Differential KIT expression in histological subtypes of adenoid cystic carcinoma (ACC) of the salivary gland.
Adenoid cystic carcinoma (ACC) of the salivary gland is characterized by a prolonged but inevitably unfavorable clinical course. Recent studies suggested the transmembrane tyrosine kinase KIT to be involved in ACC pathogenesis. To investigate KIT expression in histologically defined subgroups of ACC and to clarify whether KIT gene copy number gain contributes to KIT overexpression, tumor tissue microarray sections including 55 ACC tumors were analyzed by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). The prevalence of positive KIT immunostaining was 89% (49/55). Strong immunostaining of KIT was only found in cribriform and tubular but never in solid subtypes (p=0.02). Average KIT staining intensity was higher in cribriform and tubular (n=37) compared to solid (n=18) ACC subtypes (p=0.005). FISH analysis revealed copy number gains of the KIT gene in 6.1% (3/49) of tumors analyzed. Our results implicate that specific KIT tyrosine kinase inhibitors such as imatinib, might be used in future therapeutic approaches against subgroups of ACC.


Thermostabilization of Bacillus subtilis GH11 xylanase by surface charge engineering.
Aiming to improve thermostability of the mesophilic xylanase A from Bacillus subtilis (XynA), five single mutants (S22E, S27E, N32D, N54E and N181R) were used to construct a random combinatorial library, and screening of this library for thermostable XynA variants identified a double mutant (S22E/N32D). All 6 mutants were expressed in Escherichia coli (BL21) and purified. Xylanase activity showed all mutants have an optimum catalytic temperature (Topt) of 55°C, and with the exception of the S27E mutant, a higher specific activity than the wild-type XynA. The time for loss of 50% activity at 55°C (t50) decreased in the order S22E/N32D>N181R>S22E>Wild-type>S27E=N32D≈N54E. The values of the van't Hoff denaturation enthalpy change (ΔHND), melting temperature (Tm) and heat capacity at constant pressure (ΔCp) between the native and denatured states were estimated from thermal denaturation curves monitored by circular dichroism ellipticity changes. The decreasing order of Gibbs free energy change at 328K (ΔG328) S22E/N32D>N181R>S22E>Wild-type>S27E≈N54E>N32D correlates well with the thermotolerance results, and is dominated by changes in ΔHND which is consistent with increased in hydrogen bonding in the thermostable mutants.


MYBL2, a link between proliferation and differentiation in maturing colon epithelial cells.
Multiple signals, controlling both proliferation and differentiation, must be integrated in the reprogramming of intestinal epithelial cells during maturation along the crypt-luminal axis. The v-myb family member Mybl2, a molecule implicated in the development and maintenance of the stem cell phenotype, has been suggested to play an important role in proliferation and differentiation of several cell types and is a gene we have found is commonly regulated in several systems of colon cell maturation both in vitro and in vivo. Here we show that siRNA silencing of Mybl2 in proliferating Caco-2 cells increases expression of the cell-cycle regulators cdk2, cyclin D2, and c-myc and decreases expression of cdc25B and cyclin B2 with a consequent 10% increase of cells in G2/M and a complementary 10% decrease in G1. Mybl2 occupies sequences upstream of transcriptional start sites of cyclin D2, c-myc, cyclin B2, and cdc25B and regulates reporter activity driven by upstream regions of cdk2, cyclin D2, and c-myc. These data suggest that Mybl2 plays a subtle but key role in linking specific aspects of cell-cycle progression with generation of signals for differentiation and may therefore be fundamental in commitment of intestinal epithelial cells to differentiation pathways during their maturation.


Antinociceptive effect of 1400 W, an inhibitor of inducible nitric oxide synthase, following hind paw incision in rats.
Acute tissue damage is accompanied by synthesis of nitric oxide (NO) in the inflamed tissue as well as in the spinal cord. NO release at the spinal level is likely involved in the neuroplastic changes contributing to pain. Also, previous studies indicate that this could be due to the inducible isoform of the nitric oxide synthase (iNOS) enzyme. Though, the role of NO has been investigated in several animal models of nociception, the precise contribution of NO to nociception arising from hind paw incision is unknown, which is a rodent model of postoperative pain. In the present work, we have estimated the formation of NO in Sprague-Dawley rats, both at the site of incision and the corresponding spinal cord levels by Griess assay. Subsequently, naive rats were implanted with chronic indwelling intrathecal (i.t.) catheters. Fixed quantity (30 μg) of 1400 W, an iNOS inhibitor, was either administered locally into the wound at the time of incision or into the i.t. space, 15 min before hind paw incision. In a different set, i.t. 1400 W was administered, 20 h after incision. Control group received i.t. saline. Nociception was evaluated by guarding score, mechanical allodynia and thermal hyperalgesia. NO level was significantly increased between 4 h - day 1 locally and at 4 h at the spinal level after incision. Local inhibition of iNOS produced transient decrease of guarding (4-12 h) whereas pronounced decrease of guarding and allodynia was evident after spinal inhibition of iNOS. Also, spinal NO level decreased after i.t. drug administration. Post-incision drug treatment resulted in greater antinociceptive effect at day 1 though not on day 2. These results indicate involvement of NO in postincisional nociception in rats.


A comprehensive overview by region of condoms, natural family planning, and spermicide as a contraceptive method among men aged 13-54 years attending contraceptive services in England.
This study aimed to (1) provide a comprehensive overview of contraceptive methods self-reported by men in England, over 5 years, focusing on condoms in comparison to any male method; and (2) explore condom as a contraceptive method by region and ethnicity. Data were from the Sexual and Reproductive Health Services (Contraception) England census data set from 2014/15 to 2018/19. Once missing data were removed, this left a total of 365,292 men. Two binomial logistic regression models were performed. Model 1 examined ethnicity, region, and time on condom as a method of contraception; and Model 2 examined ethnicity, region, and time by any male contraceptive. Descriptive statistics were run for natural family planning and spermicide. Model 1 revealed a significant model, χ2 (15) = 30,976, P < 0.001, and predicted that condoms as a method decreased in London with a greater decrease in Midlands. London saw the lowest rate of decline among the non-White ethnic group, whereas North and South regions increased probability over time. The North started at a higher probability and the South at the lowest. Model 2 also revealed a significant model, χ2 (15) = 32,472, P < 0.001, with a similar pattern to Model 1. Contingency tables showed natural family planning and spermicide were the least reported methods and decreased over time. As any male contraceptive method appears to be decreasing in both models, reproductive health promotion is required. This study has implications for commissioning funds and for identifying regional areas of further investigation.


Role of xanthine dehydrogenase and aging on the innate immune response of Drosophila.
It has been proposed that uric acid is an important scavenger of deleterious oxygen species and peroxynitrite in biological systems. The cellular sources responsible for the generation of damage-causing reactive oxygen species (ROS) are widespread. Xanthine dehydrogenase (XDH) / oxidase (XOD) catalyzes the oxidation of xanthine to uric acid. The rosy (ry) gene encodes XDH/XOD in Drosophila melanogaster. XDH codes for uric acid which is a ROS scavenger. XOD however is an enzyme system implicated in ROS production. In this study, we investigated the roles of XDH in the fly's immune defense response to infection and in the aging process. We first compared ROS generation and nitric oxide (NO) level in the whole body and the gut of XDH mutant with those of wild type. Our results suggested that XDH has a protective effect with respect to both ROS and NO generations, particularly in the gut. We also examined the effect of a XDH deletion mutant on the relative sensitivity of the organism against bacterial infection, on the immune inducibility of antimicrobial peptides and on the effect of aging in the defensive response to infection. Our results strongly suggest that XDH plays an important role in the innate immune response and that the age-associated deterioration of the innate immune response might be, at least in part, associated with the loss of XDH activity in the aging process.


[Autoimmune hepatitis].
Autoimmune hepatitis is a chronic liver disease characterized by a necroinflammatory activity of the portal tract resulting from an immune response against hepatocytes. It is relatively rare and its cause is unknown. There are three types (I, II and III) associated with the presence of some autoantibodies which are not always specific. The diagnosis is based on clinical, biochemical, immunological and histological features. The preferred treatment is a combination regimen of predniso(lo)ne and azathioprine (budezonide and aziathioprine in when cirrhosis is absent). The corticosteroid must be slowly tapered down keeping the immunosuppressive agent as maintenance therapy. Drug withdrawal should only be considered whether serum transaminases and γ-globulins level are normal and after a normal or near normal liver biopsy.


Tumor cells convert immature myeloid dendritic cells into TGF-beta-secreting cells inducing CD4+CD25+ regulatory T cell proliferation.
The mechanisms through which regulatory T cells accumulate in lymphoid organs of tumor-bearing hosts remain elusive. Our experiments indicate that the accumulation of CD4+CD25+ regulatory T cells (T reg cells) expressing FoxP3 and exhibiting immunosuppressive function originates from the proliferation of naturally occurring CD25+ T cells and requires signaling through transforming growth factor (TGF)-beta receptor II. During tumor progression, a subset of dendritic cells (DCs) exhibiting a myeloid immature phenotype is recruited to draining lymph nodes. This DC subset selectively promotes the proliferation of T reg cells in a TGF-beta-dependent manner in mice and rats. Tumor cells are necessary and sufficient to convert DCs into regulatory cells that secrete bioactive TGF-beta and stimulate T reg cell proliferation. In conclusion, tumor expansion can stimulate T reg cells via a specific DC subset.


Effect of Guizhifulingwan (Keishibukuryogan) on climacteric syndrome: study protocol for a randomized controlled pilot trial.
The aim of this study is to explore the efficacy of Guizhifulingwan (GFW) in the treatment of climacteric syndrome in women. This is a single-center, randomized, placebo-controlled, parallel-group design pilot trial. Fifty participants with climacteric syndrome will be randomly allocated to the GFW or placebo group in a 1:1 ratio. The participants will be administered GFW or placebo granules three times a day for 4 weeks and will be followed up for a further 4 weeks. The primary outcome is the mean change in menopause rating scale score at 5 weeks after randomization. Secondary outcomes include the World Health Organization quality of life-BREF scores, degrees of upward movement of qi and lower abdominal resistance and tenderness, blood stasis pattern questionnaire scores, and results of blood tests including assays for lipid profile, high sensitivity C-reactive protein, follicle-stimulating hormone, and estradiol. The feasibility outcomes include recruitment and completion rates and adherence to medication. The results of this study will provide basic data for the design of a large-scale clinical trial for evaluating the efficacy of GFW in the treatment of climacteric syndrome in women. Clinical Research Information Service (CRIS), Republic of Korea, KCT0002040 . Registered on 5 September 2016.


Cardiomyocyte-Restricted Expression of IL11 Causes Cardiac Fibrosis, Inflammation, and Dysfunction.
Cardiac fibrosis is a common pathological process in heart disease, representing a therapeutic target. Transforming growth factor β (TGFβ) is the canonical driver of cardiac fibrosis and was recently shown to be dependent on interleukin 11 (IL11) for its profibrotic effects in fibroblasts. In the opposite direction, recombinant human IL11 has been reported as anti-fibrotic and anti-inflammatory in the mouse heart. In this study, we determined the effects of IL11 expression in cardiomyocytes on cardiac pathobiology and function. We used the Cre-loxP system to generate a tamoxifen-inducible mouse with cardiomyocyte-restricted murine Il11 expression. Using protein assays, bulk RNA-sequencing, and in vivo imaging, we analyzed the effects of IL11 on myocardial fibrosis, inflammation, and cardiac function, challenging previous reports suggesting the cardioprotective potential of IL11. TGFβ stimulation of cardiomyocytes caused Il11 upregulation. Compared to wild-type controls, Il11-expressing hearts demonstrated severe cardiac fibrosis and inflammation that was associated with the upregulation of cytokines, chemokines, complement factors, and increased inflammatory cells. IL11 expression also activated a program of endothelial-to-mesenchymal transition and resulted in left ventricular dysfunction. Our data define species-matched IL11 as strongly profibrotic and proinflammatory when secreted from cardiomyocytes and further establish IL11 as a disease factor.


Fate of synthetic musks in a domestic wastewater treatment plant and in an agricultural field amended with biosolids.
Synthetic musks are widely used as fragrance ingredients in personal care products, and they enter domestic wastewater treatment plants (WWTPs) through discharges into municipal sewage systems. Samples of aqueous sewage and biosolids collected from the Peterborough Wastewater Treatment Plant (WWTP), Ontario, Canada were analyzed for 11 synthetic musk compounds using GC/MS. The results showed that 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethyl-cyclopenta[g]-2-benzopyrane (HHCB, 173.1+/-43.4 ng/L) and 7-acetyl-1,1,3,4,4,6-hexamethyl-tetrahydronaphthalene (AHTN, 41.6+/-15.8 ng/L) were the dominant fragrances in sewage, but other polycyclic musks and nitro musks were present at lower concentrations. The concentrations of HHCB and AHTN in the aqueous phase of the sewage were highly correlated with both BOD5 and TOC. The overall removal efficiency of synthetic musks from the aqueous sewage in the WWTP ranged from 43.3% to 56.9%, but removal occurred mainly by partitioning into the biosolids. Based on a mass balance model, the daily input and output of HHCB and AHTN in the Peterborough WWTP were 47 g and 46 g, respectively. In an agricultural field amended with biosolids from the Peterborough WWTP, HHCB and AHTN were detected in soil immediately after application at mean concentrations of 1.0 and 1.3 mug/kg, respectively, but concentrations declined relatively rapidly over the next 6 weeks, post-application.


Rate and variability of finger tapping as measures of lateralized concurrent task effects.
Using a sample of 48 normal right-handed adults, we assessed the effects of oral reading on concurrent unimanual finger tapping under all combinations of instructional set (speeded vs. consistent tapping), tapping movement (repetitive vs. alternating), task emphasis (reading emphasized vs. tapping emphasized), and tapping hand. Change in tapping rate and variability was measured relative to the corresponding single task control condition. Reading decreased the rate of speeded finger tapping but increased the rate of consistent tapping. In both instances, the right hand was affected more than the left hand. Asymmetries were comparable for repetitive and alternating tapping. When measured in terms of variability, however, effects were largely symmetric. The findings clarify the conditions under which lateralized concurrent task effects are most likely to occur and show that such effects are not statistical artifacts. It appears that subjects attempt to coordinate the timing of concurrent activities and that speech timing is more strongly linked to right-hand control than to left-hand control in right-handers.


Even low light pollution levels affect the spatial distribution and timing of activity of a "light tolerant" bat species.
By disrupting nocturnal landscapes worldwide, light pollution caused by Artificial Light At Night (ALAN) is recognized as a major threat to biodiversity. As even low light intensities might affect some taxa, concerns are arising about biological responses to widespread low light levels. We used data from a French citizen science bat monitoring program (1894 full-nights monitored on 1055 sites) to explore the landscape-scale effects of light on an open-space-foraging bat species, the Serotine bat (Eptesicus serotinus). We assessed this species' abundance and timing of night-time activity (median time of activity) at foraging sites. ALAN, and to a lesser extent moonlight, reduced E. serotinus abundance. ALAN delayed activity, and this delay was amplified during overcast nights. On the contrary, where there was no ALAN, the higher the cloud cover, the earlier the activity occurred. Cloud cover likely darkened the night sky in rural locations, whereas it amplified skyglow in light-polluted places, increasing ALAN effects on bats. Interestingly, moonlight also delayed activity but this effect was weakened where there was ALAN. Our study shows that even fine variations of light levels could affect the spatiotemporal distribution of a common species usually considered to be "light tolerant", with potential cascading effects on individual fitness and population dynamics. It stresses how urgent it is to preserve and restore dark areas to protect biodiversity from light pollution while working on light intensity and directivity where ALAN is needed.


In Vivo Absolute Metabolite Quantification Using a Multiplexed ERETIC-RX Array Coil for Whole-Brain MR Spectroscopic Imaging.
Absolute quantification of metabolites in MR spectroscopic imaging (MRSI) requires a stable reference signal of known concentration. The Electronic REference To access In vivo Concentrations (ERETIC) has shown great promise but has not been applied in patients and 3D MRSI. ERETIC hardware has not been integrated with receive arrays due to technical challenges, such as coil combination and unwanted coupling between multiple ERETIC and receive channels, for which we developed mitigation strategies. To develop absolute quantification for whole-brain MRSI in glioma patients. Prospective. Five healthy volunteers and three patients with isocitrate dehydrogenase mutant glioma (27% female). Calibration and coil loading phantoms. A 3 T; Adiabatic spin-echo spiral 3D MRSI with real-time motion correction, Fluid Attenuated Inversion Recovery (FLAIR), Gradient Recalled Echo (GRE), Multi-echo Magnetization Prepared Rapid Acquisition of Gradient Echo (MEMPRAGE). Absolute quantification was performed for five brain metabolites (total N-acetyl-aspartate [NAA]/creatine/choline, glutamine + glutamate, myo-inositol) and the oncometabolite 2-hydroxyglutarate using a custom-built 4x-ERETIC/8x-receive array coil. Metabolite quantification was performed with both EREIC and internal water reference methods. ERETIC signal was transmitted via optical link and used to correct coil loading. Inductive and radiative coupling between ERETIC and receive channels were measured. ERETIC and internal water methods for metabolite quantification were compared using Bland-Altman (BA) analysis and the nonparametric Mann-Whitney test. P < 0.05 was considered statistically significant. ERETIC could be integrated in receive arrays and inductive coupling dominated (5-886 times) radiative coupling. Phantoms show proportional scaling of the ERETIC signal with coil loading. The BA analysis demonstrated very good agreement (3.3% ± 1.6%) in healthy volunteers, while there was a large difference (36.1% ± 3.8%) in glioma tumors between metabolite concentrations by ERETIC and internal water quantification. Our results indicate that ERETIC integrated with receive arrays and whole-brain MRSI is feasible for brain metabolites quantification. Further validation is required to probe that ERETIC provides more accurate metabolite concentration in glioma patients. 2 TECHNICAL EFFICACY: Stage 1.


Determination of corporate water consumption: Evidence from precipitation risks in China.
We study the causal impact of precipitation risks on corporate water consumption decisions by combining daily precipitation data in mainland China with industrial firm water use data from 1998 to 2013. Using a large sample yielding precise estimates, we find that precipitation shocks significantly impact a firm's water usage, in which the higher the risk of precipitation, the less water is used by firms. Furthermore, we find that this water-saving effect is largely driven by potential extreme drought. We also use city-level data to demonstrate that precipitation is an important driver of corporate water-saving measures. The water-saving effects of precipitation uncertainty and extreme precipitation have particularity in areas that are more sensitive to precipitation and high-water-consumption industrial enterprises. Finally, the results reveal that firms mainly realize the water-saving effect of precipitation risk through technological improvement, reduction of wastewater discharge, and abbreviation of investment and production scale.


Altered lignocellulose chemical structure and molecular assembly in CINNAMYL ALCOHOL DEHYDROGENASE-deficient rice.
Lignin is a complex phenylpropanoid polymer deposited in plant cell walls. Lignin has long been recognized as an important limiting factor for the polysaccharide-oriented biomass utilizations. To mitigate lignin-associated biomass recalcitrance, numerous mutants and transgenic plants that produce lignocellulose with reduced lignin contents and/or lignins with altered chemical structures have been produced and characterised. However, it is not fully understood how altered lignin chemistry affects the supramolecular structure of lignocellulose, and consequently, its utilization properties. Herein, we conducted comprehensive chemical and supramolecular structural analyses of lignocellulose produced by a rice cad2 mutant deficient in CINNAMYL ALCOHOL DEHYDROGENASE (CAD), which encodes a key enzyme in lignin biosynthesis. By using a solution-state two-dimensional NMR approach and complementary chemical methods, we elucidated the structural details of the altered lignins enriched with unusual hydroxycinnamaldehyde-derived substructures produced by the cad2 mutant. In parallel, polysaccharide assembly and the molecular mobility of lignocellulose were investigated by solid-state 13C MAS NMR, nuclear magnetic relaxation, X-ray diffraction, and Simon's staining analyses. Possible links between CAD-associated lignin modifications (in terms of total content and chemical structures) and changes to the lignocellulose supramolecular structure are discussed in the context of the improved biomass saccharification efficiency of the cad2 rice mutant.


Isolation of human antibodies against hepatitis E virus from phage display library by immobilized metal affinity chromatography.
To isolate human antibodies against hepatitis E virus from phage display library by a new method of panning phage antibody library based on immobilized metal affinity chromatography (IMAC). Phage antibody library was allowed to mix with hex-His tagged expressed HEV specific antigen, NE2, in solution for adequate binding before affinity resin for hex-His was added. The non-specific phage antibodies were removed by extensive washing and the specific bound phage antibodies could then be eluted to infect TG1 or repeat the binding process for subsequent rounds of purification. The specificity of the selected human antibodies were tested by antigen competitive ELISA, human sera blocking ELISA, scFv expression, and sequence analysis. His-NE2 specific recombinant phages were successfully enriched after panning procedure. Two individual phage clones, 126 and 138, showed 50% inhibition in NE2 antigen competition ELISA and obvious blocking effect by HEV positive serum in blocking ELISA. Soluble scFv of 126, 138 bound to NE2 specifically. Two specific human phage antibodies against hepatitis E virus (HEV) from phage display library were isolated by immobilized metal affinity chromatography. The immobilized metal affinity chromatography applied to phage antibody selection was a helpful supplement to the selection in solution.


Physical schemata underlying biological pattern formation-examples, issues and strategies.
Biological systems excel at building spatial structures on scales ranging from nanometers to kilometers and exhibit temporal patterning from milliseconds to years. One approach that nature has taken to accomplish this relies on the harnessing of pattern-forming processes of non-equilibrium physics and chemistry. For these systems, the study of biological pattern formation starts with placing a biological phenomenon of interest within the context of the proper pattern-formation schema and then focusing on the ways in which control is exerted to adapt the pattern to the needs of the organism. This approach is illustrated by several examples, notably bacterial colonies (diffusive-growth schema) and intracellular calcium waves (excitable-media schema).


One- and two-hybrid analysis of the interactions between components of the Trypanosoma cruzi spliced leader RNA gene promoter binding complex.
The spliced leader (SL) RNA gene promoter is the only RNA polymerase II-dependent promoter characterized to date in trypanosomatids. Transcription of this small nuclear RNA is critical for trypanosomatid cell life because it is needed for polycistronic primary transcripts processing into individual translatable mRNAs. In recent years, a set of divergent fundamental transcription factors required for SL RNA gene transcription have been identified in different trypanosomatids. By means of a yeast two-hybrid system, we analyzed the protein-protein interactions between components of the SL RNA gene promoter binding complex. We also studied the interactions of already described motifs of TATA-binding protein (TBP) and transcription factor II B (TFIIB) orthologs separately. This was followed by investigations of DNA-protein interactions within the SL RNA gene promoter binding complex using one-hybrid analysis. Our results suggest that the complex has two "cores" which contact the promoter DNA, trypanosomal small nuclear RNA activating protein complex (tSNAPc), which has strong interactions between its subunits and a more labile TBP-TFIIA sub-complex.


Nerve growth factor, brain-derived neurotrophic factor and their high-affinity receptors are overexpressed in extramammary Paget's disease.
Neurotrophin (NT) systems appear to play important roles in the pathogenesis of several tumors, but their expression in extramammary Paget's disease (EPD) has not been investigated. Thirty-four paraffin-embedded EPD specimens (32 primary EPD and 2 metastatic to lymph nodes) were subject to immunohistochemical staining for nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), NT3, NT4, their high-affinity receptors (TrkA, TrkB and TrkC) and the common low-affinity receptor, p75 NT receptor (p75). All 34 EPD specimens, including 2 metastatic to lymph nodes, showed cytoplasmic overexpression of NGF, BDNF, TrkA and TrkB. The expression (% positive cells) of NGF, BDNF, NT3, NT4, TrkA and TrkB (81.6 ± 14.9, 86.0 ± 10.4, 89.6 ± 14.9, 87.8 ± 17.9, 83 ± 14.4 and 86.2 ± 11.7%) in EPD was significantly higher than in normal skin (21.6 ± 6.5, 27.6 ± 4.5, 19.7 ± 10.1, 8.2 ± 10.0, 25.0 ± 5.3 and 25.4 ± 6.4%), and the expression of these factors in invasive EPD was significantly higher than in noninvasive EPD. Interestingly, Paget cells were negative for p75 and TrkC in all the 34 EPD specimens. These results suggest that overexpression of NGF, BDNF and their high-affinity receptors (TrkA and TrkB) might play a role in the pathogenesis of EPD.


PICOT is a critical regulator of cardiac hypertrophy and cardiomyocyte contractility.
PICOT (PKC-interacting cousin of thioredoxin) was previously shown to inhibit the development of cardiac hypertrophy, concomitant with an increase in cardiomyocyte contractility. To explore the physiological function of PICOT in the hearts, we generated a PICOT-deficient mouse line by using a gene trap approach. PICOT(-/-) mice were embryonic lethal indicating that PICOT plays an essential role during embryogenesis, whereas PICOT(+/-) mice were viable with no apparent morphological defects. The PICOT protein levels were reduced by about 50% in the hearts of PICOT(+/-) mice. Significantly exacerbated cardiac hypertrophy was induced by pressure overload in PICOT(+/-) mice relative to that seen in wild type littermates. In line with this observation, calcineurin-NFAT signaling was greatly enhanced by pressure overload in the hearts of PICOT(+/-) mice. Cardiomyocytes from PICOT(+/-) mice exhibited significantly reduced contractility, which may be due in part to hypophosphorylation of phospholamban and reduced SERCA activity. These data indicate that the precise PICOT protein level significantly affects the process of cardiac hypertrophy and cardiomyocyte contractility. We suggest that PICOT plays as a critical negative regulator of cardiac hypertrophy and a positive inotropic regulator.


Making sense of the cancer journey: Pediatric cancer survivors' and their parents' autobiographical memories.
Youth diagnosed with acute lymphoblastic leukemia (ALL) and their caregiver's experience a myriad of challenges in all domains of health that extend beyond treatment. Yet, little is known about how the cancer experience, and recollections associated with the experience, impact survivorship. We explored pediatric ALL survivors' and their caregivers' autobiographical memories of the cancer experience from diagnosis onwards. Survivors of ALL, and one of their caregivers, were recruited through a local clinic. Survivors and their caregivers completed a demographic survey and semi-structured, private, one-on-one interviews. Demographic information were analyzed using descriptive statistics. Interviews were transcribed verbatim and analyzed using reflexive thematic analysis at the level of the individual and dyad. Insights from survivors (N = 19; Mage = 15.3 years) and their caregivers (n = 19; Mage = 45.4 years) were captured. Analyses generated two themes contingent on role (i.e., survivor or caregiver): (1) It is hard to recall my cancer experience and (2) We did as much as we could to manage our child's cancer experience and two unified themes (present in both survivors and their caregivers): (3) It took a village to get through the cancer experience and (4) The cancer diagnosis and experience has had a lasting impact. Findings highlight the varied and long-lasting ways cancer impacts survivors of pediatric ALL and their caregivers. Survivors had difficultly remembering their experience or felt that information was withheld and were acutely aware of their caregiver's distress. Caregivers were cautious and intentionally limited the information they shared. Survivors desired to be included within, or told about, decisions related to their healthcare and were acutely aware of their caregiver's distress. Efforts should be made to communicate with survivors (from diagnosis onward) openly and to consider strategies to minimize the short- and long-term impacts of pediatric ALL among survivors and their caregivers.


Temporal arteritis and sensorineural hearing loss.
The association of temporal arteritis and sensorineural hearing loss is a rare occurrence. We present four cases with both these disorders. A 10-year retrospective review of all cases seen at the Geisinger Medical Center showed 271 cases of temporal arteritis and four cases with concomitant sensorineural hearing loss. The four cases were identified, obtained, and extensively reviewed. Patients ranged in age from 59 to 76 years and presented with sensorineural hearing loss and signs, symptoms, and biopsy evidence of temporal arteritis. The response to therapy and clinical course of each case are discussed. In three patients, the hearing loss preceded the diagnosis of giant cell arteritis by 2 days to 2 months. In one case, the hearing loss was noted concurrently with systemic features of giant cell arteritis. All cases were treated with corticosteroids and had full or partial return of hearing. Sensorineural hearing loss can be a preceding or concurrent symptom of temporal arteritis. Recognition and treatment may lead to partial or full recovery. It is not certain whether the time from onset of hearing loss to diagnosis to institution of therapy influences recovery.


Preferential Iron Trafficking Characterizes Glioblastoma Stem-like Cells.
Glioblastomas display hierarchies with self-renewing cancer stem-like cells (CSCs). RNA sequencing and enhancer mapping revealed regulatory programs unique to CSCs causing upregulation of the iron transporter transferrin, the top differentially expressed gene compared with tissue-specific progenitors. Direct interrogation of iron uptake demonstrated that CSCs potently extract iron from the microenvironment more effectively than other tumor cells. Systematic interrogation of iron flux determined that CSCs preferentially require transferrin receptor and ferritin, two core iron regulators, to propagate and form tumors in vivo. Depleting ferritin disrupted CSC mitotic progression, through the STAT3-FoxM1 regulatory axis, revealing an iron-regulated CSC pathway. Iron is a unique, primordial metal fundamental for earliest life forms, on which CSCs have an epigenetically programmed, targetable dependence.


Implantable pneumatically actuated microsystem for renal pressure-mediated transfection in mice.
In vivo transfection is an important technique used in biological research and drug therapy development. Previously, we developed a renal pressure-mediated transfection method performed by pressing a kidney after an intravenous injection of naked nucleic acids. Although this is a useful method because of its safety and wide range of applications, an innovative approach for performing this method without repeatedly cutting open the abdomen is required. In this study, we developed an implantable microsystem fabricated by Micro-Electro-Mechanical Systems (MEMS) technologies for renal pressure-mediated transfection. The system consists of a polydimethylsiloxane pneumatic balloon actuator (PBA) used as an actuator to press the target kidney. The PBA of the implanted microsystem can be actuated without opening the abdomen by applying air pressure from outside the body to the pressure-supplying port via a needle. We successfully performed renal pressure-mediated transfection using the newly developed system when the implanted system was activated at 60kPa for 10s. This is the first report of an implantable MEMS-based microsystem that demonstrates in vivo transfection to a kidney using naked plasmid DNA.


A New Possibility for Fermentation Monitoring by Electrical Driven Sensing of Ultraviolet Light and Glucose.
Industrial fermentation generates products through microbial growth associated with the consumption of substrates. The efficiency of industrial production of high commercial value microbial products such as ethanol from glucose (GLU) is dependent on bacterial contamination. Controlling the sugar conversion into products as well as the sterility of the fermentation process are objectives to be considered here by studying GLU and ultraviolet light (UV) sensors. In this work, we present two different approaches of SnO2 nanowires grown by the Vapor-Liquid-Solid (VLS) method. In the GLU sensor, we use SnO2 nanowires as active electrodes, while for the UV sensor, a nanowire film was built for detection. The results showed a wide range of GLU sensing and as well as a significant influence of UV in the electrical signal. The effect of a wide range of GLU concentrations on the responsiveness of the sensor through current-voltage based on SnO2 nanowire films under different concentration conditions ranging was verified from 1 to 1000 mmol. UV sensors show a typical amperometric response of SnO2 nanowires under the excitation of UV and GLU in ten cycles of 300 s with 1.0 V observing a stable and reliable amperometric response. GLU and UV sensors proved to have a promising potential for detection and to control the conversion of a substrate into a product by GLU control and decontamination by UV control in industrial fermentation systems.


Genetic characterization of clinically relevant class 1 integrons carried by multidrug resistant bacteria (MDRB) isolated from the gut microbiota of highly antibiotic treated Salmo salar.
The main objective of this study was the genetic characterization of clinically relevant class 1 integrons carried by multidrug resistant bacteria isolated from the intestinal microbiota of aquaculture salmon treated with high concentrations of antibiotics. In 82 multidrug resistant bacterial isolates, the prevalence of both the conserved elements of the integrons, qacEΔ1 and sul1 genes, and the variable region (VR) was determined. Further, whole genome sequencing and complete genetic analysis was performed in VR-positive isolates. Despite the fact that 100% of the bacterial isolates presented the intI1 gene, only 12.3% carried the qacEΔ1 and sul1 genes and only two (2.4%) presented a VR with gene cassettes. In the Pseudomonas baetica 25P2F9 isolate, a VR carrying aac(6')31, qacH, and blaOXA-2 gene cassettes was described, whereas the VR of Aeromonas salmonicida 30PB8 isolate showed a dfrA14 gene cassette. The array of gene cassettes found in the Pseudomonas isolate appears with high frequency in clinically relevant pathogens such as Pseudomonas aeruginosa or Escherichia coli. Additionally, it was possible to determine that these integrons are contained in plasmids and coul be easily transferred. Resistome analysis demonstrated that both isolates carried a great diversity of antibiotic resistance genes, including many β-lactamases. Even in the Aeromonas isolate a new oxacillin-hydrolyzing beta-lactamase gene was described (blaOXA-956). The presence of multidrug resistant bacteria and clinically relevant genetic elements in the salmon intestinal microbiota make the aquaculture a hotspot in the phenomenon of antibiotic resistance; therefore, the control of antibiotics used in this activity is a key point to avoid its escalation.


The Quix test.
Professor Doctor F.H. Quix, of Utrecht, was a keen student of macular function, who published extensively at the beginning of this century. He described many useful tests for otolithic function, and one in particular has continued to be fairly widely used. The so-called "Quix Test" is performed with the patient standing, feet slightly apart, arms outstretched, index fingers extended, and the examiner assumes a similar mirror-image posture, such that the fingertips almost touch. The patient is then requested to close his eyes, and the index fingers are observed for drift. The lateralizing value of this sign of vestibular disease is discussed.


Synthesis of [11C]palmitic acid for PET imaging using a single molecular sieve 13X cartridge for reagent trapping, radiolabeling and selective purification.
Radiolabeled fatty acids are valuable metabolic tracers for PET imaging. Carbon-11 is widely used in clinical PET studies due to the prevalence of facile techniques enabling the incorporation of [(11)C]CO2 and [(11)C]CH3 into molecules and a short half-life (20.4 min) that translates into low patient dose. However, the short half-life considerably limits the time for radiosynthesis. Furthermore, the majority of the syntheses of [(11)C]palmitic acid in common use employ high starting [(11)C]CO2 activities and/or expensive equipment. [(11)C]CO2 was trapped with greater than 99.99% efficiency by a three stage cartridge packed with molecular sieve 13X, 100-120 mesh. The labeling of n-pentadecylmagnesium bromide took place in 5 min in the cartridge, and the [(11)C]palmitic acid product was selectively eluted in ethanol following alkaline and acidic washes of the column. The system reliably produced more than 925 MBq (25 mCi) of [(11)C]palmitic acid suitable for human use from 7.4 GBq (200 mCi) of [(11)C]CO2 in 8 min from end-of-bombardment. We have exploited the properties of the inexpensive molecular sieve 13X to develop a miniature, disposable and leak tight "gas capture" system for the rapid labeling and purification of [(11)C]fatty acids in good yield and >99% radiochemical purity. The rapidity of the synthesis and purification allows small [(11)C]CO2 starting activities to be used, and with no requirement for expensive synthesis equipment or facilities, the system can be implemented in any radiopharmaceutical center.


Stranger danger? The intersectional impacts of shared housing on young people's health & wellbeing.
Recent housing welfare reform in Britain has left many younger welfare claimants with no choice but to move into a shared rental property with strangers. In this paper we take an intersectional approach to analyzing the impact of housing welfare reform, by examining how certain protected equalities groups may be particularly at risk from the potential harms of shared living with strangers. Drawing upon in-depth biographical interview data, we outline how young people often spoke of their share houses as places that were detrimental to their health and wellbeing. Our analysis focuses on two key themes: physical safety and violence, followed by mental health and isolation. Ultimately the paper examines whether housing welfare reform in Britain has resulted in placing already vulnerable people into potentially dangerous and unhealthy housing situations.


The multisubunit structure of synaptophysin. Relationship between disulfide bonding and homo-oligomerization.
Synaptophysin, a major membrane protein of synaptic vesicles, contains four transmembrane regions and two intravesicular loops. Synaptophysin monomers associate into homopolymers that have the potential to form channels in the synaptic vesicle membrane. Here we show that in native synaptophysin, homopolymers are linked by noncovalent forces. The molecule contains unstable intramolecular disulfide bonds that undergo disulfide exchange during solubilization, thereby covalently cross-linking neighboring synaptophysin molecules. The locations of the intramolecular disulfide bonds in synaptophysin were determined, revealing that each of the two intravesicular loops of synaptophysin is circularized by a single disulfide bond. Cross-linking of synaptophysin by disulfide bonds can be triggered in synaptic vesicles and in intact cells by a cycle of reduction and oxidation, suggesting that native synaptophysin is a homomultimer in situ. In addition, chemical cross-linking of native synaptophysin demonstrates that a low molecular weight protein is specifically associated with synaptophysin complexes and is lost upon reduction of the intramolecular disulfide bonds. These data suggest that native synaptophysin forms a noncovalent homomultimeric complex whose structure and interaction with other proteins are dependent on the integrity of its intramolecular disulfide bonds and phospholipid environment.


Prevention of passively transferred experimental autoimmune myasthenia gravis by an in vitro selected RNA aptamer.
Myasthenia gravis (MG) and its animal model, experimental autoimmune MG (EAMG), are mainly caused by autoantibodies directed against acetylcholine receptors (AChR) located in the postsynaptic muscle membrane. Previously, we isolated an RNA aptamer with 2'-fluoropyrimidines using in vitro selection techniques that acted as an effective decoy against both a rat monoclonal antibody called mAb198, which recognizes the main immunogenic region on the AChR, and a significant fraction of patient autoantibodies with MG. To investigate the therapeutic potential of the RNA, we tested the ability of the RNA aptamer to protect the receptors in vivo from mAb198. Clinical symptoms of EAMG in rats engendered by passive transfer of mAb198 were efficiently inhibited by a truncated RNA aptamer that was modified with polyethylene glycol, but not by control scrambled RNA. Moreover, the loss of AChR in the animals induced by the antibody was also significantly blocked with the modified RNA aptamer. These results suggested that RNA aptamers could be applied for antigen-specific treatment for autoimmune diseases including MG.


Self-injury in people with intellectual disability and epilepsy: a matched controlled study.
We aimed to identify the presence of self-injurious behavior in a sample of 158 people with intellectual disability and epilepsy as compared with a control sample consisting of 195 people with intellectual disability without epilepsy. The Italian Scale for the Assessment of self-injurious behaviors was used to describe self-injurious behavior in both groups. The groups were matched for ID degree: mild/moderate (20 and 20 respectively), severe/profound (45 in both samples) and unknown (4 in both samples). Seventy-four percent of the first sample were diagnosed with symptomatic partial epilepsy. The prevalence of self-injurious behaviors was 44% in the group with intellectual disability and epilepsy and 46.5% in the group with intellectual disability without epilepsy (difference not significant). The areas most affected by self-injurious behaviors in both samples were the hands, the mouth and the head. The most frequent types of self-injurious behaviors were self-biting, self-hitting with hands and with objects. Self-injurious behavior is frequently observed in individuals with epilepsy and intellectual disability. Our study does not suggest that the presence of epilepsy is a risk factor for self-injurious behavior in this patient group.


A 73-Year-Old Woman With Progressive Shortness of Breath and Right-Sided Hemithorax Opacity.
A 73-year-old frail woman presented with 3 months of progressively worsening exertional dyspnea, mild cough with white mucus, voice changes, and few episodes of dysphagia. She denied weight loss, night sweats, chest pain, or hemoptysis. Medical history was significant for hypertension, remote 30 years of tobacco use, and regular alcohol use. She had neither asbestos nor occupational exposure. She had no family history of malignancy.


Prediction of Human Pharmacokinetics and Clinical Effective Dose of SI-B001, an EGFR/HER3 Bi-specific Monoclonal Antibody.
SI-B001 is a new EGFR/HER3 bi-specific antibody showing encouraging anti-tumor efficacy in the preclinical studies and was ready for further clinical research. To help with the dose design, human pharmacokinetics (PK) and clinical effective doses of SI-B001 were predicted by PK and PK/PD modeling and simulation. A Michaels-Menten (M-M) PK model was first used to describe the PK of SI-B001 in cynomolgus monkeys, whose parameters were allometrically scaled to humans for the simulation of human PK profiles. Besides, the anti-tumor efficacy of SI-B001 on different xenografts in tumor-bearing mice was quantitatively described by PK/PD models. The clinical effective doses were predicted by comparing the effective exposure (AUCs) in mice with simulated human AUCs. The clinical effective doses of SI-B001 were predicted to be over 16 mg/kg, 5-7 mg/kg or 5-6 mg/kg per week for colon cancer, head and neck cancer or esophageal cancer, respectively, which may help with the optimization of dose escalation schemes and the selection of indications for SI-B001.


The effects of economic development and built environment on diabetes in CHINA.
With rapid economy growth, the prevalence of obesity, and related chronic diseases, has increased greatly. Although this has been widely recognized, little attention has been paid to the influence of built environment and economic growth, particularly for developing countries. The main purpose of this study is to investigate the potential relationship between the prevalence of diabetes and the built environment while considering the effects of socioeconomic change in China. Three nationally representative samples are constructed and employed mainly based on various sources of data, such as the China National Nutrition and Health Survey, World Health Organization, and China Health and Retirement Longitudinal Survey in 2013. The explanatory variables representing the built environment and influential factors include the health outcomes, economic indicators, local health facilities, regional dummies, and demographic features. OLS, robust regressions, and a set of binary choice models are used to estimate the possible relationship. It is suggested that the prevalence of diabetes is associated with both the broader built environment and individual economic factors in China. China's sharp economic growth in the recent decades has greatly increased the prevalence of obesity and diabetes, when also considering other influential factors. Although the results can not specify causal mechanism, some useful results can be clearly discovered and subsequently a few important policy implications can be provided for the sustainable and healthy development of China's urban planning or built environment.


Single-cell chromatin state analysis with Signac.
The recent development of experimental methods for measuring chromatin state at single-cell resolution has created a need for computational tools capable of analyzing these datasets. Here we developed Signac, a comprehensive toolkit for the analysis of single-cell chromatin data. Signac enables an end-to-end analysis of single-cell chromatin data, including peak calling, quantification, quality control, dimension reduction, clustering, integration with single-cell gene expression datasets, DNA motif analysis and interactive visualization. Through its seamless compatibility with the Seurat package, Signac facilitates the analysis of diverse multimodal single-cell chromatin data, including datasets that co-assay DNA accessibility with gene expression, protein abundance and mitochondrial genotype. We demonstrate scaling of the Signac framework to analyze datasets containing over 700,000 cells.


Prediction of peak expiratory flow rates in stunted children.
To assess the effect of stunting on peak expiratory flow rates (PEFR) in Malawian children. Cross sectional study. Two public primary schools randomly selected in Blantyre, the largest city in Malawi. 266 boys and 273 girls aged six to 14 years. PEFR, height, weight and age of children were determined using standard techniques. Nutritional status of children was assessed using WHO/NCHS height for age, weight for age and weight for height reference standards. The data of PEFR were analysed by regression on age and stature. One hundred children (18.6%) were classified as stunted. None of them was under weight or wasted. The equations for prediction of PEFR were calculated separately for stunted and non-stunted children. Stature was a significant predictor of PEFR values in both groups of children. The differences between stunted and non-stunted children of both sexes in slopes and intercepts of the regression lines of PEFR on stature were non-significant. Stunted children of both sexes had significantly lower PEFR than their counterparts with normal height for age index. Stunting in Malawian children aged six to 14 years is associated with decreased rate of development of PEFR in proportion to linear growth retardation. Prediction equations calculated for children with normal height for age index can be used for assessment of PEFR in stunted children.


CONSERTING: integrating copy-number analysis with structural-variation detection.
We developed Copy Number Segmentation by Regression Tree in Next Generation Sequencing (CONSERTING), an algorithm for detecting somatic copy-number alteration (CNA) using whole-genome sequencing (WGS) data. CONSERTING performs iterative analysis of segmentation on the basis of changes in read depth and the detection of localized structural variations, with high accuracy and sensitivity. Analysis of 43 cancer genomes from both pediatric and adult patients revealed novel oncogenic CNAs, complex rearrangements and subclonal CNAs missed by alternative approaches.


Post-integration behavior of a Mos1 mariner gene vector in Aedes aegypti.
The post-integration behavior of insect gene vectors will determine the types of applications for which they can be used. Transposon mutagenesis, enhancer trapping, and the use of transposable elements as genetic drive systems in insects requires transposable elements with high rates of remobilization in the presence of transposase. We investigated the post-integration behavior of the Mos1 mariner element in transgenic Aedes aegypti by examining both germ-line and somatic transpositions of a non-autonomous element in the presence of Mos1 transposase. Somatic transpositions were occasionally detected while germ-line transposition was only rarely observed. Only a single germ-line transposition event was recovered after screening 14,000 progeny. The observed patterns of transposition suggest that Mos1 movement takes place between the S phase and anaphase. The data reported here indicate that Mos1 will be a useful vector in Ae. aegypti for applications requiring a very high degree of vector stability but will have limited use in the construction of genetic drive, enhancer trap, or transposon tagging systems in this species.


A convenient colorimetric assay for the quantification of porcine epidemic diarrhea virus and neutralizing antibodies.
Neonatal enteritis caused by the porcine epidemic diarrhea virus (PEDV) is an important cause of high mortality and economic losses to the swine industry. Virus neutralization (V/N) assays are commonly requested in diagnostic laboratories for the assessment of protective antibodies. However, the visual assessment of viral cytopathic effects by operators to determine antibody titers or for viral quantification is a tedious, subjective and time-consuming process, especially when high volume testing is involved. To improve the ease of testing, a colorimetric virus neutralization and TCID50 assays were developed and validated in this study using (3-(4,5-dimethylthiazol-2-yl) Tr-2,5-diphenyltetrazolium- bromide) (MTT), a colorimetric agent which measures cell viability. The respective conventional assays were used as the gold standards. An OD cut off value of ≤0.53, selected by receiver operating characteristics analysis, could distinguish between wells with and without CPE accurately. Performance and reproducibility parameters of the colorimetric assays were comparable to the conventional assays. The described methods can reduce testing time in diagnostic laboratories, while significantly improving current protocols.


Outcomes of peer mentorship for people living with spinal cord injury: perspectives from members of Canadian community-based SCI organizations.
A generic qualitative design. To obtain a deeper understanding of the outcomes of spinal cord injury (SCI) peer mentorship programs delivered by community-based organizations. Peer mentorship programs of community-based SCI organizations METHODS: We interviewed 36 individuals who shared their experiences of SCI peer mentorship from the perspective of a peer mentee, peer mentor, or family member of a peer mentee/mentor, or staff of SCI community-based organizations. Interview data were analyzed using an inductive thematic analysis approach. Four overarching themes with sub-themes were identified. (1) Positive outcomes for mentees such as understanding, emotional outlet/psychological support, inspiration/hope, and belonging. (2) Positive outcomes for mentors such as gaining gratitude, confidence, pride, and personal growth. (3) Reciprocity in positive/negative outcomes for mentors and mentees, such as shared learning and a lack of connection. (4) Negative outcomes for mentors such as impact of negativity, emotional toll, and time/energy demands. Peer mentorship programs delivered by community-based SCI organizations are important, impactful resources for individuals with SCI who engage in these programs. These results provide insights into the variety of positive and negative outcomes linked with these programs.


The precarious state of the liver after a Fontan operation: summary of a multidisciplinary symposium.
As the cohort of survivors with the single-ventricle type of congenital heart disease grows, it becomes increasingly evident that the state of chronically elevated venous pressure and decreased cardiac output inherent in the Fontan circulation provides the substrate for a progressive decline in functional status. One organ at great risk is the liver. Wedged between two capillary beds, with the pulmonary venous bed downstream, which typically has no pulsatile energy added in the absence of a functional right ventricle, and the splanchnic bed upstream, which may have compromised inflow due to inherent cardiac output restriction characteristic of the Fontan circulation, the liver exists in a precarious state. This review summarizes a consensus view achieved at a multidisciplinary symposium held at The Children's Hospital of Philadelphia in June 2011. The discussion includes current knowledge concerning the hemodynamic foundations of liver problems, the diagnostic tools available, the unique histopathology of the liver after the Fontan operation, and proposed mechanisms for hepatic fibrosis at the cellular level. At the completion of the symposium, a consensus recommendation was made by the authors' group to pursue a new prospective protocol for clinical evaluation of the liver for all patients in our practice 10 years after the Fontan operation.


[Simultaneous determination of kynurenine and tryptophan in serum by high performance liquid chromatography].
A method was established for the simultaneous determination of kynurenine (Kyn) and tryptophan (Trp) in serum by high performance liquid chromatography-ultraviolet detection (HPLC-UV). It employed a Symmetry Shield RP-C18 column (150 mm x 3.9 mm i.d., 5 microm) and a mobile phase of 15 mmol/L sodium acetate-acetic acid solution containing 2.7% (v/v) acetonitrile (pH 3.6) at a flow rate of 1.0 mL/min. The ultraviolet detector was operated at 225 nm. Serum samples were first precipitated with a 5.0% perchloric acid solution, then centrifuged to remove protein residue and finally analyzed by HPLC. The retention time of Kyn was 3.5 min, the linear range of the method was from 0.098 to 49 micromol/L, and the detection limit was 0.02 micromol/L. The recoveries of Kyn were from 90.82% to 93.45%, the intraday and interday variations were 2.37% and 3.66%, respectively. The retention time of Trp was 8.1 min, the linear range of the method was from 4.9 to 490 micromol/L, and the detection limit was 0.20 micromol/L. The recoveries of Trp were from 95.51% to 98.67%, the intraday and interday variations were 1.50% and 2.65%, respectively. The method is simple, fast, accurate, and suitable for routine analysis.


Determination of the effective dose of dexmedetomidine to achieve loss of consciousness during anesthesia induction.
Dexmedetomidine (DEX) is a sedative with greater preservation of cognitive function, reduced respiratory depression, and improved patient arousability. This study was designed to investigate the performance of DEX during anesthesia induction and to establish an effective DEX induction strategy, which could be valuable for multiple clinical conditions. Patients undergoing abdominal surgery were involved in this dose-finding trial. Dixon's up-and-down sequential method was employed to determine the effective dose of DEX to achieve the state of "loss of consciousness", and an effective induction strategy was established with continuous infusion of DEX and remifentanil. The effects of DEX on hemodynamics, respiratory state, EEG, and anesthetic depth were monitored and analyzed. Through the strategy mentioned, the depth of surgical anesthesia was successfully achieved by DEX-led anesthesia induction. The ED50 and ED95 of the initial infusion rate of DEX were 0.115 and 0.200 μg/kg/min, respectively, and the mean induction time was 18.3 min. The ED50 and ED95 of DEX to achieve the state of "loss of consciousness" were 2.899 (95% CI: 2.703-3.115) and 5.001 (95% CI: 4.544-5.700) μg/kg, respectively. The mean PSI on the loss of consciousness was 42.8 among the patients. During anesthesia induction, the hemodynamics including BP and HR were stable, and the EEG monitor showed decreased α and β powers and increased θ and δ in the frontal and pre-frontal cortices of the brain. This study indicated that continuous infusion of combined DEX and remifentanil could be an effective strategy for anesthesia induction. The EEG during the induction was similar to the physiological sleep process.


The Arabidopsis WRINKLED1 transcription factor affects auxin homeostasis in roots.
WRINKLED1 (WRI1) is a key transcriptional regulator of fatty acid biosynthesis genes in diverse oil-containing tissues. Loss of function of Arabidopsis WRI1 leads to a reduction in the expression of genes for fatty acid biosynthesis and glycolysis, and concomitant strong reduction of seed oil content. The wri1-1 loss-of-function mutant shows reduced primary root growth and decreased acidification of the growth medium. The content of a conjugated form of the plant growth hormone auxin, indole-3-acetic acid (IAA)-Asp, was higher in wri1-1 plants compared with the wild-type. GH3.3, a gene encoding an enzyme involved in auxin degradation, displayed higher expression in the wri1-1 mutant. EMSAs demonstrated that AtWRI1 bound to the promoter of GH3.3. Specific AtWRI1-binding motifs were identified in the promoter of GH3.3. In addition, wri1-1 displayed decreased auxin transport. Expression of some PIN genes, which encode IAA carrier proteins, was reduced in wri1-1 plants as well. Correspondingly, AtWRI1 bound to the promoter regions of some PIN genes. It is well known that auxin exerts its maximum effects at a specific, optimal concentration in roots requiring a finely balanced auxin homeostasis. This process appears to be disrupted when the expression of WRI1 and in turn a subset of its target genes are misregulated, highlighting a role for WRI1 in root auxin homeostasis.


[Corporative culture of stomatological institution appraisal by the questionnaire method].
Multiple processes in economics reflect in management and corporative culture of any institution. Long-term motivational influence plays main role in the motivation mechanism; in turn motives form stable and long-term acting system integrated into corporative culture of any stomatological institution. Integration of the interests of the institution and separate members of the staff becomes the basic condition of the interested attitude to work.


Characterization of a new 23 kDalton enkephalin-containing protein in the bovine adrenal medulla.
Immunoblots combined with specific radioimmunoassays (RIAs) have been used to visualize simultaneously all the enkephalin-containing peptides (ECPs) present in a crude extract of bovine adrenal medulla. They have allowed the characterization of a new high molecular weight ECP which has a molecular weight of 23.3 kDalton, contains the amino-terminal part of proenkephalin and ends with the sequence of Leu-enkephalin at its carboxy-terminus.


Reversal of acute monoparesis following thoracoabdominal aortic aneurysm repair.
A 67-year-old man underwent surgical repair for a Crawford extent V thoracoabdominal aortic aneurysm under cerebrospinal fluid drainage and motor evoked potential monitor on distal aortic perfusion. Postoperatively, weakness of right-sided leg graded 2/5 and bladder disorder were recognized. Magnetic resonance imaging revealed hyperintensity between Th11 and L1 on T2-weighted image. Intravenous glycerin and edaravone for spinal cord ischemia had been administered. The strength of right leg resolved completely with disappearance of hyperintensity on magnetic resonance image. Finally, he could walk on foot with bladder disorder.


Expression of T9W in Pichia pastoris and the protective roles of T9W in ICR Mice.
The purpose of this paper is to express the novel α-helical peptide T9W more efficiently using the Pichia pastoris expression system and to examine the role of T9W in ICR mice. The novel antimicrobial peptide T9W was expressed in P. pastoris X-33 by using the vector pPICZαA. Approximately 13 mg/L T9W was secreted from the culture and purified. The expressed peptide has similar activity to the synthetic peptide. ICR female mice challenged with P. aeruginosa 27853 at the LD100 were treated with T9W and CPFX. The results showed that the secretion of inflammatory cytokines and lung damage was significantly reduced by the treatment group, and the protective response was equivalent between T9W and ciprofloxacin-treated mice. T9W was expressed in P. pastoris X-33 via the methanol-inducible vector pPICZαA and exhibited the same biological activity as synthetic T9W. T9W can alleviate damage to mice caused by P. aeruginosa.


Vibration and impulsivity analysis of hand held olive beaters.
To provide more effective evaluations of hand arm vibration syndromes caused by hand held olive beaters, this study focused on two aspects: the acceleration measured at the tool pole and the analysis of the impulsivity, using the crest factor. The signals were frequency weighted using the weighting curve Wh as described in the ISO 5349-1 standard. The same source signals were also filtered by the Wh-bl filter (ISO/TS 15694), because the weighting filter Wh (unlike the Wh-bl filter) could underestimate the effect of high frequency vibration on vibration-induced finger disorders. Ten (experienced) male operators used three beater models (battery powered) in the real olive harvesting condition. High vibration total values were obtained with values never lower than 20 m(-2). Concerning the crest factor, the values ranged from 5 to more than 22. This work demonstrated that the hand held olive beaters produced high impulsive loads comparable to the industry hand held tools.


Early and late results of a protocol for simple transposition leading to an atrial switch (Mustard) repair.
Inferences: A treatment protocol for patients with simple transposition, consisting of initial balloon atrial septostomy and leading to a delayed atrial switch repair of the Mustard type, in good circumstances, results in survivorship at 1 month, 1 year, 10 years, and 20 years of 95% (95% confidence limits [CL] 90% to 97%), 90% (95% CL 84% to 94%), 83% (95% CL 74% to 90%), and 80% (95% CL 70% to 88%), respectively. Low birth weight adversely affects survivorship. Hypoxia or heart failure accounts for most deaths within the first month and before the atrial switch (Mustard) repair. Most of the few deaths late postoperatively are sudden and they appear to occur particularly in patients who have junctional rhythm. A progressive increase in the prevalence of junctional rhythm has been a risk of the atrial switch repair, and only 76%, 65%, 59%, 56%, and 53% of patients can be expected to be free of this by 1, 5, 10, 15, and 20 years after repair. Important right ventricular dysfunction late after an atrial switch repair, with its adverse affect on the patients' functional capacity, appears to be present in up to 10% of patients after the atrial switch repair, but may not be an immutable risk of this type of repair. About 90% of patients, essentially all of those who do not have right ventricular dysfunction, can be expected to be in New York Heart Association class I or II late postoperatively.


Meningococcal septicaemia: do not be reassured by normal investigations.
This paper reports a case of meningococcal septicaemia. This case shows that normal investigations may provide the unwary clinician with an unfounded reassurance when dealing with children with this serious infection.


Serum metabolic profile and metabolome genome-wide association study in chicken.
Chickens provide globally important livestock products. Understanding the genetic and molecular mechanisms underpinning chicken economic traits is crucial for improving their selective breeding. Influenced by a combination of genetic and environmental factors, metabolites are the ultimate expression of physiological processes and can provide key insights into livestock economic traits. However, the serum metabolite profile and genetic architecture of the metabolome in chickens have not been well studied. Here, comprehensive metabolome detection was performed using non-targeted LC-MS/MS on serum from a chicken advanced intercross line (AIL). In total, 7,191 metabolites were used to construct a chicken serum metabolomics dataset and to comprehensively characterize the serum metabolism of the chicken AIL population. Regulatory loci affecting metabolites were identified in a metabolome genome-wide association study (mGWAS). There were 10,061 significant SNPs associated with 253 metabolites that were widely distributed across the entire chicken genome. Many functional genes affect metabolite synthesis, metabolism, and regulation. We highlight the key roles of TDH and AASS in amino acids, and ABCB1 and CD36 in lipids. We constructed a chicken serum metabolite dataset containing 7,191 metabolites to provide a reference for future chicken metabolome characterization work. Meanwhile, we used mGWAS to analyze the genetic basis of chicken metabolic traits and metabolites and to improve chicken breeding.


Validation of the motivation scale towards Health-Oriented physical activity (EMAPS) in Spanish Population.
The aim of the present study was to examine the psychometric properties of the motivation scale towards health-oriented physical activity (EMAPS) in the Spanish Population. A sample of 808 participants (Mage = 33.90; SD = 12.91; 366 men and 440 women), participated to ensure the structural, methodological, and external correlates of EMAPS scale validation. Results of the structural stage of analyses confirmed 6 dimensions of EMAPS (i.e., intrinsic motivation, integrated regulation, identified regulation, introjected regulation, external regulation and amotivation). In conclusion, results provided evidence for the reliability and validity of the Spanish version of the EMAPS scores. Thus, this instrument may serve to provide a measure of the motivation towards health-oriented physical activity purposes in the Spanish population.


Immune gene-viral therapy with triplex efficacy mediated by oncolytic adenovirus carrying an interferon-gamma gene yields efficient antitumor activity in immunodeficient and immunocompetent mice.
Among numerous gene therapeutic strategies for cancer treatment, gene transfer by conditionally replicative adenovirus (CRAd) of interferon-gamma (IFN-gamma) may be useful because of the possibility that it will yield IFN-gamma-mediated antiangiogenesis, immune responses, and CRAd-mediated oncolysis. In this study, we constructed a human TERT promoter-mediated oncolytic adenovirus targeting telomerase-positive cancers and armed with a mouse or human IFN-gamma gene to generate novel immune gene-viral therapeutic systems, CNHK300-mIFN-gamma and CNHK300-hIFN-gamma, respectively. The systems can specifically target, replicate in, and lyse cancer cells, while sparing normal cells. The advantage of these systems is that the number of transgene copies and their expression increase markedly via viral replication within infected cancer cells, and replicated viral progeny can then infect additional cancer cells within the tumor mass. CNHK300-mIFN-gamma induced regression of xenografts in liver cancer models in both immunodeficient and immunocompetent mice by triplex mechanisms including selective oncolysis, antiangiogenesis, and immune responses. We conclude that combining immune gene therapy and oncolytic virotherapy can enhance antitumor efficacy as a result of synergism between CRAd oncolysis and transgene composite antitumor responses.


Correlates of changes in walking during the retirement transition: The Multi-Ethnic Study of Atherosclerosis.
Retirement from employment involves disruption in daily routines and has been associated with positive and negative changes in physical activity. Walking is the most common physical activity among older Americans. The factors that influence changes in walking after retirement are unknown. The study objective was to identify correlates of within-person change in recreational walking (for leisure) and transport walking (to get places) during the retirement transition among a multi-ethnic cohort of adults (N = 928) from six US communities. Correlates were measured at the individual (e.g., gender), interpersonal (e.g., social support), and community (e.g., density of walking destinations) levels at study exams between 2000 and 2012. Comparing pre- and post-retirement measures (average 4.5 years apart), 50% of participants increased recreational walking by 60 min or more per week, 31% decreased by 60 min or more per week, and 19% maintained their recreational walking. Forty-one percent of participants increased transport walking by 60 min or more per week, 40% decreased by 60 min or more per week, and 19% maintained their transport walking after retirement. Correlates differed for recreational and transport walking and for increases compared to decreases in walking. Self-rated health, chronic conditions, and perceptions of the neighborhood walking environment were associated with changes in both types of walking after retirement. Further, some correlates differed by gender and retirement age. Findings can inform the targeting of interventions to promote walking during the retirement transition.


Lipid peroxidation of isolated chylomicrons and oxidative status in plasma after intake of highly purified eicosapentaenoic or docosahexaenoic acids.
Fourteen healthy male volunteers were given two separate high-saturated-fat meals with and without the addition of 4 g highly purified ethyl esters of either eicosapentaenoic acid (EPA) (95% pure, n = 7) or docosahexaenoic acid (DHA) (90% pure, n = 7) supplied as 1-g capsules each containing 3.4 mg vitamin E. The chylomicrons were isolated 6 h after the meals, at peak concentrations of n-3 fatty acids (FA). Addition of n-3 FA with the meal caused a 10.4-fold increase in the concentration of n-3 FA in chylomicrons compared to the saturated fat meal without addition of n-3 FA. After the saturated-fat meal, the concentration of thiobarbituric acid-reactive substances (TBARS) was 327.6 +/- 34.6 nmol/mmol triacylglycerol (TAG), which increased to 1015.8 +/- 212.0 nmol/mmol TAG (P < 0.0001, n = 14) after EPA and DHA were added to the meal. There was no significant correlation between the concentrations of TBARS and vitamin E in the chylomicrons collected 6 h after the test meal. The present findings demonstrate an immediate increase in chylomicron peroxidation ex vivo provided by intake of highly purified n-3 FA. The capsular content of vitamin E was absorbed into chylomicrons, but the amount of vitamin E was apparently not sufficient to protect chylomicrons against lipid peroxidation ex vivo. Daily intake of 4 g n-3 FA either as EPA or DHA for 5 wk did not change the plasma concentration of TBARS. Although not significantly different between groups, DHA supplementation decreased total glutathione in plasma (P < 0.05) and EPA supplementation increased plasma concentration of vitamin E (P < 0.05). The other lipid-soluble and polar antioxidants in plasma remained unchanged during 5 wk of intervention with highly purified n-3 FA.


Impact of fast-track care program in laparoscopic rectal cancer surgery: a cohort-comparative study.
Fast-track care programs after surgery improve recovery and decrease the length of hospital stay and postoperative morbidity in colonic cancer. However, the true impact of these programs on morbidity rates after rectal cancer surgery remains unclear. We aimed to assess the feasibility and impact of the fast-track program on postoperative outcomes after restorative laparoscopic rectal cancer resection and temporary loop ileostomy. This single-center observational study assessed data of patients undergoing elective rectal cancer surgery during a defined period before (standard group) and after the introduction of a fast-track program (fast-track group) from a prospectively maintained database. The primary endpoint was postoperative 90-day morbidity. Secondary endpoints were 30-day morbidity, fast-track program compliance, length of hospital stay, and readmission rate. Overall, 336 patients (n = 176, standard group; n = 160, fast-track group) were assessed; there was no significant between-group difference in the patients' baseline characteristics (age, sex, body mass index, comorbidities, or neoadjuvant treatment). The protocol compliance rate was 91.4% in the fast-track group. The 90-day morbidity and mean total length of hospital stay were significantly lower in the fast-track group than in the standard group (34% vs 49%, respectively, p < 0.01 and 8.96 days vs 10.2 days, p < 0.01, respectively). There was no difference in readmission rates. Multivariate analysis revealed the fast-track program to be the only predictive factor of postoperative morbidity. Fast-track programs can be safely implemented following rectal cancer surgery to reduce the overall morbidity rate and length of hospital stay without adversely increasing the readmission rate.


Genetic analysis of live weight of local kids to promote genetic evaluations in the arid areas of Tunisia.
Goat meat production, a widely extended activity in the more arid areas of Tunisia, relies on local breeds. These breeds are well adapted to produce under harsh conditions but have a very small size and low productivity. The aim of this study was to establish the basis for future genetic evaluations to improve growth potential of this local stock. A total of 13,095 body weights and pedigree of 945 kids in the caprine herd of the Arid Areas Institute of Médenine were used. Random regression (RR) and multiple trait (MT) models were analyzed and compared. All models included effects of age and weight of dam, age, sex and type of birth of the kid, and year × month of recording, plus random direct and maternal additive genetic and permanent environmental effects. RR and MT models behave similarly, with RR showing slightly better goodness of fit. Heritability estimates for direct (ranging from 0.15 to 0.4) and maternal (0.05 to 0.3) effects showed that efficient selection for weight is feasible in this population. Estimated correlations between ages were high (> 0.8) for direct effects across all ages and low (down to 0.2) for weights taken at distant ages for maternal effects. Estimated genetic correlations between direct and maternal components revealed an antagonistic relationship, especially at early ages. Recording of at least one weight in the first month of age of the kids to evaluate the maternal capacity and a later weight to evaluate direct effects on weight is recommended for genetic evaluations under field conditions.


Race/ethnicity, language, and asthma care: findings from a 4-state survey.
Latino and African American children have poorer asthma control than non-Latino white children, but few studies examine the association among race/ethnicity, language, and specific processes of asthma care. To evaluate the association of race/ethnicity and language with the quality of asthma care. A random sample of children from birth to the age of 17 years with asthma within 4 states (California, Texas, Illinois, and Alabama) was selected for the National Asthma Survey conducted by the National Center for Health Statistics from March 1, 2003, to March 10, 2004. Parents completed a telephone survey that included measures of asthma care quality. The final sample was 1,517 children. According to parental report, only 41.4% of children had an asthma management plan and 48.5% were ever advised by a clinician to control asthma by changing the child's home and school environment. African American and Latino children with persistent asthma had lower odds of taking controller medication than non-Latino white children. In multivariate analysis adjusting for annual income, insurance, and age, Latino children with Spanish parental interview, but not African American and Latino children with English parental interview, had poorer experiences with care than white children (ever taught what to do during an attack: odds ratio, 0.4 [95% confidence interval, 0.2-0.6]; and ever advised to change child's home and school environment: odds ratio, 0.5 [95% confidence interval, 0.3-0.8]). Differences in asthma care quality and controller use persist among racial/ethnic and language groups despite similar rates of planned encounters for asthma. Improving use of controller medications and counseling on environmental modifications are important for reducing asthma disparities.


A body shape index in a small sample of Saudi adults with type 2 diabetes.
Overweight and obesity are assessed clinically using the body mass index (BMI), but the index is criticized as a crude measure of relative fat-muscle composition. The recently introduced a body shape index (ABSI) is an independent and more accurate predictor of mortality than other anthropometric measures. Describe ABSI in relation to other clinical and cardiometabolic risk factors in Saudi patients with type 2 diabetes. Cross-sectional, armed forces diabetes clinic. Demographic and clinical data were obtained from randomly sampled patients with type 2 diabetes. The t test, analysis of variance, or Chi-square test as appropriate, and contingency table analysis. The 120 patients with type 2 diabetes (60 males, 60 females) had a mean (SD) age of 52.5 (9.3) years and BMI of 31.8 (5.5). Comparisons of ABSI and ABSI mortality risk categories with clinical and cardiovascular risk factors were statistically nonsignificant. Patients with below-average BMI (z < 0) (n = 33) were more likely to have above-average ABSI (z > 0) (27.5%) than a below-average ABSI z score (17.5%). These data provide a baseline assessment useful in further studies using larger datasets to confirm whether the ABSI can prove to be clinically useful and serve as a better predictor of mortality risk in the Saudi population. These local data should be of interest to the primary care practitioner who may be thinking of applying these new measures in their primary care practice.


Multi-class diagnosis of Alzheimer's disease using cascaded three dimensional-convolutional neural network.
Dementia is a social problem in the aging society of advanced countries. Presently, 46.8 million people affected with dementia worldwide, and it may increase to 130 million by 2050. Alzheimer's disease (AD) is the most common form of dementia. The cost of care for AD patients in 2015 was 818 billion US dollars and is expected to increase intensely due to the increasing number of patients due to the aging society. It isn't easy to cure AD, but early detection is crucial. This paper proposes a multi-class classification of AD, mild cognitive impairment (MCI), and normal control (NC) subjects using three dimensional-convolutional neural network with Support Vector Machine classifier. A cross-sectional study on structural MRI data of 465 subjects, including 132 AD patients, 181 MCI, and 152 NC, is performed in this paper. The highly complex and spatial atrophy patterns of the brain related to Alzheimer's Disease and MCI are extracted from structural MRI images using cascaded layers of the three dimensional convolutional neural network. The hectic process of segmentation and further extraction of handcrafted features is eliminated. The complete image is considered for the processing, thus incorporating every region of the brain for the classification. The features extracted using four cascaded layers of three dimensional-convolutional neural network are fed into the Support Vector Machine classifier. The proposed method achieved 97.77% accuracy which outperforms state of the art, and this algorithm is a promising indicator for the diagnosis of AD.


Evidence for a PGE-receptor in the rat kidney.
A membrane preparation derived from homogenates of the rat kidney has been shown to possess a high affinity for prostaglandins of the E-series. Other prostaglandins including PGI2 had characteristic but significantly weaker binding properties. A 15-hydroxyprostaglandin dehydrogenase (PGDH) was found to be associated with the membrane fraction studied. However it was possible to distinguish between this and the "receptor" binding by kinetic studies and by the use of a new inhibitor highly specific for PGDH.


[In-vitro studies of granulocyte phagocytosis in patients with malignant tumors].
Investigations are presented about granulocyte phagocytosis with rice starch in patients with clinically curable malignant tumours and with those treated palliatively. A significantly reduced granulocyte efficiency of phagocytosis indicating a bad prognosis of the disease can be found in those patients being in the advanced tumour stage.


Bioinformatics analysis of LINC00426 expression in lung cancer and its correlation with patients' prognosis.
To investigate the expression of long noncoding RNA (lncRNA) LINC00426 (long intergenic nonprotein coding RNA 426) in non-small cell lung cancer (NSCLC) patients and its correlation with their prognosis. The expression of long noncoding RNA LINC00426 of non-small cell lung cancer (NSCLC) in The Cancer Genome Atlas (TCGA) database was screened. According to the expression level of LINC00426 in tumor tissue of NSCLC patients, the patients were divided into high and low LINC00426 expression groups. The correlation between LINC00426 expression group and the prognosis of the patient was analyzed by log-rank test. A total of 72 NSCLC patients who had undergone surgery were retrospectively included in this study. LINC00426 relative expression of tumor and normal lung tissue of the included 72 NSCLC patients were examined by real-time quantitative PCR assay. The correlation between LINC00426 expression and the patients' clinical characteristics were also evaluated. LINC00426 relative expression was not statistically different between cancer and normal tissue (P > 0.05) of NSCLC patients in the TCGA database. The amplification and deep deletion mutation of LINC00426 gene was found in 0.5% of NSCLC patients. The overall survival (OS) of the LINC00426 high expression group was significantly higher than that of the low expression group (HR = 0.81, P = 0.044), while there was no significant difference between the high and low expression group (HR = 0.97, P = 0.82) for disease-free survival (DFS). LINC0042646 expression level was elevated in 46 cases in normal lung tissue compared to the tumor tissue of the 72 NSCLC patients. LINC0042646 expression level was significantly correlated with the clinical stage (P < 0.05). Long noncoding RNA LINC00426 was downregulated in the tumor tissue of NSCLC patients and correlated with poor prognosis.


Insights into the toxicity of troclocarban to anaerobic digestion: Sludge characteristics and methane production.
Triclocarban (TCC), as the most typical antibacterial agent, is widely discovered in many ecological environment, especially in sludge. However, so far, no studies have reported the effect of TCC exposure on the properties of excess sludge. Therefore, in this study, TCC's toxicities to waste activated sludge (WAS) were analyzed by investigating the variation of physicochemical properties of sludge. It was found that TCC exposure has no effect on sludge pH, while it facilitated organic substances release from sludge, e.g. dissolved organic matter (DOM), protein and polysaccharide, which caused an increase of sludge reduction and changed the structure of functional groups and surface morphology of sludge. Moreover, we explored the effect of TCC on anaerobic digestion of WAS and found methane production was seriously inhibited by TCC. The related mechanism tests had illustrated that TCC exposure did not affect the hydrolysis process, but promoted the acidification and acetogenesis, and importantly inhibited the methanogenesis process. Methanogenic community was further evaluated and observed that the presence of TCC could vary the microbial community of methanogens with the abundance of aceticlastic methanogens increasing and hydrogenotrophic methanogens decreasing. These findings reached in this study would widen the understanding scope for TCC's toxicity to WAS.


A hip analysis protocol for pediatric bone densitometry: the Iowa Bone Development Study.
Pediatric proximal femur dual-energy X-ray absorptiometry (DXA) scans present analytic challenges because of the lack of standard points of reference in the growing skeleton. The Iowa Bone Development Study (IBDS) developed a modified pediatric-specific proximal femur analysis protocol using Hologic software. Serial DXA measurements were obtained for 214 children at approximate ages 5, 8, 11, and 13 yr. Standard analysis procedures as described by the manufacturer (Hologic default) were compared with the IBDS protocol. The IBDS protocol yielded lower but more stable results for bone area, bone mineral content (BMC), and bone mineral density for total hip, femoral neck, trochanter, and intertrochanter as a result of more precisely controlling the regions of interest. Linear regression models with body size, age, and gender as predictors were developed to examine variation in measurements. Coefficients of determination (R(2)) with the IBDS protocol were greater for each time point, demonstrating that the modified protocol was better aligned with body size. Similarly, Spearman correlation coefficients between total hip and hip subregions were consistently higher for BMC and bone area with the IBDS protocol with differences more notable among younger children. The IBDS protocol provides a reproducible method for evaluating pediatric proximal femur DXA scans during growth.


Effect of external K on the block of the inward rectifier during hyperpolarization in guinea-pig ventricular myocytes by external Na.
The effect of changes of the external K concentration on the block of the inward-rectifying K current during hyperpolarization in guinea-pig ventricular myocytes by external Na was investigated. The voltage-dependent block of iK1 by external Na ions is decreased when the external K concentration is lowered between 5.4 and 0.54 mM, but is not influenced when Ko is increased from 5.4 to 27 mM. The effect of lowering Ko can be described as a decrease of the rate of entry of blocking Na ions at lower external K.


Elective Tracheal Intubation With the VieScope-A Prospective Randomized Non-inferiority Pilot Study (VieScOP-Trial).
Tracheal intubation is commonly performed after direct laryngoscopy using Macintosh laryngoscopes (MacL), but visualization of the larynx may be inadequate. The VieScope (VSC) as a new type of laryngoscope consisting of a straight, shielded, illuminated tube used to perform intubation via a bougie was investigated in this prospective randomized trial in patients without expected difficult airways. With ethics approval, 2 × 29 patients for elective surgery were randomized 1:1 to intubation with VSC or MacL. Endpoints were first attempt success rates (FAS), Percentage of Glottis Opening Scale (POGO), time to intubation (TTI), and difficulty ratings on visual analog scales (0-100, lower values better). Data are given as mean ± standard deviation. The FAS was 83 ± 38% for VSC and 86 ± 34% for MacL (P = 0.723). For VSC, POGO was 86 ± 17% and for MacL 68 ± 30% (P = 0.007). TTI for VSC was 93 ± 67s vs. 38 ± 17 for MacL (P < 0.001). Difficulty of intubation was rated 23 ± 22 for VSC vs. 18 ± 22 for MacL (P = 0.422), viewing conditions 12 ± 15 vs. 24 ± 25 (P = 0.031), and difficulty of tube placement was rated 27 ± 30 vs. 7 ± 8 (P = 0.001). No difference in FAS was detected between VSC and MacL. Visualization of the larynx was superior using the VSC, while TTI was prolonged and tube placement via bougie was more challenging. The VSC could be an alternative to MacL in patients with difficult laryngoscopy, but this should be investigated further in patients with expected difficult airways.


The Arabidopsis metacaspase9 degradome.
Metacaspases are distant relatives of the metazoan caspases, found in plants, fungi, and protists. However, in contrast with caspases, information about the physiological substrates of metacaspases is still scarce. By means of N-terminal combined fractional diagonal chromatography, the physiological substrates of metacaspase9 (MC9; AT5G04200) were identified in young seedlings of Arabidopsis thaliana on the proteome-wide level, providing additional insight into MC9 cleavage specificity and revealing a previously unknown preference for acidic residues at the substrate prime site position P1'. The functionalities of the identified MC9 substrates hinted at metacaspase functions other than those related to cell death. These results allowed us to resolve the substrate specificity of MC9 in more detail and indicated that the activity of phosphoenolpyruvate carboxykinase 1 (AT4G37870), a key enzyme in gluconeogenesis, is enhanced upon MC9-dependent proteolysis.


Spectrum and environmental risks of residual pharmaceuticals in stream water with emphasis on its relation to epidemic infectious disease and anthropogenic activity in watershed.
Pharmaceuticals vastly consumed by modern human for health and food might track anthropogenic impacts on aquatic ecosystem via their wide residual spectrum. This study investigated the spectrum of pharmaceutical residuals in stream water at confluence point of each subwatershed with various land use pattern in Jiulong River watershed, southeastern China. Stream water was sampled in both wet and dry seasons of 2016. Results showed that 59 out of the selected 94 compounds from 6 pharmaceutical categories were quantified among these stream water samples, up to 1488 ng L-1 for caffeine (CAF). Antibiotics and central nervous system drugs (CNs) collectively dominated the quantified instream pharmaceutical residuals. Outbreaks of epidemic infectious diseases for human and livestock partially but significantly matched seasonality of instream pharmaceutical residuals. Anthropogenic impact as land use composition of subwatersheds was significant on instream pharmaceutical loadings, especially urban land use. Cocktail risk of instream pharmaceutical residuals to aquatic organisms was assessed ranging from low to medium among the subwatersheds except high risk for the W-01 subwatershed in the dry season. Evidence from this study indicated that seasonality and wide spectrum of instream pharmaceutical residual determination could reveal anthropogenic impacts to aquatic ecosystem, such as epidemic disease and land use.


Characteristics of histamine release from isolated rat mast cells: differences when various ligands are used to induce secretion.
Differences are reported in the response of rat peritoneal mast cells to three releasing agents: ovalbumin, to which the rats were actively sensitized, anti-IgE, an immunoglobulin directed against the rat IgE molecule, and IgE chemically dimerized with suberimidate. Both the rate of histamine release and the rate of desensitization were measured for each of the three ligands. The calculated doubling times for the rates of histamine release due to ovalbumin, anti-IgE and dimer were 19.6 sec, 168 sec and 37.7 sec respectively. The calculated half-lives for the rate of desensitization due to ovalbumin, anti-IgE and dimer were 348 sec, 5900 sec and 3450 sec respectively. The three ligands are all believed to act by crosslinking Fc receptors on the cell surface but the pattern of responses obtained varied with the ligand used. It is proposed that some component of the transduction mechanism linking the stimulus to the cell to the subsequent response can distinguish between the various sizes or conformations of Fc receptor aggregates formed on the cell surface.


Hair loss as a result of cutaneous autoimmunity: frontiers in the immunopathogenesis of primary cicatricial alopecia.
Primary cicatricial alopecias (PCA) represent uncommon inflammatory disorders that result in permanent loss of scalp hair. Cutaneous autoimmunity, most prominently chronic cutaneous lupus erythematosus (CCLE), can result in this kind of scarring hair loss. The cosmetic disfigurement caused by PCA and the very unsatisfactory therapeutic options available to date all demand a better understanding of the obscure pathobiology of PCA so as to define new therapeutic targets and strategies. Hair follicle (HF) cycling and regeneration are abolished in PCA due to irreversible, epithelial hair follicle stem cell (eHFSC) damage, triggered by major, yet unclear pro-inflammatory events (e.g. type I interferon-associated cytotoxic inflammation, loss of HF immune privilege, loss of immunosuppressive "no danger" signals). Therefore, immuno-protection of eHFSC and restitution of their immune privilege are attractive future therapeutic strategies in PCA. Chronic cutaneous lupus erythematosus-associated PCA may serve as a model system for other diseases where epithelial stem cells undergo immuno-destruction.