Characterization of the basal and pheromone-stimulated phosphorylation states of Ste12p.
The Saccharomyces cerevisiae transcription factor Ste12p is required for basal and activated expression of pheromone-responsive genes, and for invasive growth in haploid cells. In diploid yeast, Ste12p is implicated in pseudohyphal development. The ability of Ste12p to effect these various responses in three different cell types must require stringent regulation of its transcriptional activation function and interaction with additional transcription factors. We have examined the phosphorylation state of Ste12p in untreated and pheromone-treated haploid cells, and found eight constitutively phosphorylated peptides. Phosphorylation at the constitutive sites does not require the protein kinases of the pheromone-response pathway. Treatment of haploid yeast with mating pheromone causes the appearance of novel relatively minor phosphorylations on Ste12p. Brief [35S]methionine labeling reveals novel pheromone-dependent, electrophoretically slower migrating Ste12p species. Similarly, the sole difference we observe in tryptic phosphopeptides generated from Ste12p from pheromone-treated and untreated cells is the transient appearance of two novel minor hydrophobic phosphopeptides. The pheromone-dependent phosphorylation of Ste12p requires an intact pheromone-response pathway and localization of Ste12p to the nucleus, but does not require the Ste12p DNA-binding domain. We conclude from these experiments that the pheromone-response pathway induces the formation of specific hyperphosphorylation on Ste12p, which can only be detected as apparently minor modifications in vivo. We argue that, if Ste12p is regulated by direct pheromone-responsive phosphorylation, then that phosphorylation must be represented by the two novel phosphopeptides. However, we cannot exclude the possibility that pheromone-responsive transcription is controlled by direct phosphorylation of a target other than Ste12p.


A practical approach to imaging dyssynchrony for cardiac resynchronization therapy.
Cardiac resynchronization therapy (CRT) is believed to benefit patients by primarily correcting heterogeneity in regional ventricular mechanical contraction, known as dyssynchrony. Although many symptomatic heart failure patients with depressed left ventricular ejection fraction and widened electrocardiographic QRS complexes have clinical improvement from CRT, a significant subset of approximately one-third do not seem to respond. Because the degree of mechanical dyssynchrony may be widely variable, interest has remained high to attempt to improve patient selection for CRT using cardiac imaging as a means to quantify dyssynchrony. This article will review the principal echocardiographic methods of dyssynchrony analysis by tissue Doppler imaging, (opposing wall delay, 12-site standard deviation or Yu index, and longitudinal strain), routine pulsed-Doppler (interventricular mechanical delay, pre-ejection delay and filling time ratio), and speckle tracking (including radial, circumferential, and longitudinal strain). In addition, dyssynchrony analysis by cardiac magnetic resonance imaging is introduced as a potential alternative technique. The technical features, strengths and limitations, and clinical evidence for these methods are discussed, including a practical clinical approach.


Liquid Adhesive Contact Dermatitis After Bunionectomy: A Case Report and Literature Review.
Hypersensitivity reactions to the skin adherents used in postoperative dressings are an uncommon but unfavorable complication that can result in poor wound healing, increased scarring, and surgical wound infections. This unexpected and unforeseen complication is not well documented in the current published data. We present the case of a 39-year-old female who had undergone a bunionectomy procedure and developed allergic contact dermatitis postoperatively. We discuss the clinical findings and treatments administered after application of a commonly used liquid skin adhesive applied intraoperatively. Through the use of topical and oral steroids and foot soaks in astringent solutions, over the course of several months, the patient's skin returned to the expected postoperative appearance. With the increased consciousness to minimize surgical scarring to improve cosmesis, one of these causes of the reaction might have been the liquid adhesive used in the surgical closure and dressing application. Therefore, we additionally reviewed the adhesive compound's chemical makeup and any potential cross-reactivity to help surgeons make an informed decision of whether to use a liquid adhesive. The various ingredients in liquid adhesives contain known allergen compounds that can cause a reaction, such as balsam of Peru and colophony or rosin, both of which are reviewed in our report. We also present a treatment algorithm developed from the compiled data in the case of a patient developing an allergic reaction. From our literature review and considering the percentage of incidence, if a surgeon desires to use a liquid adhesive product, Mastisol(®) should be chosen because of its lower reactivity and greater adhesive properties compared with the compound tincture of benzoin.


Valvular aortic stenosis and coronary atherosclerosis: pathophysiology and clinical consequences.
New methods of investigation (ECG, echocardiography, angiography, histology) allow a better understanding of the pathophysiology of valvular aortic stenosis (VAS) associated with coronary atherosclerosis. The progressive decrease in valvular aortic area modifies the coronary blood flow and leads to myocardial ventricular hypertrophy. These two mechanisms worsen left ventricular function. A significant atherosclerotic stenosis on a large coronary artery creates a considerable reduction of the available coronary blood flow. This reduction is permanent: present at rest, it is obviously increased during exercise. The study of the relationship between the severity of the VAS and the myocardial hypertrophy (MH) is of great interest. It seems that in VAS with coronary artery disease, different situations exist: (i) when the hypertrophy is severe (left ventricular mass greater than 180 g m-2), the angina pectoris is more attributable to the VAS than to the coronary lesions. Thus the removal of the aortic outflow obstruction is the most essential therapy; (ii) when the hypertrophy is less severe (left ventricular mass less than 180 g m-2), surgical treatment of the valvular lesion and myocardial revascularization are justified.


Cross-Linking Induced Emission of Polymer Micelles for High-Contrast Visualization Level 3 Details of Latent Fingerprints.
Rationally developing an intelligent tool for high-contrast fluorescence imaging of latent fingerprints (LFPs) is gaining much concern in many applications such as medical diagnostics and forensic investigations. Herein, the off-on fluorescent polymer micelles (PMs) have been rationally designed and synthesized for high-contrast fluorescence imaging of LFPs through the cross-linking reaction of hydrazine (N2H4) and aldehyde group of polymer. Excitingly, the cross-linking (N2H4) induced emission of PMs has the property of aggregation-induced emission (AIE) and excited state intramolecular proton transfer (ESIPT), which could effectively address the notorious aggregation-caused quenching (ACQ) effects of conventional organic dyes. In addition, the cross-linking strategy can not only improve structural stability of PMs but also enhance its fluorescence brightness. The experiment results demonstrated that PMs showed high water dispersibility (100% aqueous solution), high selectivity, large Stokes shift (∼150 nm), good photostability, and excellent long-term stability. Because of the hydrophobic interaction between the PMs and fingerprint components, the PMs preferentially adhered onto the ridges of fingerprint, and then cross-linking (N2H4) induced emission properties endowed the PMs for high-contrast imaging of LFPs in different substrates, especially the levels 1-3 details of LFPs. We expect that this strategy will provide vital support for LFPs technology.


Silver-Lactoferrin Nanocomplexes as a Potent Antimicrobial Agent.
The process of silver immobilization onto and/or into bovine lactoferrin (LTF), the physicochemical properties of bovine lactoferrin and obtained silver-lactoferrin complexes, as well as antibacterial activity of silver-lactoferrin complexes were investigated in this work. Kinetic study of the silver immobilization into lactoferrin was carried out using batch sorption techniques. Spectrometric (MALDI-TOF/TOF-MS, ICP-MS), spectroscopic (FTIR, SERS), electron microscopic (TEM) and electrophoretic (I-DE) techniques, as well as zeta potential measurements, were applied for characterization of LTF and binding nature of silver in Ag-LTF complexes. On the basis of the results of the kinetics study, it was established that the silver binding to LTF is a heterogeneous process involving two main stages: (i) internal diffusion and sorption onto external surface of lactoferrin globules; and (ii) internal diffusion and binding into lactoferrin globule structure. Spectroscopic techniques combined with TEM analysis confirmed the binding process. Molecular dynamics (MD) analysis was carried out in order to simulate the mechanism of the binding process, and locate potential binding sites, as well as complement the experimental findings. Quantum mechanics (QM) simulations were performed utilizing density functional theory (DFT) in order to support the reduction mechanism of silver ions to elemental silver. Antimicrobial activity of synthesized lactoferrin complexes against selected clinical bacteria was confirmed using flow cytometry and antibiograms.


AMP-activated protein kinase (AMPK) activity negatively regulates chondrogenic differentiation.
Chondrocytes are derived from mesenchymal stem cells, and play an important role in cartilage formation. Sex determining region Y box (Sox) family transcription factors are essential for chondrogenic differentiation, whereas the intracellular signal pathways of Sox activation have not been clearly elucidated. AMP-activated protein kinase (AMPK) is a serine-threonine kinase generally regarded as a key regulator of cellular energy homeostasis. It is known that the catalytic alpha subunit of AMPK is activated by upstream AMPK kinases (AMPKKs) including liver kinase B1 (LKB1). We have previously reported that AMPK is a negative regulator of osteoblastic differentiation. Here, we have explored the role of AMPK in chondrogenic differentiation using in vitro culture models. The phosphorylation level of the catalytic AMPK alpha subunit significantly decreased during chondrogenic differentiation of primary chondrocyte precursors as well as ATDC-5, a well-characterized chondrogenic cell line. Treatment with metformin, an activator of AMPK, significantly reduced cartilage matrix formation and inhibited gene expression of sox6, sox9, col2a1 and aggrecan core protein (acp). Thus, chondrocyte differentiation is functionally associated with decreased AMPK activity.


A comparison between four techniques to measure cardiac output.
Cardiac output is an important variable when monitoring hemodynamic status. In particular, changes in cardiac output represent the goal of several circulatory management therapies. Unfortunately, cardiac output is very difficult to estimate, either in experimental or clinical settings. The goal of this work is to compare four techniques to measure cardiac output: pressure-volume catheter, aortic flow probe, thermodilution, and the PiCCO monitor. These four techniques were simultaneously used during experiments of fluid and endotoxin administration on 7 pigs. Findings show that, first, each individual technique is precise, with a relative coefficient of repeatability lower than 7 %. Second, 1 cardiac output estimate provided by any technique relates poorly to the estimates from the other 3, even if there is only small bias between the techniques. Third, changes in cardiac output detected by one technique are only detected by the others in 62 to 100 % of cases. This study confirms the difficulty of obtaining a reliable clinical cardiac output measurement. Therefore, several measurements using different techniques should be performed, if possible, and all such should be treated with caution.


Adsorption of Selenium and Strontium on Goethite: EXAFS Study and Surface Complexation Modeling of the Ternary Systems.
Knowledge of the geochemical behavior of selenium and strontium is critical for the safe disposal of radioactive wastes. Goethite, as one of the most thermodynamically stable and commonly occurring natural iron oxy-hydroxides, promisingly retains these elements. This work comprehensively studies the adsorption of Se(IV) and Sr(II) on goethite. Starting from electrokinetic measurements, the binary and ternary adsorption systems are investigated and systematically compared via batch experiments, EXAFS analysis, and CD-MUSIC modeling. Se(IV) forms bidentate inner-sphere surface complexes, while Sr(II) is assumed to form outer-sphere complexes at low and intermediate pH and inner-sphere complexes at high pH. Instead of a direct interaction between Se(IV) and Sr(II), our results indicate an electrostatically driven mutual enhancement of adsorption. Adsorption of Sr(II) is promoted by an average factor of 5 within the typical groundwater pH range from 6 to 8 for the concentration range studied here. However, the interaction between Se(IV) and Sr(II) at the surface is two-sided, Se(IV) promotes Sr(II) outer-sphere adsorption, but competes for inner-sphere adsorption sites at high pH. The complexity of surfaces is highlighted by the inability of adsorption models to predict isoelectric points without additional constraints.


Enhanced retention in the passive-avoidance task by 5-HT(1A) receptor blockade is not associated with increased activity of the central nucleus of the amygdala.
The effect of blockade of 5-HT1A receptors was investigated on (1). retention in a mildly aversive passive-avoidance task, and (2). spontaneous single-unit activity of central nucleus of the amygdala (CeA) neurons, a brain site implicated in modulation of retention. Systemic administration of the selective 5-HT1A antagonist NAN-190 immediately after training markedly-and dose-dependently-facilitated retention in the passive-avoidance task; enhanced retention was time-dependent and was not attributable to variations in wattages of shock received by animals. Systemic administration of NAN-190 had mixed effects on spontaneous single-unit activity of CeA neurons recorded extracellularly in vivo; microiontophoretic application of 5-HT, in contrast, consistently and potently suppressed CeA activity. The present findings-that 5-HT1A receptor blockade by NAN-190 (1). enhances retention in the passive-avoidance task, and (2). does not consistently increase spontaneous neuronal activity of the CeA-provide evidence that a serotonergic system tonically inhibits modulation of retention in the passive-avoidance task through activation of the 5-HT1A receptor subtype at brain sites located outside the CeA.


Alzheimer's disease and vascular factors: facts and theories.
Although Alzheimer s disease is classified as a neurodegenerative dementia, in Alzheimer s dementia there is increasing evidence of an association with vascular risk factors and vascular pathology. These observations are supported by epidemiological and pathological studies. Vascular factors may play a significant role in the pathogenesis of Alzheimer s dementia. Further research is needed to explore this relationship. Modification of vascular risk factors could make a significant impact towards prevention and treatment of Alzheimer s disease, which is a distressing and prevalent condition in the community. This article considers the relationship of these vascular risk factors and potential mechanisms associated with the aetiopathogenesis of Alzheimer s dementia.


Growth and Performance of Guar (Cyamopsis tetragonoloba (L.) Taub.) Genotypes under Various Irrigation Regimes with and without Biogenic Silica Amendment in Arid Southwest US.
Guar is a potential crop that can be grown as a forage or as a seed crop in arid to semi-arid regions due to its low water requirements and tolerance to heat. Optimizing irrigation water use is important for making alternative crops such as guar a sustainable option. Amendments such as biogenic silica, a sedimentary rock from a biogenic source such as fossils, may help plants tolerate water stress due to reduced irrigation. The objective of the current study was to evaluate seed yield and attribute components and agronomic and physiological parameters for four guar genotypes (Matador, Kinman, Lewis, and NMSU 15-G1) under five drip irrigation regimes (I1-normal irrigation, I2-no irrigation at 75% pod formation, I3-no irrigation at 50% and 75% pod formation, I4-terminate irrigation at flowering, and I5-terminate irrigation at flowering + biogenic silica amendment) at Las Cruces in southern New Mexico, USA, from 2016 to 2018. On average, the I1 irrigation regime produced the highest guar seed yield (2715 kg ha-1) followed by I5 (2469 kg ha-1) from 2016 to 2018. As compared to the I1 regime, the I2 and I3 regimes resulted in a 20.8% and 23.4% decline in guar seed yield, respectively, on average from 2016 to 2018. The results suggest that the addition of biogenic silica might help to improve guar seed yield under reduced irrigation conditions and can produce comparable yields with an average of 300 mm of irrigation during the growing season in the southern New Mexico region of the Southwest US.


Angiotensin-II-induced reactive oxygen species along the SFO-PVN-RVLM pathway: implications in neurogenic hypertension.
Neurogenic hypertension has been the subject of extensive research worldwide. This review is based on the premise that some forms of neurogenic hypertension are caused in part by the formation of angiotensin-II (Ang-II)-induced reactive oxygen species along the subfornical organ-paraventricular nucleus of the hypothalamus-rostral ventrolateral medulla pathway (SFO-PVN-RVLM pathway). We will discuss the recent contribution of our laboratory and others regarding the mechanisms by which neurons in the SFO (an important circumventricular organ) are activated by Ang-II, how the SFO communicates with two other important areas involved in sympathetic activity regulation (PVN and RVLM) and how Ang-II-induced reactive oxygen species participate along the SFO-PVN-RVLM pathway in the pathogenesis of neurogenic hypertension.


Pea hull fiber supplementation does not modulate uremic metabolites in adults receiving hemodialysis: a randomized, double-blind, controlled trial.
Fiber is a potential therapeutic to suppress microbiota-generated uremic molecules. This study aimed to determine if fiber supplementation decreased serum levels of uremic molecules through the modulation of gut microbiota in adults undergoing hemodialysis. A randomized, double-blinded, controlled crossover study was conducted. Following a 1-week baseline, participants consumed muffins with added pea hull fiber (PHF) (15 g/d) and control muffins daily, each for 4 weeks, separated by a 4-week washout. Blood and stool samples were collected per period. Serum p-cresyl sulfate (PCS), indoxyl sulfate (IS), phenylacetylglutamine (PAG), and trimethylamine N-oxide (TMAO) were quantified by LC-MS/MS, and fecal microbiota profiled by 16S rRNA gene amplicon sequencing and specific taxa of interest by qPCR. QIIME 2 sample-classifier was used to discover unique microbiota profiles due to the consumption of PHF. Intake of PHF contributed an additional 9 g/d of dietary fiber to the subjects' diet due to compliance. No significant changes from baseline were observed in serum PCS, IS, PAG, or TMAO, or for the relative quantification of Akkermansia muciniphila, Faecalibacterium prausnitzii, Bifidobacterium, or Roseburia, taxa considered health-enhancing. Dietary protein intake and IS (r = -0.5, p = 0.05) and slow transit stool form and PCS (r = 0.7, p < 0.01) were significantly correlated at baseline. PHF and control periods were not differentiated; however, using machine learning, taxa most distinguishing the microbiota composition during the PHF periods compared to usual diet alone were enriched Gemmiger, Collinsella, and depleted Lactobacillus, Ruminococcus, Coprococcus, and Mogibacteriaceae. PHF supplementation did not mitigate serum levels of targeted microbial-generated uremic molecules. Given the high cellulose content, which may be resistant to fermentation, PHF may not exert sufficient effects on microbiota composition to modulate its activity at the dose consumed.


Quantitative approaches to in vivo brain microdialysis.
The microdialysis technique has been widely used for the study of extracellular chemical events in various tissues. Until recently, however, little was known about the sampling characteristics of dialysis probes in vivo. The purpose of this review is to describe several theoretical models of in vivo microdialysis that consider both the diffusional resistances encountered in vivo and the effects of various active processes, such as metabolism, release and uptake, and transport across the blood brain barrier. The relevance of the models to practical in vivo microdialysis experiments is discussed. Several microdialysis techniques that quantitatively estimate extracellular analyte concentrations are also reviewed. These techniques are discussed in relation to the theoretical models, together with a discussion of the experimental factors that affect in vivo microdialysis experiments.


VEGFA Involves in the Use of Fluvastatin and Zoledronate Against Breast Cancer.
Our study aimed to identify key genes involved in the use of fluvastatin and zoledronate against breast cancer, as well as to investigate the roles of vascular endothelial growth factor A (VEGFA) in the malignant behaviors of breast cancer cells. The expression data GSE33552 was downloaded from Gene Expression Omnibus database, including mocked-, fluvastatin- and zoledronate-treated MDA-MB-231 cells. Differentially expressed genes (DEGs) were identified in fluvastatin- and zoledronate-treated cells using limma package, respectively. Pathway enrichment analysis and protein-protein interaction (PPI) network analysis were then performed. Then we used shRNA specifically targeting VEGFA (shVEGFA) to knock down the expression of VEGFA in MDA-MB-231 cells. Cell viability assay, scratch wound healing assay, Transwell invasion assay and flow cytometry were performed to explore the effects of VEGFA knockdown on the malignant behaviors of breast cancer cells. VEGFA was up-regulated in both fluvastatin- and zoledronate-treated breast cancer cells. Moreover, VEGFA was a hub node in PPI network. In addition, VEGFA was successfully knocked down in MDA-MB-231 cells by shVEGFA. Suppression of VEGFA promoted the migration and invasion of breast cancer MDA-MB-231 cells. Suppression of VEGFA inhibited the apoptosis of MDA-MB-231 cells. Our results indicate that up-regulation of VEGFA may prevent the progression of breast cancer after fluvastatin and zoledronate treatment via inducing cell apoptosis and inhibiting migration and invasion. VEGFA may serve as a potential prognostic indicator for clinical outcome in the management of breast cancer.


Phagocytosis of Mycobacterium leprae by human monocyte-derived macrophages is mediated by complement receptors CR1 (CD35), CR3 (CD11b/CD18), and CR4 (CD11c/CD18) and IFN-gamma activation inhibits complement receptor function and phagocytosis of this bacterium.
We have examined phagocytosis of Mycobacterium leprae by human monocyte-derived macrophages (MDM). Compared with monocytes, MDM exhibit greatly enhanced adherence of M. leprae (6.5 +/- 2-fold increase). MDM adherence of M. leprae is serum dependent and requires heat-labile serum components because heat inactivation of serum reduces adherence by 70 +/- 3%. mAb against C receptors CR1 (CD35), CR3 (CD11b/CD18), and CR4 (CD11c/CD18) inhibit phagocytosis of M. leprae in fresh nonimmune serum. Single mAb against each receptor inhibit M. leprae adherence by 25 +/- 4% - 33 +/- 6%. Single mAb used in combination against all three receptors inhibit M. leprae adherence by 51 +/- 6%. Most significantly, pairs of mAb used in combination against all three receptors inhibit by 80 +/- 4%. By electron microscopy, MDM ingest all M. leprae that adhere in fresh nonimmune serum. In the presence of mAb against CR1, CR3, and CR4, the percentage of MDM cross-sections that contain intracellular bacteria is reduced 66 +/- 3% and the mean number of bacteria per cross-section is reduced 78 +/- 10%. MDM activated by IFN-gamma exhibit markedly reduced adherence (by light microscopy) and ingestion (by electron microscopy) of M. leprae. MDM in culture for 5 days inhibit M. leprae adherence by 83 +/- 2% and ingestion by 88% when activated for 5 days. Paralleling this, IFN-gamma-activated MDM exhibit markedly reduced C receptor function, reflected by markedly decreased adherence and ingestion of C3b- and C3bi-coated E. Decreased C receptor function by IFN-gamma-activated MDM correlates with decreased surface expression of CR1 but not CR3 or CR4. CR1 expression on MDM in culture for 5 days is reduced by 32 +/- 9% and 75 +/- 3% after IFN-gamma activation for 5 and 2 days, respectively. This study demonstrates that MDM have an enhanced capacity to phagocytize M. leprae, and that in addition to CR1 and CR3, phagocytosis involves CR4, whose expression on MDM is highly maturation-dependent. This study also demonstrates that IFN-gamma activation markedly reduces the capacity of MDM to phagocytize M. leprae, and it provides a molecular mechanism for this phenomenon-decreased C receptor function.


Imaging of infection and inflammation with an improved 99mTc-labeled LTB4 antagonist.
Studies have demonstrated that the bivalent (111)In-labeled leukotriene B4 (LTB4) antagonist DPC11870 reveals infectious and inflammatory lesions in various rabbit models. The radioactive tracer accumulates quickly at the site of infection and clears rapidly from the circulation, resulting in high-quality images. In this study, 2 new hydrazinonicotinamide (HYNIC)-conjugated compounds that are structurally related to DPC11870 were studied to further improve image quality. A bivalent HYNIC-conjugated LTB4 antagonist (MB81) and a monovalent one (MB88) were labeled with (99m)Tc. The radiolabeled compounds were intravenously injected into New Zealand White rabbits with E. coli infection in the left thigh muscle. The imaging characteristics of both compounds were compared with those of the bivalent (111)In-labeled LTB4 antagonist. Both (99m)Tc-labeled LTB4 antagonists revealed the abscess from 2 h after injection onward. Abscess uptake at 8 h after injection was similar for both compounds (0.22 +/- 0.08 percentage injected dose per gram [%ID/g] and 0.36 +/- 0.13%ID/g for the bivalent and monovalent compounds, respectively). However, visualization of the abscess and the quality of the images were better after injection of MB88 than after injection of either of the bivalent LTB4 antagonists. The excellent delineation of the abscess by MB88 was mainly due to the more rapid clearance of this compound from nontarget organs. The (99m)Tc-labeled HYNIC conjugated LTB4 antagonists MB88 and MB81 revealed infectious foci in rabbits within a few hours after injection. Imaging characteristics of monovalent (99m)Tc-MB88 were superior to those of the bivalent LTB4 antagonists DPC11870 and MB81. Therefore, of the 3 LTB4 antagonists, the monovalent LTB4 antagonist MB88 is the most potent and promising agent for visualizing and evaluating infection and inflammation in patients.


[A report on investigation of an outbreak of Legionnaires' disease in a hotel in Beijing].
During the period from February to March, 1992, an outbreak of upper respiratory infection (influenza-like syndrome) took place in a hotel in Beijing. An epidemiological investigation and bacteriological examination were carried out in this hotel. The results showed that it was an outbreak of Legionnaires' disease caused by Legionella pneumophila serogroup 10 (Lp10): The incidence was 13.51% (5/37). This is the first report on LP10 infection in China.


2-Year GLOBE trial results: telbivudine Is superior to lamivudine in patients with chronic hepatitis B.
The GLOBE trial has compared the efficacy and safety of telbivudine versus lamivudine treatment over 2 years in patients with chronic hepatitis B. Hepatitis B e antigen (HBeAg)-positive (n = 921) and HBeAg-negative (n = 446) patients received telbivudine or lamivudine once daily for 104 weeks. The primary outcome, assessed in the intent-to-treat population, was therapeutic response (hepatitis B virus DNA <5 log(10) copies/mL and either HBeAg loss or normalization of alanine aminotransferase [ALT] level). The therapeutic response to telbivudine was superior to that of lamivudine in HBeAg-positive (63% vs 48%; P < .001) and HBeAg-negative (78% vs 66%; P = .007) patients. HBeAg-positive patients given telbivudine also had better outcomes compared with lamivudine in terms of nondetectable viremia (< 300 copies/mL) at 55.6% versus 38.5% (P < .001), HBeAg loss at 35.2% versus 29.2% (P = .056), and viral resistance at 25.1% versus 39.5% (P < .001). Hepatitis B e antigen seroconversion was 29.6% versus 24.7% (P = .095) in all patients and 36% versus 27% (P = .022) in patients with baseline ALT level > or = 2 times normal. Telbivudine-treated HBeAg-negative patients showed higher rates of nondetectable viremia compared with lamivudine at 82.0% versus 56.7% (P < .001) and less resistance at 10.8% versus 25.9% (P < .001). Adverse events occurred with similar frequency, whereas grade 3/4 increases in creatine kinase levels were more common in patients given telbivudine (12.9% vs 4.1%, P < .001). Multivariate logistic regression analyses identified telbivudine treatment, among other variables, as an independent predictor of better week 104 outcomes. Telbivudine is superior to lamivudine in treating patients with chronic hepatitis B over a 2-year period.


Comparative Safety, Immunogenicity, and Efficacy of CEF Cell-Based and DF-1 Cell Line Adapted Infectious Bursal Disease Vaccines in Specific-Pathogen-Free Chickens.
Infectious bursal disease (IBD) is an immunosuppressive and economically important disease of young chickens caused by infectious bursal disease virus (IBDV). The National Veterinary Institute (Bishoftu, Ethiopia) produces intermediate IBDV vaccine using primary chicken embryo fibroblast (CEF) cells, a method with technical and economical cumbersome. This study assessed the safety, immunogenicity, and efficacy of DF-1 cell line-adapted IBDV LC-75 vaccine strain in reference to the CEF-based vaccine. Confluent monolayer of DF-1 cells was infected with IBDV and cells with cytopathic effects were passaged until 3rd passage. Viral growth was confirmed using a one-step RT-PCR targeting IBDV VP2 gene. Viral titer increased from 1st passage through 3rd passage. Safety was assessed in 30 specific-pathogen-free chickens (15 chickens/group) injected with 10-fold field dose of each vaccine intraocularly and monitored for 21 days. For immunogenicity and efficacy, 60 specific-pathogen-free chickens were grouped into 3 (20 chickens/group). First and 2nd group received DF-1 cell and CEF-based IBDV vaccines, respectively. The 3rd group served as unvaccinated control. Antibody response was measured using iELISA. Chickens were challenged 4 weeks postvaccination with very virulent IBDV (vvIBDV) intraocularly and followed-up for 10 days. Vaccination did not cause any adverse reactions during the 21 days of follow-up. In addition, both vaccines induced higher antibody titer 14 and 24 days-post-vaccination as compared to unvaccinated controls (p < 0.05). Moreover, DF-1 and CEF-based IBDV LC-75 vaccines rendered a complete protection against vvIBDV. Contrarily, morbidity and mortality in unvaccinated chickens was 50% and 30%, respectively. The results indicated that DF-1 and CEF cell-based IBDV vaccines are comparably immunogenic and efficacious. Therefore, DF-1 cell-line can be considered an affordable and convenient alternative to the CEF-based approach. The suitability of DF-1 cells to grow other IBDV strains and safety of these vaccines on bursa of Fabricius should further be investigated.


Antigen detection with monoclonal antibodies for the diagnosis of adenovirus gastroenteritis.
A monoclonal antibody-based enzyme immunoassay (EIA) was developed for direct detection of enteric adenoviruses in stool specimens from individuals with gastroenteritis. Tests specific for each of the enteric adenoviruses, adenovirus type 40 (Ad 40) and type 41 (Ad 41), were designed. The sensitivity of the assay was determined by comparing the results of the EIA with isolation of virus in Graham 293 cells from stools that contained particles having adenovirus morphology. The standard for specificity was analysis of adenovirus genome profiles after digestion with SmaI endonuclease. The sensitivity was 95.8% (23 of 24) for Ad 40 and 97.1% (34 of 35) for Ad 41. The specificity was 95.7% (45 of 47) and 97.2% (35 of 36), respectively. The two type-specific monoclonal antibodies could be mixed in an EIA for identification of enteric adenoviruses in stools without loss of reactivity in either type. The EIA permits rapid diagnosis and type-specific identification of enteric adenoviruses in gastroenteritis.


Scanning laser optical computed tomography system for large volume 3D dosimetry.
Stray light causes artifacts in optical computed tomography (CT) that negatively affect the accuracy of radiation dosimetry in gels or solids. Scatter effects are exacerbated by a large dosimeter volume, which is desirable for direct verification of modern radiotherapy treatment plans such as multiple-isocenter radiosurgery. The goal in this study was to design and characterize an optical CT system that achieves high accuracy primary transmission measurements through effective stray light rejection, while maintaining sufficient scan speed for practical application. We present an optical imaging platform that uses a galvanometer mirror for horizontal scanning, and a translation stage for vertical movement of a laser beam and small area detector for minimal stray light production and acceptance. This is coupled with a custom lens-shaped optical CT aquarium for parallel ray sampling of projections. The scanner images 15 cm diameter, 12 cm height cylindrical volumes at 0.33 mm resolution in approximately 30 min. Attenuation coefficients reconstructed from CT scans agreed with independent cuvette measurements within 2% for both absorbing and scattering solutions as well as small 1.25 cm diameter absorbing phantoms placed within a large, scattering medium that mimics gel. Excellent linearity between the optical CT scanner and the independent measurement was observed for solutions with between 90% and 2% transmission. These results indicate that the scanner should achieve highly accurate dosimetry of large volume dosimeters in a reasonable timeframe for clinical application to radiotherapy dose verification procedures.


The GSTome Reflects the Chemical Environment of White-Rot Fungi.
White-rot fungi possess the unique ability to degrade and mineralize all the different components of wood. In other respects, wood durability, among other factors, is due to the presence of extractives that are potential antimicrobial molecules. To cope with these molecules, wood decay fungi have developed a complex detoxification network including glutathione transferases (GST). The interactions between GSTs from two white-rot fungi, Trametes versicolor and Phanerochaete chrysosporium, and an environmental library of wood extracts have been studied. The results demonstrate that the specificity of these interactions is closely related to the chemical composition of the extracts in accordance with the tree species and their localization inside the wood (sapwood vs heartwood vs knotwood). These data suggest that the fungal GSTome could reflect the chemical environment encountered by these fungi during wood degradation and could be a way to study their adaptation to their way of life.


Occupational health in the Philippines.
The practice of occupational health and safety (OHS) in the Philippines is shaped by both success and failures. Government initiatives have achieved specific goals, particularly in providing better access by local industries to technical services and manpower development. However, the ability to sustain these achievements has been constrained by lack of adequate resources, both financial and human. Large-scale industrial establishments have better success in the implementation of OHS programs in their organizations. Small- and medium-scale enterprises suffer from limited resources to invest in measures for the health and safety of workers. Similarly, the government has little influence on the health and safety conditions migrant workers experience in another nation. The informal sector is the most deprived in terms of access to OHS measures. The deprivation may be alleviated by economic solutions, as their existence is a result of economic situations. Occupational health development in the Philippines is progressing and will be strengthened by better regulation, by increasing awareness among all sector workers of the importance of OHS, and by adequately building up the capacity of government and vital human resources.


Haber's Syndrome: A Case Report.
Haber's syndrome is an autosomal dominant, rare genodermatosis characterized by photosensitive, persistent facial erythema associated with reticulated hyperpigmentation. We present a case of an eight-year-old healthy Saudi girl who presented with facial erythema and generalized reticulated hyperpigmentation. Systematic review and laboratory studies were unremarkable. Histopathological examination revealed hyperpigmentation of the basilar keratinocytes with mild digitated elongations of the rete ridges. The patient was diagnosed with early-onset clinical presentation of Haber's syndrome. In this report, Haber's syndrome is reviewed, and differential diagnoses of reticulated hyperpigmentation are discussed.


Comparison of pharmacokinetics of marbofloxacin after subcutaneous administration of various multiple-dose regimens to water buffalo calves (Bubalus bubalis).
To determine pharmacokinetics of marbofloxacin in water buffalo calves (Bubalus bubalis) after multiple SC administrations and to assess differences in regimen efficacy. 18 healthy buffalo calves. Calves (n = 6 calves/group) were assigned to receive marbofloxacin SC in the neck at 1 of 3 dosages (2 mg/kg, q 24 h for 6 days [regimen 1]; 4 mg/kg, q 48 h for 6 days [regimen 2]; and 4 mg/kg, q 24 h for 3 days [regimen 3]). Serum marbofloxacin concentrations were analyzed. Efficacy predictors were estimated on the basis of minimum inhibitory concentration and mutant prevention concentration reported for Pasteurella multocida and Mannheimia haemolytica. Mean ± SD area under the concentration-time curve was 5.92 ± 0.40 μg•h/mL for regimen 1, which differed significantly from that for regimens 2 (14.26 ± 0.92 μg•h/mL) and 3 (14.17 ± 0.51 μg•h/mL). Mean residence time and mean elimination half-life for regimen 2 (9.93 ± 0.20 hours and 8.77 ± 0.71 hours) both differed significantly from those for regimens 1 (721 ± 0.11 hours and 5.71 ± 0.38 hours) and 3 (759 ± 0.13 hours and 737 ± 1.19 hours). Values obtained from indices for P multocida and M haemolytica had an excessively wide range because of the various degrees of antimicrobial susceptibility (low, medium, and high) of the strains. Regimen 3 had the most favorable indices, and it would be conducive for owner compliance and require less handling of animals.


Traps of carnivorous pitcher plants as a habitat: composition of the fluid, biodiversity and mutualistic activities.
Carnivorous pitcher plants (CPPs) use cone-shaped leaves to trap animals for nutrient supply but are not able to kill all intruders of their traps. Numerous species, ranging from bacteria to vertrebrates, survive and propagate in the otherwise deadly traps. This paper reviews the literature on phytotelmata of CPPs. Fluid as a Habitat The volumes of pitchers range from 0·2 mL to 1·5 L. In Nepenthes and Cephalotus, the fluid is secreted by the trap; the other genera collect rain water. The fluid is usually acidic, rich in O(2) and contains digestive enzymes. In some taxa, toxins or detergents are found, or the fluid is extremely viscous. In Heliamphora or Sarracenia, the fluid differs little from pure water. Diversity Pitcher inquilines comprise bacteria, protozoa, algae, fungi, rotifers, crustaceans, arachnids, insects and amphibia. The dominant groups are protists and Dipteran larvae. The various species of CPPs host different sets of inquilines. Sarracenia purpurea hosts up to 165 species of inquilines, followed by Nepenthes ampullaria with 59 species, compared with only three species from Brocchinia reducta. Reasons for these differences include size, the life span of the pitcher as well as its fluid. MUTUALISTIC: Activities Inquilines closely interact with their host. Some live as parasites, but the vast majority are mutualists. Beneficial activities include secretion of enzymes, feeding on the plant's prey and successive excretion of inorganic nutrients, mechanical break up of the prey, removal of excessive prey and assimilation of atmospheric N(2). There is strong evidence that CPPs influence their phytotelm. Two strategies can be distinguished: (1) Nepenthes and Cephalotus produce acidic, toxic or digestive fluids and host a limited diversity of inquilines. (2) Genera without efficient enzymes such as Sarracenia or Heliamphora host diverse organisms and depend to a large extent on their symbionts for prey utilization.


Neurite outgrowth properties of Calotropis procera: In search for a neuroprotectant.
In view of the well-documented medicinal properties of Calotropis procera (CP), the present study was designed to evaluate the neuroprotective effect of the extract. We have prepared a methanolic extract of Calotropis procera and screen varying concentration of CP (20, 30, 40, 50 and 70μg/ml) for the stimulatory potency on neurite outgrowth. The stimulatory effect of CP on neurite outgrowth was assessed in primary hippocampal neurons. Neurite lengths were measured using optika provison analysis software. Neuritogenesis was further analyzed by immunostaining by using specific neuronal marker β III-tubulin. The data show that neurite outgrowth from hippocampal neurons were significantly enhanced in the presence of CP (40μg/ml). The most stimulatory neurite outgrowth effects were appeared after 48hrs incubation of neurons with CP (40μg/ml). These data confirm that CP extract could promote invitro hippocampal neurite outgrowth in a dose-dependent manner. Our results indicate that CP can be used as a healthy dietary supplement for the cognitive functions of the brain.


Mitosis trumps T stage and proposed international association for the study of lung cancer/american thoracic society/european respiratory society classification for prognostic value in resected stage 1 lung adenocarcinoma.
We investigated whether a group of pathologists could reproducibly apply the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification for lung adenocarcinoma to a cohort of stage 1 tumors and whether this architectural classification and/or other parameters could demonstrate survival advantage. A total of 145 cases of 7 edition of tumor, node, metastasis stage 1 adenocarcinoma were retrospectively reviewed for predominant architectural pattern, including cribriform pattern, nuclear grade, mitotic index, and necrosis. The parameters were assessed for reproducibility and survival and using multivariate analysis, compared with stage, age, and sex. The majority of tumors had a mixed architecture with the acinar pattern being the most common predominant architecture. Micropapillary and cribriform architecture were the least frequent patterns. This study demonstrated that a group of five pathologists could reproducibly apply the IASLC/ATS/ERS classification. Although there were insufficient cribriform-predominant adenocarcinomas for assessment, when the percentage of all cribriform was combined with other architectures, it was associated with a worse prognosis. The majority of the parameters assessed demonstrated significance with univariate analysis but only mitotic index, as assessed by the highest count/10 high-power fields remained significant with multivariate analysis. In this study of resected stage 1 primary lung adenocarcinoma, we found mitotic index to be the only independent prognostic marker. It was more closely associated with outcome than either pathologic T stage or IASLC/ATS/ERS architecture-based classification. Further validation of concordance and reproducibility in reporting mitotic index, as well as validation of prognostic significance, needs to be undertaken in independent data sets.


Immunological evaluation of personalized peptide vaccination for patients with pancreatic cancer.
The prognosis of pancreatic cancer is extremely poor, and development of new treatment modalities is needed. One such treatment could be specific immunotherapy. To evaluate safety and immunological responses, we conducted a phase I study of personalized peptide vaccination for pancreatic cancer patients (n=11). Namely, pre-vaccination peripheral blood mononuclear cells were screened for their reactivity in vitro to each of 14 or 16 peptides in HLA-A24(+) or -A2(+) patients, and only the reactive peptides (maximum: 4) were vaccinated in vivo. This regimen was generally well tolerated, although inflammatory reactions at the injection site were observed in 7 patients. Delayed-type hypersensitivity to peptides used for vaccination was observed in 7 patients. Increased cellular and humoral immune responses to at least one of peptides used for vaccination were observed in the post-vaccination PBMCs and sera from 4 of 8 patients and 4 of 10 patients tested, respectively. The 6- and 12-month survival rates for patients who received >3 vaccinations (n=10) were 80% and 20%, respectively. Due to tolerability and capability of inducing specific immunity, further development of personalized peptide-based immunotherapy for pancreatic cancer patients is warranted.


Controlling synchrony by delay coupling in networks: from in-phase to splay and cluster states.
We study synchronization in delay-coupled oscillator networks using a master stability function approach. Within a generic model of Stuart-Landau oscillators (normal form of supercritical or subcritical Hopf bifurcation), we derive analytical stability conditions and demonstrate that by tuning the coupling phase one can easily control the stability of synchronous periodic states. We propose the coupling phase as a crucial control parameter to switch between in-phase synchronization or desynchronization for general network topologies or between in-phase, cluster, or splay states in unidirectional rings. Our results are robust even for slightly nonidentical elements of the network.


Effect of surfactant on water-soluble conjugated polymer used in biosensor.
The effect of nonionic surfactants on the cationic conjugated polymer (CCP), poly{9,9-bis[6-(N,N-trimethylammonium)hexyl]fluorene-co 1,4-phenylene} iodide 1, has been investigated. It is shown that the CCP in various solvents exists in three phases: isolated polymer chains, polymer aggregate, and variable size clusters (partially dissolved polymer). It is shown that nonionic surfactants enhance the photoluminescence (PL) quantum yield of the CCP in water by breakup of polymer aggregates, which eliminates the nonemissive interchain quenching with aggregates and increases surface-to-volume ratio of the CCP. Furthermore, the surfactants reduce quenching by incorporation of the CCP into aggregates or binary micelles. Surfactant also reduces the polar interaction strength between CCP and water and enhances CCP quenching by the counterions (iodine) by ion pairing effect. The dynamics of the interactions are complex and reveal that the surfactant induces rapid increase in the PL which imply that the main force that causes the aggregation is weak and may be due to hydrophobic interaction of the CCP in water rather than a solid, particulate-like state. Time-resolved fluorescence measurements at the exciton energy (420 nm) confirm that the CCP in water and in some organic solvents is a multiphase system in which three exponential decay terms are needed to fit the decay profile of the CCP. The change in the decay lifetime explains clearly the effect of surfactant and solvent polarity on the three CCP phases. The average lifetime of the CCP does not increase with surfactant, but the number of isolated polymer chains increases which leads to higher PL quantum yield. The association between the polymer and a quencher, single-strand deoxyribonucleic acid (ssDNA), was investigated. It indicated that CCP:ssDNA forms a weak electrostatic complex that does not alter the absorption spectra of the CCP but induces a strong CCP fluorescence quenching with association constant KS = 5 x 10(7) M(-1). At low ssDNA concentrations, the surfactant reduces quenching in the complex possibly by preventing charge-transfer processes. This may be due to an increase in the distance between the CCP and ssDNA through incorporation of the CCP into aggregates (micelles). However, at high ssDNA concentration, the quenching increases sharply which may be assigned to the increase in the electrostatic force destroying the micelles' structure around the CCP, leading to contact quenching as well as DNA induced CCP aggregation, which in turn leads to CCP-CCP quenching.


Decision making in advanced cancer of the head and neck: variation in the views of medical specialists.
Forty specialists were asked about their management of three theoretical patients with advanced cancer of the head and neck. Reasons for variation were explored by considering the influence of perceived aims of treatment (radical or palliative), together with a number of factors relating to the tumour, the lymph nodes, and the patients' personal circumstances. The perceived aim of treatment was the most important determinant as to treatment modality but, when chances of influencing survival were small, there was disagreement as to the appropriate aim and subjective value judgements became influential. More careful analysis of the initial decision-making process is needed if new clinical trials are to significantly affect clinical practices.


A Study of the Monohydrate and Dihydrate Complexes of Perfluoropropionic Acid Using Chirped-Pulse Fourier Transform Microwave (CP-FTMW) Spectroscopy.
This work reports the first known spectroscopic observation of the monohydrate and dihydrate complexes of perfluoropropionic acid (PFPA). The spectra have been observed using a chirped-pulse Fourier transform microwave (CP-FTMW) spectrometer in the 7750 to 14,250 MHz region. The structures of the species have been confirmed with the aid of ab initio quantum chemical calculations. Rotational constants A, B, and C have been determined and reported for both species along with centrifugal distortion constants ΔJ, ΔJK, ΔK, δJ, δK for H2O-PFPA and ΔJ, ΔJK, and δJ for (H2O)2-PFPA. Effects due to large amplitude motions were not observable in these experiments. Structures of the complexes have been determined using a combination of experimental second moment values and ab initio results. The complexation of the -OH of one or two water molecules has been found to occur in the plane of the carboxylic acid group forming a six- or eight-member ring.


Indications and outcomes for use of Montgomery cannulas.
To our knowledge, we report the first series to analyze use of the Montgomery cannula as an airway management tool for indications other than obstructive sleep apnea. To analyze the use and outcomes of Montgomery cannula placement for airway management and to identify indications for placement. Retrospective review of 20 patients who received a Montgomery cannula from 2003 through 2012 at the University of Iowa Hospitals and Clinics. Montgomery cannula placement. Indications for cannula placement, comorbidities, body mass index, reasons for failure of cannula use, and complications. Indications included glottic stenosis (n = 7), obstructive sleep apnea (n = 5), bilateral vocal cord paralysis (n = 4), subglottic stenosis (n = 4), supraglottic swelling after radiation or chemoradiation therapy (n = 4), bulbar dystonia with paradoxical vocal cord motion (n = 1), vocal cord fixation secondary to rheumatoid arthritis and gastroesophageal reflux disease (n = 1), and airway obstruction associated with seizure disorder (n = 1). Comorbidities included obesity or overweight (n = 14), gastroesophageal reflux disease (n = 9), hypertension (n = 7), and diabetes mellitus (n = 6). Fifteen patients successfully used a Montgomery cannula, including all patients with 3 or fewer comorbidities. Five patients required replacement with a Jackson tracheostomy tube due to persistent tracheostomal granulation tissue (n = 2), feeling safer with the tracheostomy tube (n = 1), a posterior scar band causing airway obstruction (n = 1), and inability to care for the cannula because of poor manual dexterity from arthritis (n = 1). The mean (range) body mass index of successful and unsuccessful users was 27.5 (18.2-37.7) and 33.8 (24.1-42.7), respectively. Complications included the cannula being blocked by adipose tissue (n = 2) or pushed posteriorly into the airway (n = 2). The Montgomery cannula was used as a successful decannulation tool in 4 patients-with the cannula serving as an interim airway management tool leading to tracheostome closure. We identified features associated with successful use of the cannula and an additional indication for a Montgomery cannula as a step-down management tool for decannulation.


Neural substrates of social emotion regulation: a FMRI study on imitation and expressive suppression to dynamic facial signals.
Emotion regulation is crucial for successfully engaging in social interactions. Yet, little is known about the neural mechanisms controlling behavioral responses to emotional expressions perceived in the face of other people, which constitute a key element of interpersonal communication. Here, we investigated brain systems involved in social emotion perception and regulation, using functional magnetic resonance imaging (fMRI) in 20 healthy participants. The latter saw dynamic facial expressions of either happiness or sadness, and were asked to either imitate the expression or to suppress any expression on their own face (in addition to a gender judgment control task). fMRI results revealed higher activity in regions associated with emotion (e.g., the insula), motor function (e.g., motor cortex), and theory of mind (e.g., [pre]cuneus) during imitation. Activity in dorsal cingulate cortex was also increased during imitation, possibly reflecting greater action monitoring or conflict with own feeling states. In addition, premotor regions were more strongly activated during both imitation and suppression, suggesting a recruitment of motor control for both the production and inhibition of emotion expressions. Expressive suppression (eSUP) produced increases in dorsolateral and lateral prefrontal cortex typically related to cognitive control. These results suggest that voluntary imitation and eSUP modulate brain responses to emotional signals perceived from faces, by up- and down-regulating activity in distributed subcortical and cortical networks that are particularly involved in emotion, action monitoring, and cognitive control.


[Study on the acid hydrolysis, fiber remodeling and bionics mineralization of rat tail tendon collagen type Ⅰ].
Objective: To produce bionic bone material that is consistent with human bone in chemical composition and molecular structure using rat tail tendon collagen type Ⅰ. Methods: The type Ⅰcollagen derived from rat tail was extracted by acetic acid to form collagen fibers. The reconstructed collagen fibers were placed in the mineralized solution to mimic bone mineralization for 2-6 days. Bone mineralization was observed by transmission electron microscopy and electron diffraction.Results: Collagen fibers with characteristic D-Band structure were reconstructed by using rat tail tendon collagen type Ⅰ extracted with acid hydrolysis method. Transmission electron microscopy and electron diffraction showed that calcium hydroxyapatite precursor infiltrated into the collagen fibers, and the collagen fibers were partially mineralized after 2 days of mineralization; the collagen fibers were completely mineralized and bionic bone material of typeⅠ collagen/calcium hydroxyapatite was formed after 6 days of mineralization.Conclusion: The collagen type Ⅰ can be extracted from rat tail tendon by acid hydrolysis method, and can be reformed and mineralized to form the bionic bone material which mimics human bone in chemical composition and the molecular structure.


Inflammatory myofibroblastic tumour: report of a rare form with exclusive pleural involvement.
Inflammatory myofibroblastic tumour (IMT) is a rare scleroinflammatory lesion, characterized by a myofibroblastic proliferation with inflammatory infiltrates, with many possible locations and diagnosis based on immunohistochemistry. Pleural IMT is uncommon and is usually an extension of a pulmonary involvement. We report on a 28-year-old woman with a new form of this rare entity, characterized by exclusive pleural involvement.


Transition from sea to land: olfactory function and constraints in the terrestrial hermit crab Coenobita clypeatus.
The ability to identify chemical cues in the environment is essential to most animals. Apart from marine larval stages, anomuran land hermit crabs (Coenobita) have evolved different degrees of terrestriality, and thus represent an excellent opportunity to investigate adaptations of the olfactory system needed for a successful transition from aquatic to terrestrial life. Although superb processing capacities of the central olfactory system have been indicated in Coenobita and their olfactory system evidently is functional on land, virtually nothing was known about what type of odourants are detected. Here, we used electroantennogram (EAG) recordings in Coenobita clypeatus and established the olfactory response spectrum. Interestingly, different chemical groups elicited EAG responses of opposite polarity, which also appeared for Coenobita compressus and the closely related marine hermit crab Pagurus bernhardus. Furthermore, in a two-choice bioassay with C. clypeatus, we found that water vapour was critical for natural and synthetic odourants to induce attraction or repulsion. Strikingly, also the physiological response was found much greater at higher humidity in C. clypeatus, whereas no such effect appeared in the terrestrial vinegar fly Drosophila melanogaster. In conclusion, our results reveal that the Coenobita olfactory system is restricted to a limited number of water-soluble odourants, and that high humidity is most critical for its function.


Symptomatic versus asymptomatic patients in congenital hypoplasminogenemia: a statistical analysis.
In the present study, the prevalence of thromboembolic events in patients suffering from type I plasminogen deficiency was evaluated. One hundred and twelve affected subjects belonging to twenty-eight kindreds were gathered from the literature and from personal observations. The incidence of thrombosis found in this group was compared with those seen in: a) 86 unaffected family members; b) 100 hospitalized patients; c) 100 outpatient clinic patients. In the latter two groups, congenital clotting disorders were excluded. Thrombotic manifestations were found in 25.8% of patients with plasminogen deficiency, a figure which was statistically different from those found in unaffected family members (1.16%, p < 0.001), hospitalized patients (3%, p < 0.001) and outpatient clinic patients (5%, p < 0.001). In twenty-four kindreds with hypoplasminogenemia, data concerning the actuarial ages at first thrombotic event were available for construction of thrombosis-free survival curves by the Cutler-Ederer method. The difference between the two curves, corresponding to affected and unaffected family members respectively, were statistically significant (p < 0.01). In conclusion, although the incidence of thromboembolic events in type I plasminogen deficiency is certainly lower than that described in other congenital clotting disorders such as AT III, protein C and protein S, patients with hypoplasminogenemia should be considered at risk for thrombosis, particularly when triggering factors are present.


Cyclosporin-associated microfibrils in cardiac transplant patients.
Endomyocardial biopsies from 21 cyclosporin-treated cardiac transplant patients were studied at the ultrastructural level. Eight patients exhibited focal interstitial accumulation of filaments, which most commonly measured 8-10 nm in diameter (range 7-16 nm). The filaments were straight, hollow, and nonbranching. Filament accumulation was observed as early as 4 days posttransplant. No filament accumulation was observed in 17 donor endomyocardial biopsies obtained at the time of transplantation. The ultrastructure of the filaments was similar to that of amyloid fibrils. Stains for amyloid at the light microscopic level were uniformly negative, however. Until the exact nature of the filaments is determined, we propose that they be referred to as cyclosporin associated microfibrils.


A cytotoxicity study of fluorescent carbon nanodots using human bronchial epithelial cells.
The labeling of living cells with carbon nanoparticles has been increasingly studied both in vivo and in vitro, but concerns about the potential cytotoxicity of these nanoprobes are also increasing. In this study, the fluorescent carbon dots (CDs) without surface modification was synthesized and evaluated for its cytotoxicity. Indicators including cell viability, total reactive oxygen species (ROS), glutathione, malondialdehyde and lactate dehydrogenase were assessed using human bronchial epithelial (16HBE) cell line. Our results showed that CDs preferred to locate on the surface of cells, which significantly increased the membrane permeability of 16HBE cells. CDs exposure could further induce oxidative stress, exhaust the antioxidant defenses of cells and finally lead to decreased cell viability. Therefore, surface modification of CDs is needed to minimize its cytotoxicity. The present work is useful for the development of new strategies towards the in vitro and in vivo applications of CDs for optical imaging and drug delivery.


Systemic lupus erythematosus in pregnancy: high risk, high reward.
The aim of this study was to describe risks of systemic lupus erythematosus (SLE) in pregnancy and the importance of preconception counselling, medication optimization and close surveillance. Advances in care for pregnant patients with SLE have led to improved obstetric outcomes, but maternal and foetal risks continue to be elevated. Conception during periods of disease quiescence and continuation of most medications decrease adverse pregnancy outcomes. Hydroxychloroquine (HCQ) appears protective against flares in pregnancy, neonatal congenital heart block and preterm birth. SLE in pregnancy confers increased maternal and foetal risks, including disease flares, preeclampsia, preterm birth, foetal growth restriction, neonatal lupus erythematosus (NLE) and congenital heart block. Disease control on an effective medication regimen mitigates many of these risks, but pregnancy in women with SLE remains a high-risk condition requiring multidisciplinary care and an individualized approach to each patient.


Step-rate thresholds for physical activity intensity in persons with multiple sclerosis.
This study examined whether the relationship between metabolic equivalent units (METs) and step-rate is altered in persons with multiple sclerosis (MS) and developed step-rate thresholds for activity intensity for these persons. Participants were 24 persons with MS (20 women; age = 44 ± 12) and 24 healthy persons without MS (20 women; age = 41 ± 11). The MS group was divided using the 12-item MS Walking Scale (MSWS-12) into two walking impairment subgroups: (a) minimal (n = 13, MSWS-12 ≤ 12.5) and (b) mild-moderate (n = 11, MSWS-12 > 12.5). METs were measured with spirometry and step-rate with hand-tally. Step-rate, height, group, the step-rate by group interaction, and the square of step-rate significantly predicted METs. At a given height, the step-rate thresholds at 3 and 6 METs were lower for persons with minimal impairment than persons without MS and even lower for persons with mild-moderate impairment. The relationship between METs and step-rate is altered in persons with MS, lowering their step-rate thresholds for activity intensity, especially for persons with MS who have higher levels of walking impairment.


[Long-term oxygen therapy--impact on the quality of life in persons with chronic obstructive lung disease].
Chronic bronchopenumopathies are today a real public health problem. They are mainly due to tobacco, and during their development, they generate a heavy handicap. At an advanced stage, the patient develops a respiratory insufficiency and then requires a substitution treatment: long lasting oxygen therapy. The study we have just carried out shows that such a treatment enabling to prolong life is not totally justified as an improvement of life quality. Indeed, it seems to aggravate the constraints engendered by the disease itself. A training on the place of prescription, the development of hospital-home care service networks and patients associations, would perhaps allow a better acceptance and adaptation to the treatment (these suggestions could be the subject of future research). Likewise, it might be interesting to ponder over the impact of making the general public and the smokers sensitive to such a condition and to the handicap it generates.


Endovenous obliteration versus conventional stripping operation in the treatment of primary varicose veins: a randomized controlled trial with comparison of the costs.
The aim of this randomized study was to compare a new method of endovenous saphenous vein obliteration (Closure System, VNUS Medical Technologies, Inc, Sunnyvale, Calif) with the conventional stripping operation in terms of short-term recovery and costs. Twenty-eight selected patients for operative treatment of primary greater saphenous vein tributary varicose veins were randomly assigned to endovenous obliteration (n = 15) or stripping operation (n = 13). Postoperative pain was daily assessed during the 1st week and on the 14th postoperative day. The length of sick leave was determined. The RAND-36 health survey was used to assess the patient health-related quality of life. The patient conditions were controlled 7 to 8 weeks after surgery, and patients underwent examination with duplex ultrasonography. The comparison of costs included both direct medical costs and costs resulting from lost of productivity of the patients. Costs that were similar in the study groups were not considered in the analysis. All operations were successful, and the complication rates were similar in the two groups. Postoperative average pain was significantly less severe in the endovenous obliteration group as compared with the stripping group (at rest: 0.7, standard deviation [SD] 0.5, versus 1.7, SD 1.3, P =.017; on standing: 1.3, SD 0.7, versus 2.6, SD 1.9, P =.026; on walking: 1.8, SD 0.8, versus 3.0, SD 1.8, P =.036; with t test). The sick leaves were significantly shorter in the endovenous obliteration group (6.5 days, SD 3.3 days, versus 15.6 days, SD 6.0 days; 95% CI, 5.4 to 12.9; P <.001, with t test). Physical function was also restored faster in the endovenous obliteration group. The estimated annual investment costs of the closure operation were US $3360. The other direct medical costs of the Closure operation were about $850, and those of the conventional treatment were $360. With inclusion of the value of the lost working days, the Closure treatment was cost-saving for society, and when 40% of the patients are retired (or 60% of the productivity loss was included), the Closure procedure became cost-saving at a level of 43 operations per year. Endovenous obliteration may offer advantages over the conventional stripping operation in terms of reduced postoperative pain, shorter sick leaves, and faster return to normal activities, and it appears to be cost-saving for society, especially among employed patients. Because the procedure is also associated with shorter convalescence, this new method may potentially replace conventional varicose vein surgery.


The effect of X-irradiation upon the fate of cancellous bone allografts in inbred rats.
The effect of two doses of X-irradiation upon the osteogenesis in isografts or allografts of cancellous bone has been studied. Exposure of rats to 500 rads of X-irradiation caused a transient depression in osteogenesis in the skeleton. This depression was more marked, however, after 600 rads of X-ray. Five hundred rads of X-ray had no effect upon the level of osteogenesis in isografts 2 weeks after grafting, but did depress new bone formation in 3-week-old grafts. The higher dose of X-rays caused a more profound depression in new bone formation at both 2 and 3 weeks. Both 500 rads and 600 rads of X-ray had little effect upon the degree of first phase osteogenesis in H-1 disparate allografts. However, there was some improvement in late phase new bone formation in recipients treated with 600 rads. Both doses of X-rays markedly improved the amount of first phase osteogenesis in H-1 identical allografts. There was also a significant improvement in the new bone formation in grafts in the second phase. The significance of these findings is discussed.


Self-reported syphilis and gonorrhoea testing among men who have sex with men: national HIV behavioural surveillance system, 2003-5.
The Centers for Disease Control and Prevention provides guidance on sexually transmitted disease (STD) testing specifically for men who have sex with men (MSM) in STD treatment guidelines to address increasing rates of gonorrhoea and syphilis among MSM in the USA. The guidelines recommend at least annual syphilis, gonorrhoea and chlamydia testing for sexually active MSM. The implementation of these guidelines was evaluated. Data from the 2003-5 MSM cycle of the National HIV Behavioural Surveillance System were used. The proportion of sexually active HIV-negative MSM reporting syphilis and gonorrhoea testing during the previous year was determined and multivariate logistic regression was used to identify factors associated with testing. Of 10 030 MSM, 39% and 36% reported having been tested for syphilis and gonorrhoea in the previous year, respectively. Four factors were associated with syphilis and gonorrhoea testing, respectively: age 18-24 years versus > or =45 years (odds ratio (OR) 2.2, 95% CI 1.8 to 2.5; OR 2.7, 95% CI 2.3 to 3.2), black versus white race (OR 1.3, 95% CI 1.1 to 1.4; OR 1.4, 95% CI 1.2 to 1.6), private insurance versus no insurance (OR 1.3, 95% CI 1.1 to 1.4; OR 1.3, 95% CI 1.1 to 1.4) and disclosing male-male sex to a healthcare provider (OR 2.2, 95% CI 2.0 to 2.5; OR 2.1, 95% CI 1.9 to 2.3). Syphilis and gonorrhoea testing among MSM was low, despite specific testing recommendations in the STD treatment guidelines. To increase STD testing among MSM, healthcare providers should assess the risks of STD for male patients through routine enquiries about sexual activity.


Artificial seawater based long-term culture of colonial ascidians.
Tunicates are highly diverse marine invertebrate filter-feeders that are vertebrates' closest relatives. These organisms, despite a drastically different body plan during their adulthood, have a tissue complexity related to that of vertebrates. Ascidians, which compose most of the Tunicata, are benthic sessile hermaphrodites that reproduce sexually through a motile tadpole larval stage. Over half of the known ascidians species are able to reproduce asexually by budding, typically leading to the formation of colonies where animals, called zooids, are interconnected through an external vascular system. In addition, colonial ascidians are established models for important biological processes including allorecognition, immunobiology, aging, angiogenesis and whole-body regeneration. However, the current paucity in breeding infrastructures limits the study of these animals to coastal regions. To promote a wider scientific spreading and popularity of colonial ascidians, we have developed a flexible recirculating husbandry setup for their long-term in-lab culture. Our system is inspired both by the flow-through aquariums used by coastal ascidian labs, as well as by the recirculating in-lab systems used for zebrafish research. Our hybrid system thus combines colony breeding, water filtering and food culturing in a semi-automated system where specimens develop on hanging microscopy glass slides. Temperature, light/dark cycles, flow speed and feeding rates can be controlled independently in four different breeding environments to provide room for species-specific optimization as well as for running experiments. This setup is complemented with a quarantine for the acclimatization of wild isolates. Herein we present our success in breeding Botrylloides diegensis, a species of colonial ascidians, for more than 3 years in recirculating artificial seawater over 600 km away from their natural habitat. We show that colonies adapt well to in-lab culturing provided that a suitable marine microbiome is present, and that a specific strain can be isolated, propagated and efficiently used for research over prolonged periods of time. The flexible and modular structure of our system can be scaled and adapted to the needs of specific species, such as Botryllus schlosseri, as well as of particular laboratory spaces. Overall, we show that Botrylloides diegensis can be proficiently bred in-land and suggest that our results can be extended to other species of colonial ascidians to promote research on these fascinating animals.


High altitude agriculture in the Titicaca basin (800 BCE-200 CE): Impacts on nutrition and disease load.
This study investigates the biological impacts of sedentism and agriculture on humans living in the high altitude landscape of the Titicaca Basin between 800 BCE and CE 200. The transition to agriculture in other global areas resulted in increases in disease and malnutrition; the high altitude of the Titicaca Basin could have exacerbated this. Our objective is to test whether the high altitude of the Titicaca Basin created a marginal environment for early agriculturalists living there, reflected through elevated rates of malnutrition and/or disease. To test this, we analyzed human remains excavated from seven archaeological sites on the Copacabana Peninsula for markers of diet and disease. These markers included dental caries, dental abscesses, cribra orbitalia, porotic hyperostosis, periosteal reactions, osteomyelitis, and linear enamel hypoplasia. Results showed that markers of diet did not support malnutrition or micronutrient deficiencies but instead, indicated a relatively diverse diet for all individuals. Markers of disease also did not vary significantly but were common, indicating circulation of pathogens or chronic bodily stress. We interpret these results as an indication that while diets remained nutritious, investment in the landscape exposed populations to issues of sanitation and disease. The high-altitude of the Titicaca Basin did not exacerbate the biological impacts of agriculture in terms of increased malnutrition. Additionally, disease load was likely related to problems faced by many sedentary groups as opposed to unique challenges posed by high altitude. In sum, despite the high elevation, the Titicaca Basin is not truly a marginal environment for humans.


The Intergenerational Transmission of Suicide: Moral Injury and the Mysterious Object in the Work of Walker Percy.
The intrapsychic mechanisms for the intergenerational transmission of suicide are not adequately theorized, though it is well known that a family history of suicide places survivors at increased risk for suicide. The suicide of a family member, particularly a parent, it is hypothesized, marks some survivors with a type of trauma associated with moral injury, which may produce an alteration in object relations with the emergence of what may be called a mysterious object. Under the press of these conditions, survivors may embark on what Apprey (2014) has termed an "urgent errand" in an effort to solve a problem in the anterior generation. Analysands with a history of familial suicide may bring symptoms of moral injury, a mysterious object relation, and a risk for suicide into the transference. The family history, life history, and literary work of the novelist Walker Percy, who had an extensive family history of suicide, provides evidence for the hypothesis linking moral injury, a mysterious object, and an urgent errand in such patients.


Cognition and depression: the effects of fluvoxamine, a sigma-1 receptor agonist, reconsidered.
Cognitive impairment is a primary feature of patients with major depressive disorder (MDD) and is characterised by stress-induced neural atrophy. Via alpha-adrenergic, anti-cholinergic and anti-histaminic activities, several antidepressants can cause significant counter-therapeutic cognitive impairment. Evidence is emerging of the involvement of sigma-1 receptor agonism in the mechanism of action of some antidepressants, notably fluvoxamine. Sigma-1 receptors are abundant in areas affected by depression/stress-induced cerebral atrophy and their ligands have a unique pharmacological profile; they may promote neurogenesis and initiate adaptive neural plasticity as a protection/reaction to stress. Fluvoxamine, as a potent sigma-1 receptor agonist, has shown ameliorating effects in animal models of psychosis, depression, stress, anxiety, obsessive-compulsive disorder (OCD) and aggression and has been shown to improve cognitive impairments. In humans, fluvoxamine may repair central nervous system (CNS) atrophy and restore cognitive function. The current review explores the mechanisms through which sigma-1 receptors can modulate cognitive function and examines how antidepressant therapy with fluvoxamine may help improve cognitive outcomes in patients with depression.


Influence of type and opsonization of ingested particle on intracellular free calcium distribution and superoxide production by human neutrophils.
Intracellular free calcium concentration [( Ca2+]i) was measured with the fluorescent Ca2+ indicator Fura 2 within individual human neutrophils during the phagocytosis of several types of particles, including serum-treated zymosan (STZ), immunoglobulin G (IgG)-coated zymosan (IGZ), C3b-coated zymosan (C3Z), nontreated zymosan (Z), and serum-treated similarly sized latex particles (STL). STZ was coated with both IgG and C3b. IGZ was coated with only IgG, and C3Z was coated with only C3b. STL was coated with only C3b but to a lesser extent than C3Z. The ingestion of particles was greatest for STZ and somewhat lower for C3Z. Ingestion of IGZ and STL was much less than ingestion of C3Z. The relative efficiencies of the particles for inducing superoxide production were as follows: STZ greater than IGZ = C3Z greater than Z = STL. [Ca2+]i significantly increased from the resting level of approximately 70 to greater than 240 nM (P less than 0.01) during phagocytosis of the particles. The increment in [Ca2+]i was greater in the paraphagosomal region than in the cell body after the ingestion of STZ or IGZ. The mean peak [Ca2+]i values in the paraphagosomal cytoplasm of neutrophils ingesting one particle of STZ, IGZ, C3Z, Z and STL were 536.1 +/- 57.6, 424.7 +/- 55.8, 373.8 +/- 62.7, 272.3 +/- 31.5, and 270.8 +/- 38.0 nM, respectively, which showed good correlation (r = 0.97) with the efficiency of the particles for inducing superoxide production. Depletion of extracellular Ca2+ by EGTA [ethylene glycol-bis(beta-aminoethyl ether)-N,N,N'N'-tetraacetic acid] attenuated both [Ca2+]i increase and superoxide production induced by particles. Thus [Ca2+]i increased after ingestion of several types of particles, and the subcellular pattern of [Ca2+]i was different depending on the type of particle ingested. Greater increases in paraphagosomal [Ca2+]i were closely associated with greater increases in superoxide production by neutrophils.


Effects of antioxidants on surfactant peroxidation by stimulated human polymorphonuclear leukocytes.
Production of oxygen radicals by stimulated phagocytes followed by surfactant lipid peroxidation (LPO) and loss of surfactant function have all been implicated in the pathogenesis of acute lung injury. We studied the interactions between natural lung surfactant (Curosurf) and neutrophils in vitro, and compared various antioxidants; (superoxide dismutase (SOD), vitamin E, vitamin C, ebselen and melatonin), or combinations of them in duplicate and triplicate regarding their ability to decrease superoxide production and the peroxidation level of surfactant caused by activated phagocytes. The superoxide production of neutrophils activated by Candida albicans was measured with the nitroblue tetrazolium (NBT) test. The subsequent LPO was estimated as the content of malondialdehyde (MDA) and 4-hydroxyalkenals (4-HNE). We found that lung surfactant decreased the superoxide production by activated neutrophils (29.7%) and that Curosurf was peroxidized with elevated MDA/4-HNE values. With supplements of antioxidants (except vitamin C), superoxide radical production and the surfactant LPO level fell in a dose-dependent manner. The protective effect of the antioxidants differed in each test. SOD had a slight effect in both tests. The findings with vitamin E, melatonin and ebselen were similar. The best combination was that of a natural and a synthetic antioxidant (melatonin-ebselen) with a 60% decrease in comparison to the corresponding control. These findings suggest that antioxidants, particularly in combination, prevent LPO of lung surfactant.


Role of diffusion tensor imaging or magnetic resonance spectroscopy in the diagnosis and disability assessment of amyotrophic lateral sclerosis.
To compare the results of magnetic resonance spectroscopy (MRS) and diffusion tensor imaging (DTI) in amyotrophic lateral sclerosis (ALS) patients. Nineteen ALS patients and thirteen age-matched healthy controls underwent MRS and DTI between October 2013 and July 2014. Fractional anisotropy (FA), apparent diffusion coefficient (ADC), N-acetylaspartate (NAA), choline (Cho), and creatine (Cr) were collected as the quantitative results of the imaging study. The ALS functional rating scale-revised (ALSFRS-R) and disease progression rate were evaluated to assess patients' disability. The imaging study results were compared between ALS patients and healthy controls. The relationship between disability assessment and imaging study results was analyzed. NAA/Cr in the motor cortex and FA in the corticospinal tract (CST) of both sides were significantly lower in patients than controls. There was no significant difference between the two groups in Cho/Cr, tract length, tract volume, ADC or NAA. No relationship was found between ALSFRS-R and FA (r=0.243, p=0.316) in the right CST; NAA (r=0.095, p=0.699) or NAA/Cr (r=0.172, p=0.481) in the left motor cortex; or NAA (r=0.320, p=0.182) or NAA/Cr (r=0.193, p=0.492) in the right motor cortex. There was no relationship between the disease progression rate and FA, NAA, or NAA/Cr on either side. NAA/Cr and FA can help diagnose ALS. Regional brain NAA/Cr and FA values could not assess the ALSFRS-R or disease progression rate.


Acoustic correlates of plosive voicing in Madurese.
Madurese, a Malayo-Polynesian language of Indonesia, is of interest both areally and typologically: it is described as having a three-way laryngeal contrast between voiced, voiceless unaspirated, and voiceless aspirated plosives, along with a strict phonotactic restriction on consonant voicing-vowel height sequences. An acoustic analysis of Madurese consonants and vowels obtained from the recordings of 15 speakers is presented to assess whether its voiced and aspirated plosives might share acoustic properties indicative of a shared articulatory gesture. Although voiced and voiceless aspirated plosives in word-initial position pattern together in terms of several spectral balance measures, these are most likely due to the following vowel quality, rather than aspects of a shared laryngeal configuration. Conversely, the voiceless (aspirated and unaspirated) plosives share multiple acoustic properties, including F0 trajectories and overlapping voicing lag time distributions, suggesting that they share a glottal aperture target. The implications of these findings for the typology of laryngeal contrasts and the historical evolution of the Madurese consonant-vowel co-occurrence restriction are discussed.


Assessment of the proliferation status of glioblastoma cell and tumour tissue after nanoplatinum treatment.
Glioblastoma is one of the most frequent primary brain tumours of the central nervous system, with a poor survival time. With inefficient chemotherapy, it is urgent to develop new strategies for tumour therapy. The present approach is based on the inhibition of cell proliferation using platinum nanoparticles (NP-Pt). The aim of the study was to evaluate and compare the antiproliferative properties of NP-Pt and cisplatin against U87 and U118 glioma cell lines and U87 tumour tissue. NP-Pt and cisplatin were incubated with U87 and U118 glioma cells or administered directly into glioma tumour tissue. Cell morphology, the level of DNA synthesis, the migration of cells, protein expression levels of proliferating cell nuclear antigen (PCNA) and the level of DNA oxidation in glioma tumours were investigated. The results showed that NP-Pt treatment of U87 and U118 glioma cells decreased the level of DNA synthesis and the migration of cancer cells but also downregulated the level of PCNA protein expression in tumour tissue. Furthermore, NP-Pt caused oxidative DNA damage in tumour tissue to a higher degree than cisplatin. Consequently, NP-Pt can be considered as an effective inhibitor of glioblastoma tumour cell proliferation. However, the mechanism of action and potential side effects need to be elucidated further.


[Study on the epidemiological characteristics and natural infectious focus of Angiostrongylus cantonensis in Shenzhen area of Zhujiang Delta in China].
To delimit the natural infectious focus, including the distribution of wildlife, species, ecology of intermediate hosts and final host of Angiostrongylus cantonensis, as well as the routes of transmission and epidemiological characteristics and wildlife of human Angiostrongylus cantonensis, based on human diverging cases identified in Shenzhen, southern area of China. Data including rate of infection and density of Angiostrongylus cantonensis among different hosts in 12 different areas in Shenzhen was collected, using microscope to inspect homogenate liquids of snails. Wild mice were captured with mouse cage to examine the adult Angiostrongylus cantonensis. Using larva isolated from wild-snails-infected rats to observe the life cycle of Angiostrongylus cantonensis. Wild life of Angiostrongylus cantonensis existed in the southwest part of Shenzhen with its majority intermediate hosts as Achatina fulica. The overall rate of infection was 31% in wildlife and final host was found to be Rattus andersoni, Achatina fulica which were extensively distributed in the shrub region of Shenzhen because of suitable climate, humidity and vegetation for generating the life cycle of Achatina fulica. Human infected Angiostrongylus cantonensis was mainly due to eating raw snails or vegetables contaminated by larva of Angiostrongylus cantonensis. The peak of infection was seen from April to November in Shenzhen area. Wildlife of Angiostrongylus cantonensis existed in the southwest part of Shenzhen with major wildlife reservoir including fresh water snail and wild mouse. The existence of natural focus Angiostrongylus cantonensis was now recognized as an important source of human angiostrongyliasis in Shenzhen area.


Humeral Torsion as a Risk Factor for Shoulder and Elbow Injury in Professional Baseball Pitchers.
Numerous studies have demonstrated that humeral retrotorsion is increased in the dominant arms of throwing athletes. No study has clearly defined the relationship between humeral retrotorsion and shoulder and elbow injury. Uninjured professional pitchers will display more dominant humeral torsion (HT) than professional pitchers who sustain shoulder injuries but less than pitchers who sustain elbow injuries. Case-control study; Level of evidence, 3. Pitchers from the Colorado Rockies professional baseball organization were recruited for participation for this prospective injury study from 2009 to 2013. HT was assessed using indirect ultrasonographic techniques and was measured prospectively in 255 pitchers before each spring training (average of 2 trials). From the beginning of the preseason to the end of the postseason, overuse upper extremity injuries (shoulder or elbow) were tracked for each participating athlete. All athletes who reported pain or injury to their coach were referred to the organization's athletic trainer for evaluation and classification of each injury. The difference in HT was calculated by subtracting measurement of the dominant arm from the nondominant arm, and 3 separate mixed-model analyses of variance (side × injury group) were used to compare the dominant and nondominant HT between all pitchers who developed an arm injury (shoulder and elbow combined), as well as comparing pitchers who developed a shoulder or elbow injury to those who did not miss games due to shoulder or elbow injury (α = .05). During the course of the study, 60 arm (30 shoulder; 30 elbow) injuries were observed; 195 pitchers did not suffer an injury. There were no differences when HT was compared between all injured (shoulder and elbow injuries combined) and uninjured pitchers (P = .13; effect size 0.14). There was a significant interaction effect showing that pitchers who suffered a shoulder injury displayed 4° less dominant humeral retrotorsion compared with pitchers without injury (P = .04) and that pitchers with elbow injury displayed 5° greater humeral retrotorsion (P = .04). In addition, those who suffered an ulnar collateral ligament injury requiring reconstruction (n = 17) also displayed 4(o) greater dominant retrotorsion and 5° less nondominant humeral retrotorsion compared with pitchers who did not suffer an injury (n = 195; P = .05). There was not a significant difference between nondominant HT among pitchers who sustained shoulder and elbow injuries and pitchers without injury. The results of this study show a contrast in dominant humeral retrotorsion between pitchers who suffered shoulder and elbow injuries compared with those without an injury. Pitchers who sustained shoulder injuries had less dominant humeral retrotorsion compared with noninjured pitchers. In contrast, pitchers who sustained time-loss elbow injuries displayed increased humeral retrotorsion compared with noninjured pitchers. Together, these results suggest that increased adaptive humeral retrotorsion is protective against shoulder injuries but a harmful contributor for elbow injuries in professional pitchers. This is the first study to show differing injury risk profiles for shoulder and elbow injury.


Evidence for a novel late-onset Alzheimer disease locus on chromosome 19p13.2.
Late-onset familial Alzheimer disease (LOFAD) is a genetically heterogeneous and complex disease for which only one locus, APOE, has been definitively identified. Difficulties in identifying additional loci are likely to stem from inadequate linkage analysis methods. Nonparametric methods suffer from low power because of limited use of the data, and traditional parametric methods suffer from limitations in the complexity of the genetic model that can be feasibly used in analysis. Alternative methods that have recently been developed include Bayesian Markov chain-Monte Carlo methods. These methods allow multipoint linkage analysis under oligogenic trait models in pedigrees of arbitrary size; at the same time, they allow for inclusion of covariates in the analysis. We applied this approach to an analysis of LOFAD on five chromosomes with previous reports of linkage. We identified strong evidence of a second LOFAD gene on chromosome 19p13.2, which is distinct from APOE on 19q. We also obtained weak evidence of linkage to chromosome 10 at the same location as a previous report of linkage but found no evidence for linkage of LOFAD age-at-onset loci to chromosomes 9, 12, or 21.


Amino Nitrogen Quantum Dots-Based Nanoprobe for Fluorescence Detection and Imaging of Cysteine in Biological Samples.
Fluorescent amino nitrogen quantum dots (aN-dots) were synthesized by microwave-assisted method using 2-azidoimidazole and aqueous ammonia. The aN-dots have a nitrogen component up to 40%, which exhibit high fluorescence quantum yield, good photostability, and excellent biocompatibility. We further explored the use of the aN-dots combined with AuNPs as a nanoprobe for detecting fluorescently and imaging of cysteine (Cys) in complex biological samples. In this sensing system, the fluorescence of aN-dots was quenched significantly by gold nanoparticles (AuNPs), while the addition of Cys can lead to the fluorescence signal recovery. Furthermore, we have demonstrated that this strategy can offer a rapid and selective detection of Cys with a good linear relationship in the range of 0.3-3.0 μmol/L. As expected, this assay was successfully applied to the detection of Cys in human serum and plasma samples with recoveries ranging from 90.0% to 106.7%. Especially, the nanoprobe exhibits good cell membrane permeability and excellent biocompatibility by CCK-8 assay, which is favorable for bioimaging applications. Therefore, this fluorescent probe ensemble was further used for imaging of Cys in living cells, which suggests our proposed method has strong potential for clinical diagnosis. As a novel member of the quantum-dot family, the aN-dots hold great promise to broaden applications in biological systems.


Central and peripheral nervous system involvement in neuromelioidosis.
We report a case of a 33-year-old Sri Lankan man who presented with flaccid quadriparesis with brainstem signs and acute motor axonal polyneuropathy. MRI of the brain showed multiple abscesses with ring enhancement seen predominantly in the brainstem and upper cervical cord. The patient was initially treated with intravenous immunoglobulin, considering this to be a form of Guillain-Barré syndrome. Cerebrospinal fluid, however, showed lymphocytic pleocytosis with raised protein. Tests for Brucella, tuberculosis, toxoplasmosis, syphilis and HIV were negative. Chest X-ray revealed a cavity in the left lung, which, on bronchoscopy, showed a collection of purulent secretions. Culture of these secretions grew Burkholderia pseudomallei. The patient was treated with two courses of intravenous antibiotics, with resultant radiological improvement; however, with significant morbidity.


Role of early contrast enhanced CT scan in severity prediction of acute pancreatitis.
Severe pancreatitis occurs in approximately 15-25% of patients with acute pancreatitis. The objective of our study was to compare the CT Severity Index (CTSI) with a clinical score (BISAP score) to predict severity of acute pancreatitis. Forty-eight consecutive patients with acute pancreatitis who underwent contrast enhanced CT scan within 72 hours of presentation were included. Results of our study showed that both CTSI and BISAP score were reliable predictors of mortality (p value = 0.019 and <0.001 respectively) and need for mechanical ventilation (p value = .002 and .006 respectively). Positive predictive value of CTSI to predict recovery without intervention was 91.4% as compared to 78% for that of BISAP score. Receiver Operating Characteristics (ROC) Curves showed CT scan was superior to BISAP Score in predicting need of percutaneous or surgical intervention. Early CT scan may be utilized for prediction of clinical course of patients with acute pancreatitis.


It's transformation, not patient care!
Patient care isn't just about performing technical tasks. While that is a large and absolutely essential part of nursing care, the essence of care is helping patients and their families transform their lives into a healthful experience even though the essence may be a devastating diagnoses or a worsening illness. If we believe that patients are merely buying the technical skills of the nurse, we are in for a grievous disappointment. People today want to develop their intellectual assets and develop their souls at work. If the workplace can't help with this search, both patients and employees will find one that will. Patients want the opportunity to grow and transform their lives. And so do our staff. They will learn from leaders who are providing the role models and the environment for this to happen.


Environmental friendly utilization of plant wastes in combination as a source of natural colorants for binary mordanted silk dyeing.
This study investigates the absorption behavior of natural dyes on silk fabric: madder roots (red dye) and amaltas (brown dye). The dyes were extracted under optimized conditions in an acidic medium. Binary mixtures of these dyes in different proportions were employed to develop various shades. This research work has explored the impact of single as well as binary mixture of chemical mordants on the dyeing behavior of natural dyes on silk. Al (Alum), iron (Fe), and tannic acid (T.A.) were used as pre- and post-mordants. Different concentrations of the dye mixtures were used to achieve different shades. The absorption behavior of the binary mixture of natural dyes was assessed using a spectra photometer Colori-spectra SF600. The study found that the highest color strength was achieved when an acidic extract with a table salt concentration of 2 g/100 mL was applied to silk fabric at 65 °C for 55 min and subjected to microwave treatment for 6 min. The study revealed excellent results for the selected binary mixtures of chemical mordants, such as (Al + Fe), (Al + T.A.), and (Fe + T.A.), in comparison by employing single mordants such as (Al, Fe, and T.A.).