the Hepatic Adiponectin and Farnesoid X Receptor Pathways.
The hepatic adiponectin and farnesoid X receptor (FXR) signaling pathways play multiple roles in modulating lipid and glucose metabolism, reducing hepatic inflammation and fibrosis, and altering various metabolic targets for the management of non-alcoholic fatty liver disease (NAFLD). Alisma orientale (AO, Ze xie in Chinese and Taeksa in Korean) is an herbal plant whose tubers are enriched with triterpenoids, which have been reported to exhibit various bioactive properties associated with NAFLD. Here, the present study provides a preclinical evaluation of the biological functions and related signaling pathways of AO extract for the treatment of NAFLD in a Western diet (WD)-induced mouse model. The findings showed that AO extract significantly reversed serum markers (liver function, lipid profile, and glucose) and improved histological features in the liver sections of mice fed WD for 52 weeks. In addition, it also reduced hepatic expression of fibrogenic markers in liver tissue and decreased the extent of collagen-positive areas, as well as inhibited F4/80 macrophage aggregation and inflammatory cytokine secretion. The activation of adiponectin and FXR expression in hepatic tissue may be a major mechanistic signaling cascade supporting the promising role of AO in NAFLD pharmacotherapy. Collectively, our results demonstrated that AO extract improves non-alcoholic steatohepatitis (NASH) resolution, particularly with respect to NASH-related fibrosis, along with the regulation of liver enzymes, postprandial hyperglycemia, hyperlipidemia, and weight loss, probably through the modulation of the hepatic adiponectin and FXR pathways.


A composite hydrogel with co-delivery of antimicrobial peptides and platelet-rich plasma to enhance healing of infected wounds in diabetes.
Diabetic wound healing remains a major challenge due to its vulnerability to bacterial infection, as well as the less vascularization and prolonged inflammatory phase. In this study, we developed a hydrogel system for the treatment of chronic infected wounds, which can regulate inflammatory (through the use of antimicrobial peptides) and enhance collagen deposition and angiogenesis (through the addition of platelet-rich plasma (PRP)). Based on the formation of Schiff base linkage, the ODEX/HA-AMP/PRP hydrogel was prepared by mixing oxidized dextran (ODEX), antimicrobial peptide-modified hyaluronic acid (HA-AMP) and PRP under physiological conditions, which exhibited obvious inhibition zones against three pathogenic bacterial strains (E. coli, S. aureus and P. aeruginosa) and slow release ability of antimicrobials and growth factors. Moreover, CCK-8, live/dead fluorescent staining and scratch test confirmed that ODEX/HA-AMP/PRP hydrogel could facilitate the proliferation and migration of L929 fibroblast cells. More importantly, in vivo experiments further demonstrated that the prepared hydrogels could significantly improve wound healing in a diabetic mouse infection by regulating inflammation, accelerating collagen deposition and angiogenesis. In addition, prepared hydrogel showed a significant antibacterial activity against S. aureus and P. aeruginosa, inhibited pro-inflammatory factors (TNF-α, IL-1β and IL-6), enhanced anti-inflammatory factors (TGF-β1) and vascular endothelial growth factor (VEGF) production. The findings of this study suggested that the composite hydrogel with AMP and PRP controlled release ability could be used as a promising candidate for chronic wound healing and infection-related wound healing.