Broadband high-sensitivity current-sensing device utilizing nonlinear magnetoelectric medium and nanocrystalline flux concentrator.
A broadband current-sensing device with frequency-conversion mechanism consisting of Terfenol-D/Pb(Zr.Ti)O3 (PZT)/Terfenol-D magnetoelectric laminate and Fe73.5Cu1Nb3Si13.5B9 nanocrystalline flux concentrator is fabricated and characterized. For the purpose of acquiring resonance-enhanced sensitivity within broad bandwidth, a frequency-modulation mechanism is introduced into the presented device through the nonlinearity of field-dependence giant magnetostrictive materials. The presented configuration provides a solution to monitor the weak currents and achieves resonance-enhanced sensitivity of 178.4 mV/A at power-line frequency, which exhibits ∼3.86 times higher than that of direct output at power-line frequency of 50 Hz. Experimental results demonstrate that a weak step-change input current of 1 mA can be clearly distinguished by the output amplitude or phase. This miniature current-sensing device provides a promising application in power-line weak current measurement.


Application of multivariate single-step SNP best linear unbiased predictor model and revised SNP list for genomic evaluation of dairy cattle in Australia.
The objectives of this study were (1) to evaluate the computational feasibility of the multitrait test-day single-step SNP-BLUP (ssSNP-BLUP) model using phenotypic records of genotyped and nongenotyped animals, and (2) to compare accuracies (coefficient of determination; R2) and bias of genomic estimated breeding values (GEBV) and de-regressed proofs as response variables in 3 Australian dairy cattle breeds (i.e., Holstein, Jersey, and Red breeds). Additive genomic random regression coefficients for milk, fat, protein yield and somatic cell score were predicted in the first, second, and third lactation. The predicted coefficients were used to derive 305-d GEBV and were compared with the traditional parent averages obtained from a BLUP model without genomic information. Cow fertility traits were evaluated from the 5-trait repeatability model (i.e., calving interval, days from calving to first service, pregnancy diagnosis, first service nonreturn rate, and lactation length). The de-regressed proofs were only for calving interval. Our results showed that ssSNP-BLUP using multitrait test-day model increased reliability and reduced bias of breeding values of young animals when compared with parent average from traditional BLUP in Australian Holsten, Jersey, and Red breeds. The use of a custom selection of approximately 46,000 SNP (custom XT SNP list) increased the reliability of GEBV compared with the results obtained using the commercial Illumina 50K chip (Illumina, San Diego, CA). The use of the second preconditioner substantially improved the convergence rate of the preconditioned conjugate gradient method, but further work is needed to improve the efficiency of the computation of the Kronecker matrix product by vector. Application of ssSNP-BLUP to multitrait random regression models is computationally feasible.


A modified eco-efficiency framework and methodology for advancing the state of practice of sustainability analysis as applied to green infrastructure.
We propose a modified eco-efficiency (EE) framework and novel sustainability analysis methodology for green infrastructure (GI) practices used in water resource management. Green infrastructure practices such as rainwater harvesting (RWH), rain gardens, porous pavements, and green roofs are emerging as viable strategies for climate change adaptation. The modified framework includes 4 economic, 11 environmental, and 3 social indicators. Using 6 indicators from the framework, at least 1 from each dimension of sustainability, we demonstrate the methodology to analyze RWH designs. We use life cycle assessment and life cycle cost assessment to calculate the sustainability indicators of 20 design configurations as Decision Management Objectives (DMOs). Five DMOs emerged as relatively more sustainable along the EE analysis Tradeoff Line, and we used Data Envelopment Analysis (DEA), a widely applied statistical approach, to quantify the modified EE measures as DMO sustainability scores. We also addressed the subjectivity and sensitivity analysis requirements of sustainability analysis, and we evaluated the performance of 10 weighting schemes that included classical DEA, equal weights, National Institute of Standards and Technology's stakeholder panel, Eco-Indicator 99, Sustainable Society Foundation's Sustainable Society Index, and 5 derived schemes. We improved upon classical DEA by applying the weighting schemes to identify sustainability scores that ranged from 0.18 to 1.0, avoiding the nonuniqueness problem and revealing the least to most sustainable DMOs. Our methodology provides a more comprehensive view of water resource management and is generally applicable to GI and industrial, environmental, and engineered systems to explore the sustainability space of alternative design configurations. Integr Environ Assess Manag 2017;13:821-831. Published 2017. This article is a US Government work and is in the public domain in the USA. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC).


Botulinum toxin injection into the lacrimal gland for treatment of proximal nasolacrimal duct obstructions in children.
The authors retrospectively evaluated the use of botulinum toxin injections to treat epiphora in children secondary to proximal obstruction of the nasolacrimal drainage system. Three patients (ages 8, 9, and 16 years) received botulinum toxin injections in the palpebral portion of the lacrimal gland. Two patients experienced symptomatic relief immediately following botulinum toxin injection. Both required subsequent injections, with an average symptomatic relief lasting 7 months. The only noted side effect was papillary conjunctivitis in one patient that resolved without treatment. The third patient was lost to follow-up. Although conjunctival dacryocystorhinostomy with Jones tube is the surgical procedure of choice for treating proximal lacrimal system obstruction, complication rates in children are high. Botulinum toxin injections provide a safe and effective alternative.


Thermoresponsive Reflective Scattering of Meso-Scale Phase Separation Structures of Uniaxially Orientation-Ordered Liquid Crystals and Reactive Mesogens.
Polymer network liquid crystals (PNLCs) capable of thermoresponsive change in reflective scattering were fabricated using a self-organization technique called photopolymerization-induced phase separation. These PNLCs exhibit nonscattering states at temperatures τ below the nematic-to-isotropic (NI) phase transition temperature τNI but reflective scattering states at τ values above τNI. The magnitude of change of optical clarity is 80% and of solar transmittance is 20% in PNLCs with a thickness of 50 μm. The microscopic structures consist of wavelength- or meso-scale phase separation domains of liquid crystals (LCs) and polymerized reactive mesogens (RMs) in which cyanobiphenyl (CB) groups are thermoresponsively transformed between uniaxially orientation-co-ordered and disordered states. Such thermoresponsive structures were fabricated by employing the CB groups as mesogenic bodies, which were expected to mutually associate due to their physicochemical structures. Cross-linkers stabilized the meso-scale domains and made the PNLCs durable through repeated temperature changes. Polarizing optical microscopy (POM) and scanning electron microscopy showed meso-scale composites that reflectively scatter visible and near-infrared light. POM and Fourier-transform infrared spectroscopy at different temperatures suggest that the orientation order of the CB groups changes in the LC phase in response to temperature but remains ordered in the RM phase. Such a thermoresponsive change in the orientation order produces the switchability in meso-scale nonuniformity and consequently in reflective light scattering. The thermoresponsive PNLCs are not only effective as energy-saving smart windows but also advantageous at stages of manufacture, installation, and operation.


[Isolation, identification and biodegradation characteristics of A new bacterial strain degrading BTEX].
A bacterial strain, able to efficiently degrade benzene, toluene, ethyl benzene, and o-xylene ( BTEX) compounds, was isolated by acclimating and enriching the activated sludge from the aeration tank in refinery wastewater treatment plant using BTEX as the sole carbon source. Based on the morphological characteristics, physiological and biochemical characteristics, sequence analysis of 16S rDNA,and Biolog identification system,the isolate was identified as Mycobacterium cosmeticum which was a newly discovered species able to degrade BTEX. The optimal conditions for the growth of the strain were at 30 degrees C and pH 7.0. The order of BTEX degradation by this isolate is benzene,toluene, ethyl benzene,and o-xylene. The specific oxygen utilization rates (SOUR) of the strain degrading benzene,toluene, ethyl benzene, and o-xylene were 165.3, 170.5, 49.3 and 57.4 mg x (min x mg)(-1), respectively. The degrading process of the strain followed the Haldane kinetic model. The maximum specific degradation rate degrading benzene, toluene, ethyl benzene,and o-xylene were 0.518, 0.491, 0.443 and 0.422 h(-1), respectively. Accordingly,the maximum specific growth rate 0.352, 0.278, 0.172 and 0.136 h(-1), respectively.


Individual motor unit analysis in the diagnosis of disorders of urethral sphincter innervation.
A technique is described for recording the electromyographic activity of striated muscle in the urethral sphincter. Using a concentric needle electrode and an oscilloscope with a delay line and trigger, individual motor units were isolated and measured. To validate the method as a means of detecting pathology, the results are presented of analysis of the motor units of a group of patients with disturbances of micturition, known to have either cauda equina lesions or pelvic nerve injury. These results are compared with those from a group of controls. In the control group 93% of the motor units were less than 6 ms in duration and 2.0 mv in amplitude. Of motor units recorded from patients with cauda equina or pelvic nerve injury 59% exceeded the control ranges for amplitude or duration. It is concluded that quantitative analysis of individual motor units may be a helpful technique in the investigation of patients with disorders of micturition.


Applications of genetic code expansion technology in eukaryotes.
Unnatural amino acids (UAAs) have gained significant attention in protein engineering and drug development owing to their ability to introduce new chemical functionalities to proteins. In eukaryotes, genetic code expansion (GCE) enables the incorporation of UAAs and facilitates posttranscriptional modification (PTM), which is not feasible in prokaryotic systems. GCE is also a powerful tool for cell or animal imaging, the monitoring of protein interactions in target cells, drug development, and switch regulation. Therefore, there is keen interest in utilizing GCE in eukaryotic systems. This review provides an overview of the application of GCE in eukaryotic systems and discusses current challenges that need to be addressed.


Mitochondrial phylogeography and molecular evolution of the rhodopsin visual pigment in troglobitic populations of Astyanax mexicanus (De Filippi, 1853).
Cave-adapted animals provide a unique opportunity to study the evolutionary mechanisms underlying phenotypic, metabolic, behavioral, and genetic evolution in response to cave environments. The Mexican tetra ( Astyanax mexicanus) is considered a unique model system as it shows both surface and cave-dwelling morphs. To date, at least 33 different cave populations have been identified, with phylogenetic studies suggesting an origin from at least two independent surface lineages, thereby providing a unique opportunity to study parallel evolution. In the present study, we carried out the most exhaustive phylogeographic study of A. mexicanus to date, including cave and surface localities, using two mitochondrial markers (cytochrome b (cyt b) and cytochrome c oxidase subunit I ( COI)) and nuclear rhodopsin visual pigment ( rho). Additionally, we inferred the molecular evolution of rho within the two contrasting environments (cave and surface) and across three geographic regions (Sierra de El Abra, Sierra de Guatemala, and Micos). In total, 267 individuals were sequenced for the two mitochondrial fragments and 268 individuals were sequenced for the rho visual pigment from 22 cave and 46 surface populations. Phylogeographic results based on the mitochondrial data supported the two-lineage hypothesis, except for the Pachón and Chica caves, whose introgression has been largely documented. The Sierra de El Abra region depicted the largest genetic diversity, followed by the Sierra de Guatemala region. Regarding the phylogeographic patterns of rho, we recovered exclusive haplogroups for the Sierra de El Abra (Haplogroup I) and Sierra de Guatemala regions (Haplogroup IV). Moreover, a 544 bp deletion in the rho gene was observed in the Escondido cave population from Sierra de Guatemala, reducing the protein from seven to three intramembrane domains. This change may produce a loss-of-function (LOF) but requires further investigation. Regarding nonsynonymous ( dN) and synonymous ( dS) substitution rates (omega values ω), our results revealed the prevailing influence of purifying selection upon the rho pigment for both cave and surface populations (ω<1), but relaxation at the El Abra region. Notably, in contrast to the other two regions, we observed an increase in the number of dN mutations for Sierra de El Abra. However, given that a LOF was exclusively identified in the Sierra de Guatemala region, we cannot dismiss the possibility of a pleiotropic effect on the Rho protein.


Computed tomography of renal metastases.
The CT manifestations of renal metastases from nonurinary tract carcinomas were evaluated in five autopsy-proven cases. Three cases resembled renal inflammatory disease or renal cysts. The wide variety of CT manifestations of renal metastases underscores the need to bear renal metastases in mind when renal abnormalities are observed in any case of advanced malignancy.


Treatment with the PI3K inhibitor buparlisib (NVP-BKM120) suppresses the growth of established patient-derived GBM xenografts and prolongs survival in nude rats.
Glioblastomas (GBMs) are aggressive brain tumours with a dismal prognosis, despite combined surgery, radio- and chemotherapy. Close to 90 % of all GBMs harbour a deregulated PI3K pathway, which is essential in regulating central cellular functions such as proliferation, cell growth, motility and survival. Thus, PI3K represents a potential target for molecular therapy in GBM. We investigated the anti-tumour efficacy of the PI3K inhibitor buparlisib (NVP-BKM120) in GBM cell lines in vitro and in vivo, when treatment was initiated after MRI-confirmed tumour engraftment. We found that buparlisib inhibited glioma cell proliferation in a dose dependent manner, demonstrated by MTS assay, manual cell count and BrdU incorporation. A dose dependent increase in apoptosis was observed through flow cytometric analysis. Furthermore, by immunocytochemistry and western blot, we found a dose dependent inhibition of Akt phosphorylation. Moreover, buparlisib prolonged survival of nude rats harboring human GBM xenografts in three independent studies and reduced the tumours' volumetric increase, as determined by MRI. In addition, histological analyses of xenograft rat brains showed necrotic areas and change in tumour cell nuclei in buparlisib-treated animals. The rats receiving buparlisib maintained their weight, activity level and food- and water intake. In conclusion, buparlisib effectively inhibits glioma cell proliferation in vitro and growth of human GBM xenografts in nude rats. Moreover, the compound is well tolerated when administered at doses providing anti-tumour efficacy. Thus, buparlisib may have a future role in glioma therapy, and further studies are warranted to validate this compound for human use.


12-step affiliation and attendance following treatment for comorbid substance dependence and depression: a latent growth curve mediation model.
Among substance-dependent individuals, comorbid major depressive disorder (MDD) is associated with greater severity and poorer treatment outcomes, but little research has examined mediators of posttreatment substance use outcomes within this population. Using latent growth curve models, the authors tested relationships between individual rates of change in 12-step involvement and substance use, utilizing posttreatment follow-up data from a trial of group Twelve-Step Facilitation (TSF) and integrated cognitive-behavioral therapy (ICBT) for veterans with substance dependence and MDD. Although TSF patients were higher on 12-step affiliation and meeting attendance at end-of-treatment as compared with ICBT, they also experienced significantly greater reductions in these variables during the year following treatment, ending at similar levels as ICBT. Veterans in TSF also had significantly greater increases in drinking frequency during follow-up, and this group difference was mediated by their greater reductions in 12-step affiliation and meeting attendance. Patients with comorbid depression appear to have difficulty sustaining high levels of 12-step involvement after the conclusion of formal 12-step interventions, which predicts poorer drinking outcomes over time. Modifications to TSF and other formal 12-step protocols or continued therapeutic contact may be necessary to sustain 12-step involvement and reduced drinking for patients with substance dependence and MDD.


Urine Lipoarabinomannan Testing in Adults With Advanced Human Immunodeficiency Virus in a Trial of Empiric Tuberculosis Therapy.
The urine lipoarabinomannan (LAM) antigen test is a tuberculosis (TB) diagnostic test with highest sensitivity in individuals with advanced human immunodeficiency virus (HIV). Its role in TB diagnostic algorithms for HIV-positive outpatients remains unclear. The AIDS Clinical Trials Group (ACTG) A5274 trial demonstrated that empiric TB therapy did not improve 24-week survival compared to isoniazid preventive therapy (IPT) in TB screen-negative HIV-positive adults initiating antiretroviral therapy with CD4 counts <50 cells/µL. Retrospective LAM testing was performed on stored urine obtained at baseline. We determined the proportion of LAM-positive participants and conducted modified intent-to-treat analysis excluding LAM-positive participants to determine the effect on 24-week survival, TB incidence, and time to TB using Kaplan-Meier method. A5274 enrolled 850 participants; 53% were male and the median CD4 count was 18 (interquartile range, 9-32) cells/µL. Of the 850, 566 (67%) had LAM testing (283 per arm); 28 (5%) were positive (21 [7%] and 7 [2%] in the empiric and IPT arms, respectively). Of those LAM-positive, 1 participant in each arm died and 5 of 21 and 0 of 7 in empiric and IPT arms, respectively, developed TB. After excluding these 28 cases, there were 19 and 21 deaths in the empiric and IPT arms, respectively (P = .88). TB incidence remained higher (4.6% vs 2%, P = .04) and time to TB remained faster in the empiric arm (P = .04). Among outpatients with advanced HIV who screened negative for TB by clinical symptoms, microscopy, and Xpert testing, LAM testing identified an additional 5% of individuals with TB. Positive LAM results did not change mortality or TB incidence.


[Development of immunoassay for cytokines and its clinical significance].
As measurement systems of cytokines have recently been developed, there are many reports indicating the relationship between cytokines and various diseases. We have also developed various new measurement systems using gene technology and hybridoma technology. The measurement system is composed of the following 5 steps. (1) Cloning of cytokines, (2) Expression of cytokines, (3) Purification of cytokines, (4) Preparation of antibodies (monoclonal and polyclonal antibodies), (5) Development of immunoassay. Cytokines are measured not only in the cytokine itself but also in the receptor, receptor antagonist, and autoantibody. We established the measurement system of cytokines using ELISA (antibody is labeled by enzyme.) for the cytokine itself and RIA (antigen is labeled by isotope.) for the autoantibody to cytokines. The blood concentration of cytokines is low because cytokines are utilized immediately after production and excreted into the urine. Therefore, the immunological responses of individuals can be determined by an ex vivo measurement of the production of cytokines by stimulation of whole blood with LPS not by simply measuring the cytokine itself in plasma. We call this method "Whole Blood Induction Method". This method is positioned as one of the methods which shows the immunological response of cytokines to the outer body at the time of infection using a low volume of human blood. Finally, studies of cytokines have been carried out not only in immunological systems but also in hormone systems which are closely related to cytokines. Studies have also expanded to fields which, to date, have not been thought to be related by investigating adherence factors.(ABSTRACT TRUNCATED AT 250 WORDS)


The activity of a yeast Family 16 methyltransferase, Efm2, is affected by a conserved tryptophan and its N-terminal region.
The Family 16 methyltransferases are a group of eukaryotic nonhistone protein methyltransferases. Sixteen of these have recently been described in yeast and human, but little is known about their sequence and structural features. Here we investigate one of these methyltransferases, Saccharomyces cerevisiae elongation factor methyltransferase 2 (Efm2), by site-directed mutagenesis and truncation. We show that an active site-associated tryptophan, invariant in Family 16 methyltransferases and at position 222 in Efm2, is important for methyltransferase activity. A second highly conserved tryptophan, at position 318 in Efm2, is likely involved in S-adenosyl methionine binding but is of lesser consequence for catalysis. By truncation analysis, we show that the N-terminal 50-200 amino acids of Efm2 are critical for its methyltransferase activity. As N-terminal regions are variable among Family 16 methyltransferases, this suggests a possible role in determining substrate specificity. This is consistent with recently solved structures that show the core of Family 16 methyltransferases to be near-identical but the N termini to be structurally quite different. Finally, we show that Efm2 can exist as an oligomer but that its N terminus is not necessary for oligomerisation to occur.


Anaplastic large cell lymphoma of T-cell phenotype in acquired immunodeficiency syndrome.
Anaplastic large cell lymphoma (ALCL) is an uncommon non-Hodgkin's lymphoma in the general population as well as in HIV-infected patients. Ordinarily, ALCL expresses T-cell phenotype, but lymphoproliferative disorders derived from T cells rarely occur in acquired immunodeficiency syndrome (AIDS). We describe a white male homosexual with AIDS who had bilateral pleural effusions. Examination of the pleural fluid revealed ALCL positive for Ki-1 (CD30), LCA (CD45), UCHL-1 (CD45RO), CD43, CD3, and epithelial membrane antigen. The lymphoma was negative for the B-cell marker L26 (CD20) and for Leu-M1 (CD15). The T-cell origin was also confirmed by the monoclonal rearrangement of the T-cell receptor beta chain gene. A review of other cases of ALCL in HIV-positive individuals shows variability in clinical presentation and biologic behavior of this lymphoma type. It also points to the potential contribution of gene rearrangement studies for recognition of phenotype. In addition, the role of determination of the presence of t(2;5) and the corresponding gene product is discussed.


Patient ventilator interfaces: practical aspects in the chronic situation.
In the ventilator-dependent patient, the nonpsychological problems of the chronic phase relate mainly to aspects of the patient ventilator interface. Humidification, suctioning of secretions, and ventilatory circuit and monitoring are the three most important aspects to which careful attention is needed. Good humidification can be obtained by means of various devices, which can provide humidity directly or indirectly: in the tracheostomized patient, the heat and moisture exchanger appears to be a good method because of its antibacterial properties. Airway suctioning is frequently needed in patients receiving ventilation invasively. Suctioning of secretions might possibly be associated with the risk of major cardiorespiratory complications: bacterial colonization of the airways and the subsequent increased risk of infection should be carefully considered. Problems concerning the ventilatory circuit and monitoring can be specific in patients with a tracheal cannula and those with a nasal/facial interface. Long-term tracheostomy in itself represents a real risk for bacterial colonization, damage to the tracheal mucosa, and to functioning of the vocal cords (both for speech and swallowing): therefore, a switch from invasive to noninvasive ventilatory interface may be proposed. Most problems with the nasal mask interface concern air leakage and the skin mucosal lesions. Two major aspects must be taken into account when considering the long-term effects of noninvasive ventilatory support monitoring: the possible effect of CO2 rebreathing, and the inadequate volume/pressure delivery, so that proper ventilation cannot be achieved. Use of an oral/mouth interface is of limited interest in subjects with restrictive disorders: air gastric distension and orthodontic problems are the most common side-effects in chronic use.


Plasma total homocysteine: instigator or indicator of cardiovascular disease?
Cardiovascular disease (CVD) is a major cause of morbidity and mortality in developed countries. However, traditional risk factors cannot fully account for this. In the last 20 years, there has been an explosion of interest in plasma total homocysteine (tHcy) as a potential modifiable risk factor for CVD. Recent meta-analyses of epidemiological studies support the concept that increased tHcy concentrations are associated with CVD. This has led to the 'homocysteine hypothesis', which states that lowering plasma tHcy using folic acid and other B-vitamins will reduce the risk of CVD. In experimental studies, homocysteine has been shown to cause oxidative stress, endothelial cell dysfunction and promote thrombogenesis. However, data from recent large randomized controlled trials have shown that there is no clinical benefit to lowering plasma tHcy concentrations with folic acid and other B-vitamins. This lack of effect of tHcy lowering strongly suggests that homocysteine is not an instigator but merely an indicator of CVD.


A Brazilian government external individual monitoring service: experience since 1972.
Instituto de Radioproteção e Dosimetria, a Brazilian government research institute, provides individual monitoring services since 1972. Its dosemeters are: film-based thorax for whole body photons, thermoluminescence dosimetry (TLD) albedo for whole body neutrons and TLD ring for extremity photons. About 6000 radiation workers are currently being monitored with film dosemeters in 256 different facilities in Brazil, most of them working in health-related activities. Around 400 Brazilian radiation workers are monitored with TLD albedo neutron monitor and about 500 workers use TLD rings. This paper describes the monitoring systems used, presents the results obtained in internal quality programs and in intercomparison exercises and analyses the measured dose values from 1985 to 2009.


Acoustofluidics-Assisted Engineering of Multifunctional Three-Dimensional Zinc Oxide Nanoarrays.
The integration of acoustics and microfluidics (termed acoustofluidics) presents a frontier in the engineering of functional micro-/nanomaterials. Acoustofluidic techniques enable active and precise spatiotemporal control of matter, providing great potential for the design of advanced nanosystems with tunable material properties. In this work, we introduce an acoustofluidic approach for engineering multifunctional three-dimensional nanostructure arrays and demonstrate their potential in enrichment and biosensing applications. In particular, our acoustofluidic device integrates an acoustic transducer with a sharp-edge-based acoustofluidic reactor that enables uniform patterning of zinc oxide (ZnO) nanoarrays with customizable lengths, densities, diameters, and other properties. The resulting ZnO nanoarray-coated glass capillaries can rapidly and efficiently capture and enrich biomolecules with sizes ranging from a few nanometers to several hundred nanometers. In order to enable the detection of these biomolecules, silver (Ag) nanoparticles are deposited onto the ZnO nanoarrays, and the integrated ZnO-Ag capillary device functions as a label-free plasmonic biosensing system for surface-enhanced Raman spectroscopy (SERS) based detection of exosomes, DNA oligonucleotides, and E. coli bacteria. The optical sensing enhancement of ZnO-Ag capillary is further validated through finite-difference time-domain (FDTD) simulations. These findings not only provide insights into the engineering of functional micro/nanomaterials using acoustofluidics but also shed light onto the development of portable microanalytical devices for point-of-care applications.


Synthetic nanoelectronic probes for biological cells and tissues.
Research at the interface between nanoscience and biology could yield breakthroughs in fundamental science and lead to revolutionary technologies. In this review, we focus on the interfaces between nanoelectronics and biology. First, we discuss nanoscale field effect transistors (nanoFETs) as probes to study cellular systems; specifically, we describe the development of nanoFETs that are comparable in size to biological nanostructures involved in communication through synthesized nanowires. Second, we review current progress in multiplexed extracellular sensing using planar nanoFET arrays. Third, we describe the designs and implementation of three distinct nanoFETs used to perform the first intracellular electrical recording from single cells. Fourth, we present recent progress in merging electronic and biological systems at the three-dimensional tissue level by use of macro-porous nanoelectronic scaffolds. Finally, we discuss future developments in this research area, unique challenges and opportunities, and the tremendous impact these nanoFET-based technologies might have on biological and medical sciences.


Structural characteristics and growth of pentagonal silver nanorods prepared by a surfactant method.
The crystal structure and growth mechanism of silver nanorods prepared by a seed-mediated surfactant method using the cationic surfactant cetyltrimethylammonium tosylate (CTAT) and its wormlike micelles are characterized by conventional and high-resolution transmission electron microscopy. Depending on the nanorod orientations, two types of electron diffraction patterns are obtained from a truncated decahedral structure consisting of five crystal units packing along [111] twining planes with five [111] planes on each end and five circumferential [001] side surfaces parallel to a <110> longitudinal direction. High-resolution images of the nanorods and the corresponding Fourier transform patterns confirm the results from the morphological and diffraction analyses. The silver nanorods grow only from multiply twinned decahedral seeds, and the high selectivity of surfactant attachment results in a barrier to the transfer of silver atoms from the solution to the circumferential [100] planes. Blockage of circumferential growth causes the aspect ratio of the rod to grow.


The impact of strenuous physical activity on the development of pelvic organ prolapse.
Pelvic organ prolapse is a common gynaecological problem and the mechanisms underlying prolapse development are not yet clear but it is thought that increases in abdominal pressure, such as those routinely involved in heavy lifting and long periods of standing, may cause progressive pelvic floor damage over time. The aim of this study was to investigate the effects of strenuous physical activity on the development of prolapse. A narrative literature review was carried out to investigate the effects of occupation and recreational activity on the pathogenesis of pelvic organ prolapse. A marked paucity of literature relevant to the research question makes it difficult to draw firm conclusions. Further research is greatly needed to explore potentially preventable factors in this frequently occurring condition. The review reveals some evidence linking strenuous physical activity with pelvic organ prolapse but this is neither consistent nor adequately powered to reach any firm conclusions.


Stream periphytic biodegradation of the anionic surfactant C12-alkyl sulfate at environmentally relevant concentrations.
The effects of continuous exposure to C12-alkyl sulfate on a periphytic microbial community were determined in an 8-week stream mesocosm study. C12-alkyl sulfate concentrations ranged from environmentally relevant (< 10-20 micrograms/liter) to unrealistically high concentrations (> 1500 micrograms/liter). Endpoints evaluated included turnover rates, bacterial cell density, heterotrophic mixed amino acid uptake, and fatty acid profile evaluations. Predosed periphyton demonstrated a mean turnover rate for C12-alkyl sulfate of 0.08/hr. During the 8-week dosing period, a significant increase in mean turnover rates was observed in streams dosed with > or = 61 micrograms C12-alkyl sulfate/liter, despite a 10 degrees C drop in stream temperature. A significant correlation between turnover rate and C12-alkyl sulfate concentration was also observed. While bacterial cell density increased during the study, it was determined that the biodegradation acclimation to C12-alkyl sulfate was not biomass-specific. Likewise, bacterial activity generally increased over the study, but it did not correlate with either biodegradation or bacterial cell density. Lastly, phospholipid fatty acid profiles indicate that a shift in the microbial community occurred in the high-dose stream as opposed to the control stream. This study demonstrates that C12-alkyl sulfate is rapidly degraded and induces a biodegradative acclimation response at environmentally relevant concentrations.


Bending Stiffness-Directed Fabricating of Kevlar Aerogel-Confined Organic Phase-Change Fibers.
Smart and functional fibers have demonstrated great potentials in a wide range of applications including wearable devices and other high-tech fields, but design and fabrication of smart fibers with manageable structures as well as versatile functions are still a great challenge. Herein, an ingenious bending-stiffness-directed strategy is developed to fabricate smart phase-change fibers with different bending stiffnesses for diverse applications. Specifically, the hydrophobic Kevlar aerogel-confined paraffin wax fibers (PW@H-KAF) are fabricated by employing hydrophobic Kevlar aerogel fibers (H-KAFs) as the porous host and paraffin as the functional guest, where the H-KAF is obtained by applying a two-step process to functionalize Kevlar nanofibers (KNFs) with a special coagulation bath containing a mixture of ethanol and n-bromobutane. The prepared PW@H-KAFs exhibit high latent heat (135.1-172 J/g), outstanding thermal cyclic stability and satisfactory mechanical properties (30 MPa in tensile strength and 30% in tensile strain). In addition, the PW@H-KAFs with bending stiffness was lower than the critical one (1.22 × 10-9 N·m2) even in a solid state of paraffin wax exhibits high flexibility, washable performance, and high thermal management capability, showing great potential for smart temperature-regulating fabrics. PW@H-KAFs with a bending stiffness higher than the critical one at a solid state of paraffin wax can be utilized as shape memory materials, attributed to the transition between rigidity and flexibility caused by the phase transition. As a proof of concept, a dynamic gripper is designed based on the PW@H-KAF (400 μm in diameter) for transporting items by gripping in the rigid state and releasing in the flexible state. This work realizes versatile applications with the PW@H-KAFs through the bending stiffness-directed method, providing ideas for the application of phase-change composites.


Management of carbon tetrachloride-induced acute liver injury in rats by syngeneic hepatocyte transplantation in spleen and peritoneal cavity.
Acute hepatitis may seldom have a fulminant course. In the treatment of this medical emergency, potential liver support measure must provide immediate and sufficient assistance to the hepatic function. The goal of our study was to study the adequacy of hepatocyte transplantation (HCTx) in two different anatomical sites, splenic parenchyma and peritoneal cavity, in a rat model of reversible acute hepatitis induced by carbon tetrachloride (CCl(4)). After CCl(4) intoxication, 84 male Wistar rats used as recipients were divided in to four experimental groups accordingly to their treatment: Group A (n=24): intrasplenic transplantation of 10x10(6) isolated hepatocytes, Group B (n=24): intraperitoneal transplantation of 20x10(6) isolated hepatocytes attached on plastic microcarriers, Group C (n=18): intrasplenic injection of 1 mL normal saline (sham-operated controls), Group D (n=18): intraperitoneal injection of 2.5 mL normal saline (sham-operated controls). Survival, liver function tests (LFT) and histology were studied in all four groups, on d 2,5 and 10 post-HCTx. The ten-day survival (and mean survival) in the 4 groups was 72.2% (8.1+/-3.1), 33.3% (5.4+/-3.4), 0% (3.1+/-1.3) and 33.3% (5.4+/-3.6) in groups A, B, C, D, respectively (P(AB)<0.05, P(AC)<0.05, PBD=NS). In the final survivors, LFT (except alkaline phosphatase) and hepatic histology returned to normal, independently of their previous therapy. Viable hepatocytes were identified within splenic parenchyma (in group A on d 2) and both in the native liver and the fatty tissue of abdominal wall (in group B on d 5). A significantly better survival of the intrasplenically transplanted animals has been demonstrated. Intraperitoneal hepatocytes failed to promptly engraft. A different timing between liver injury and intraperitoneal HCTx may give better results and merits further investigation.


Prehospital Systolic Hypertension and Outcomes in Patients with Spontaneous Intracerebral Hemorrhage.
It is well known that hematoma volume and expansion is associated with poor outcomes in patients with spontaneous intracerebral hemorrhage (sICH). The factors associated with hematoma volume and possible expansion include the use of anticoagulant medications, autoimmune or bacterial diseases that reduce platelet production, and genetic defects of Von Willebrand factor causing inhibition or reduction of platelet aggregation. However, little is known about the role of elevated systolic blood pressure (SBP) on hematoma volume and its ultimate role on sICH when identified in the prehospital setting. Our objectives were to determine the prevalence of elevated SBP among diagnosed sICH patients transported by emergency medical services (EMS), and to explore possible associations between prehospital elevated SBP and hematoma volume. This is a hypothesis-generating study for which we used a retrospective observational design. The subjects included 243 adult patients who were seen and treated for sICH in an emergency department serving a county hospital in a large metropolitan city. Elevated SBP in the setting of sICH was defined as ≥140 mm Hg. A univariate analysis was performed to investigate associations between patient demographics, elevated SBP, and sICH characteristics with the pre-determined outcome of hematoma volume. We then performed a multivariable logistic regression model to determine if elevated prehospital SBP remained associated with hematoma volume. The number of subjects with a hospital-based diagnosis of sICH was 243. Of those, 193 (79%) were transported by an ambulance. Among those transported by ambulance, 180 (93%) had a documented prehospital SBP; out of those patients with a documented SBP, 173 (96%) showed an elevated SBP of ≥140 mm Hg, and 82 (46%) had a hematoma volume of ≥30 mL. Our univariate analysis showed that sICH patients with an elevated prehospital SBP of ≥140 mm Hg were associated with hematoma volume. The multivariable regression model showed that elevated prehospital SBP (≥140 mm Hg) was associated with larger hematoma volumes (odds ratio (OR) 3.86 95% confidence interval (CI) 1.02-4.60). Prehospital elevated SBP is associated with larger hematoma volume in patients with sICH. Future studies should confirm these findings in a larger cohort of patients.


Six molecules of SV40 large T antigen assemble in a propeller-shaped particle around a channel.
The large T antigen of simian virus 40 (SV40) is a multifunctional regulatory protein, responsible for both the control of viral infection and the required alterations of cellular processes. T antigen is the only viral protein required for viral DNA replication. It binds specifically to the viral origin and as a helicase unwinds the SV40 DNA bidirectionally. The functional complex is a double hexameric oligomer. In the absence of DNA, but in the presence of ATP or a non-hydrolyzable analog, T antigen assembles into hexamers, which are active as a helicase when a partially single-stranded (3') entry site exists on the substrate. We have used negative staining electron microscopy, single particle image processing and three-dimensional reconstruction with a new algebraic reconstruction techniques (ART) algorithm to study the structure of these hexameric particles in the presence of different nucleotide cofactors (ATP, ADP, and the non-hydrolyzable analogs ATPgammaS and AMP-PNP). In every case a strong 6-fold structure was found, with the six density maxima arranged in a ring-like particle around a channel, and a well-defined vorticity. Because these structural features have recently been found in other prokaryotic helicases, they seem to be strongly related to the activity of the protein, which suggests a general functional model conserved through evolution.


Non-enhanced versus low-dose contrast-enhanced renal magnetic resonance angiography at 7 T: a feasibility study.
Background Considering the currently reported association between a repetitive application and cumulative dosage of Gadolinium (Gd)-based contrast agents and Gd-deposition in brain tissue as well as the risk for the advent of nephrogenic systemic fibrosis (NSF), techniques allowing for a dose reduction become an important key aspect aside from non-enhanced magnetic resonance angiography (MRA) techniques. Thus, this study was focused on the reduction and/or complete omission of contrast agent for renal MRA at 7T. Purpose To evaluate the performance of time-of-flight MRA versus low-dose contrast-enhanced (CE) renal MRA at 7T. Material and Methods Ten healthy volunteers were examined on a 7T MR system comprising a TOF MRA and three-dimensional (3D) fast low angle shot spoiled gradient-echo sequence (FLASH) MRA after administration of one-quarter of clinical dose of gadobutrol. Qualitative image analysis was performed including overall image quality, artery delineation and presence of artifacts. Contrast ratio (CR), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) of the renal arteries were calculated. Results TOF MRA and low-CE MRA achieved comparable overall ratings, with slightly superior delineation of the main renal arteries in TOF MRA (TOF = 3.10 ± 0.75, low-CE = 2.95 ± 0.75). Segmental branches outside and inside the parenchyma were delineated significantly better on TOF MRA. Quantitative analysis demonstrated the superiority of TOF MRA, yielding higher scores for CR, SNR, and CNR. Conclusion The initial results of our study demonstrate the feasibility and comparable diagnostic performance of TOF and low-dose CE renal MRA at 7T.


Recent advances in circulating tumor cells and cell-free DNA in metastatic prostate cancer: a review.
The treatment landscape of metastatic prostate cancer has changed dramatically over the past five years. As new discoveries are made and further novel therapies become available, there is a heightened urgency to develop biomarkers that can guide prognoses and predict therapy responses. Circulating tumor cells (CTCs) and cell-free circulating tumor DNA (ctDNA) in the blood have emerged as potential promising tumor avatars. Areas covered: In this review, we describe technological breakthroughs and clinical implementation of the CTCs and ctDNA. We also discuss the key challenges that must be overcome before circulating blood-based biomarkers can be universally adopted into the management of patients with metastatic prostate cancer. Expert commentary: Both CTCs and ctDNA have the potential to be incorporated into routine patient care, with increasing numbers of prospective trials incorporating them into clinical designs. CTCs and ctDNA will thus have an increasingly valuable role in augmenting our understanding of prostate cancer at a molecular level, aiding in prognostication of prostate cancer patients, acting as a surrogate for OS in clinical trials, and helping us prioritize our treatment selections by elucidating resistance mechanisms.


In vivo studies of the evolution of physical properties of the human skin with age.
In vivo measurements taken by valid methods, help to interpret the phenomena associated with the aging process. The authors developed some routine techniques to measure physical properties of the skin both deep in the dermis-epidermis and at the surface (stratum corneum). Measurements on the forearm of 150 people yielded the following results regarding the dermis-epidermis level: (1) skin thickness begins to decrease at 45 years of age for men and women, when women's skin becomes thinner than men's skin; (2) torsion extensibility, normalized for a given skin thickness, sharply decreases after 35 years of age; (3) skin optical properties are modified, ie the photoplethysmographic signal, measured on the forehead, greatly increase after 60 years of age; (4) at the cutaneous surface level, the main modifications are increased shedding of stratum corneum after 60 years of age in parallel with a modification of the stratum corneum cohesivity, altered skin microrelief during the aging process, and slightly decreased transepidermal water loss while the corneocyte projected size increases. These findings allow consideration of the aging process at the skin level as a phased process. The alterations of the physical properties and their kinetics suggest a various process according to the different cutaneous sections.


Disturbance of Fatty Acid Desaturation Mediated by FADS2 in Mesenteric Adipocytes Contributes to Chronic Inflammation of Crohn's Disease.
The aim of this study was to investigate the metabolic profile of mesenteric adipocytes and the correlations between key metabolic changes and local inflammation in the context of Crohn's disease [CD]. Metabolic dysfunction was shown to be regulated by fatty acid desaturase-2 [FADS2], through metabolomics and functional analyses of mesenteric adipose tissue biopsies and primary mesenteric adipocytes isolated from surgical specimens collected from CD patients and control subjects. FADS2 was overexpressed in vitro and in vivo using a lentiviral vector and an adeno-associated virus [AAV], respectively. The interaction between mesenteric adipocytes and inflammation responses was evaluated by establishing a cell coculture system and a FADS2-AAV treated animal model; 3T3-L1 cells were used to elucidate the mechanism underlying FADS2 deregulation. We observed significant changes in the levels of metabolites involved in the multi-step synthesis of long-chain polyunsaturated fatty acids [PUFAs]. Gas chromatography analysis revealed impaired desaturation fluxes towards the n-6 and n-3 pathways, which are associated with reduced FADS2 activity in human mesentery tissue. Decreased FADS2 expression at both mRNA and protein levels was confirmed in surgical specimens. The restoration of FADS2 expression, which allows for the endogenous conversion of n-3 fatty acids into proresolving lipid mediators, resulted in a significant reduction in pro-inflammatory macrophage infiltration and attenuated expression of inflammatory cytokines or adipokines. These findings indicate that impaired fatty acid desaturation and lipid mediator imbalance within mesenteric adipose tissue contributes to chronic inflammation in CD. The therapeutic role of FADS2 may lead to improved CD treatment.


[Effect of PSK on the recovery of macrophage function in tumor-bearing mice].
Chemotactic response of macrophage to PHA was depressed at early stages in allogeneic sarcoma 180-bearing ICR mice and syngeneic X5563-bearing C3H/He mice and their depressed response were restored to the normal levels by PSK. Macrophages-dependent resistance against Listeria monocytogenes at early phase of infection was depressed at the early stage after tumor inoculation. The depressed resistance was restored by PSK in X5563-bearing mice and by a combination of tumor resection and PSK in sarcoma 180-bearing mice.


Bovine Immunoinhibitory Receptors Contribute to Suppression of Mycobacterium avium subsp. paratuberculosis-Specific T-Cell Responses.
Johne's disease (paratuberculosis) is a chronic enteritis in cattle that is caused by intracellular infection with Mycobacterium avium subsp. paratuberculosis. This infection is characterized by the functional exhaustion of T-cell responses to M. avium subsp. paratuberculosis antigens during late subclinical and clinical stages, presumably facilitating the persistence of this bacterium and the formation of clinical lesions. However, the mechanisms underlying T-cell exhaustion in Johne's disease are poorly understood. Thus, we performed expression and functional analyses of the immunoinhibitory molecules programmed death-1 (PD-1)/PD-ligand 1 (PD-L1) and lymphocyte activation gene 3 (LAG-3)/major histocompatibility complex class II (MHC-II) in M. avium subsp. paratuberculosis-infected cattle during the late subclinical stage. Flow cytometric analyses revealed the upregulation of PD-1 and LAG-3 in T cells in infected animals, which suffered progressive suppression of interferon gamma (IFN-γ) responses to the M. avium subsp. paratuberculosis antigen. In addition, PD-L1 and MHC-II were expressed on macrophages from infected animals, consistent with PD-1 and LAG-3 pathways contributing to the suppression of IFN-γ responses during the subclinical stages of M. avium subsp. paratuberculosis infection. Furthermore, dual blockade of PD-L1 and LAG-3 enhanced M. avium subsp. paratuberculosis-specific IFN-γ responses in blood from infected animals, and in vitro LAG-3 blockade enhanced IFN-γ production from M. avium subsp. paratuberculosis-specific CD4(+) and CD8(+) T cells. Taken together, the present data indicate that M. avium subsp. paratuberculosis-specific T-cell exhaustion is in part mediated by PD-1/PD-L1 and LAG-3/MHC-II interactions and that LAG-3 is a molecular target for the control of M. avium subsp. paratuberculosis-specific T-cell responses.


Investigation of first mirror heating for the collective Thomson scattering diagnostic in ITER.
Collective Thomson scattering (CTS) has the capabilities to measure phase space densities of fast ion populations in ITER resolved in configuration space, in velocity space, and in time. In the CTS system proposed for ITER, probing radiation at 60 GHz generated by two 1 MW gyrotrons is scattered in the plasma and collected by arrays of receivers. The transmission lines from the gyrotrons to the plasma and from the plasma to the receivers contain several quasioptical mirrors among other components. These are designed to produce astigmatic beam patterns in the plasma where the beam shapes will have a direct impact on the signal strength of the diagnostic, the spatial resolution, and the robustness of probe and receiver beam overlap against density excursions. The first mirror has a line of sight to the plasma and is thus exposed to severe neutron streaming. The present neutronics and thermomechanical modeling of a first mirror on the high field side indicates that the mirror curvature may warp due to heating. This may alter the beam quality, and therefore, thermal effects have to be accounted for during the design of the mirror. The modeling further demonstrates that thin mirrors are superior to thick mirrors from a thermomechanical point of view.


Gamma-endorphin affects retrieval of an inhibitory avoidance task.
Rats were trained in a step-down inhibitory avoidance task and retrieval was measured during a test session conducted 24 h after training. The ip administration of a low dose of gamma-endorphin (0.2 micrograms/kg) immediately after training reduced retrieval time from 40.6 to 13.5 s (N = 15). Higher doses of gamma-endorphin given 5 min before testing (1.0 micrograms/kg) or immediately after training (5 micrograms/kg) enhanced retrieval time from 38.6 to 300 s (N = 15) and from 40.6 to 104.4 s (N = 15). All of these effects were blocked by pretreatment with naloxone (0.4 mg/kg). Alpha-endorphin (0.2, 1.0 or 5.0 micrograms/kg) administered either after training or before testing had no effect on retrieval. Since at least the amnestic effect of gamma-endorphin is similar to that of beta-endorphin, and gamma-endorphin is a possible metabolite of beta-endorphin by limited proteolysis of the carboxyl-terminal amino acid, it is suggested that at least some effects of beta-endorphin on memory may be mediated by its proteolysis product, gamma-endorphin.


Textile dyeing wastewater treatment in a sequencing batch reactor system.
This study was undertaken to examine the feasibility of treating biologically textile wastewater for organic carbon removal. The study was conducted over a lab scale SBR equipped with an in-house developed data acquisition and control software. From monitored operation of SBR and dissolved oxygen values, together with a simple compressed air ON/OFF control scheme, on-line Oxygen Uptake Rate (OUR) profiles during aerobic reaction periods were obtained. Due to the high variability of wastewater characteristics, periodical analyses of textile wastewater were conducted and thus characterized for pH, conductivity, total and volatile solids, COD, ammonia, and TKN. After an initial period of activated sludge adaptation to textile wastewater, the SBR was operated at step-feed strategy to reduce the effluent biodegradable matter presents in the wastewater by SBR water change ratio modification and feeding strategy.


From beta-nitrothiophenes to ring-fused nitrobenzenes: an overall ring-enlargement process via a facile, aromatization-driven, thermal 6pi electrocyclization.
[reaction: see text] In prosecution of previous work on the thermal cyclization of 1-aryl-4-methanesulfonyl-2-nitro-3-phenylsulfonyl-1,3-butadienes (7), the 3-unsubstituted derivatives 8, deriving from the initial ring opening of 3-nitrothiophene (2), have been likewise found herein to undergo cyclization, followed by aromatization, in analogous mild experimental conditions, leading to the ring-fused homo- or heteroaromatic nitro derivatives 10. The concerted electrocyclic nature of the process is strongly supported by the outcome of tests based on the variation of the polarity of the solvent or of the electron density on the aryl of 8. Thus, the successful application of the process to the non-phenylsulfonyl-activated 8 significantly widens the scope of a synthetically valuable overall ring-opening/ring-closing procedure from nitrothiophenes. Support to the recently renewed interest in thermal 6pi electrocyclizations as a tool for the construction of the benzene ring is furthermore provided.


Indirect immunofluorescent test on spore sampling preparations: a technique for diagnosis of individual mold allergies.
To calculate their respective exposure to mold spores, volumetric spore sampling was performed with Burkard personal air samplers in the homes of six asthmatic patients with different mold allergies, of three patients with baker's asthma and of four healthy controls. The spore samples were investigated with an indirect immunofluorescent test. Spore-specific IgE was detected in the serum of all the asthmatic patients with mold allergies, even in patients with only slightly increased or no detectable specific IgE in Phadezym-RAST. In serum of patients with baker's asthma and healthy controls, no spore-specific IgE was found.


24-hour combination chemotherapy without cisplatin in patients with recurrent or metastatic head and neck cancer.
Sixty-three patients with advanced histologically proven squamous cell carcinomas of the head and neck, considered untreatable other than by chemotherapy, received a combination of vincristine, bleomycin, methotrexate, 5-fluorouracil, and hydrocortisone administered over 24 hours, followed by a folinic acid rescue, every 3 weeks. Fifty-seven patients had received prior radiotherapy and 78% of recurrences were within the radiation field. Sixty-one patients were assessable for response to chemotherapy and 25 (41%) achieved objective responses. Side effects from 167 courses of chemotherapy were minimal and were present only in 38% of patients. There were no cases of bone marrow depression and no drug-induced deaths. Patient compliance was 98%. Chemotherapy responders had a longer median duration of survival of 11.9 months (with four patients still alive at 10, 22, 30, and 90 months) compared with 4.96 months for nonresponders (with two patients alive at 7 and 15 months), p less than 0.001. Ten of 24 chemotherapy responders went on to surgery and eight achieved a complete remission (CR), while only 6/36 nonresponders underwent salvage surgery and all became disease-free. Patients achieving a complete remission had improved survival (median 24.5 months). The presence of metastatic disease was a poor prognostic sign; only 8/30 (27%) responded to chemotherapy and none subsequently achieved complete remission. This safe drug protocol appears to benefit only a small subset of patients, namely those who respond to chemotherapy rendering their tumors operable, but is of no general value in this group of previously irradiated patients since 92% of all patients treated were dead at 2 years.


Cox1 mutation abrogates need for Cox23 in cytochrome c oxidase biogenesis.
Cox23 is a known conserved assembly factor for cytochrome c oxidase, although its role in cytochrome c oxidase (CcO) biogenesis remains unresolved. To gain additional insights into its role, we isolated spontaneous suppressors of the respiratory growth defect in cox23∆ yeast cells. We recovered independent colonies that propagated on glycerol/lactate medium for cox23∆ cells at 37°C. We mapped these mutations to the mitochondrial genome and specifically to COX1 yielding an I101F substitution. The I101F Cox1 allele is a gain-of-function mutation enabling yeast to respire in the absence of Cox23. CcO subunit steady-state levels were restored with the I101F Cox1 suppressor mutation and oxygen consumption and CcO activity were likewise restored. Cells harboring the mitochondrial genome encoding I101F Cox1 were used to delete genes for other CcO assembly factors to test the specificity of the Cox1 mutation as a suppressor of cox23∆ cells. The Cox1 mutant allele fails to support respiratory growth in yeast lacking Cox17, Cox19, Coa1, Coa2, Cox14 or Shy1, demonstrating its specific suppressor activity for cox23∆ cells.


Automated solid-phase extraction of phenolic acids using layered double hydroxide-alumina-polymer disks.
The application of layered double hydroxide-Al2 O3 -polymer mixed-matrix disks for solid-phase extraction is reported for the first time. Al2 O3 is embedded in a polymer matrix followed by an in situ metal-exchange process to obtain a layered double hydroxide-Al2 O3 -polymer mixed-matrix disk with excellent flow-through properties. The extraction performance of the prepared disks is evaluated as a proof of concept for the automated extraction using sequential injection analysis of organic acids (p-hydroxybenzoic acid, 3,4-dihydroxybenzoic acid, gallic acid) following an anion-exchange mechanism. After the solid-phase extraction, phenolic acids were quantified by reversed-phase high-performance liquid chromatography with diode-array detection using a core-shell silica-C18 stationary phase and isocratic elution (acetonitrile/0.5% acetic acid in pure water, 5:95, v/v). High sensitivity and reproducibility were obtained with limits of detection in the range of 0.12-0.25 μg/L (sample volume, 4 mL), and relative standard deviations between 2.9 and 3.4% (10 μg/L, n = 6). Enrichment factors of 34-39 were obtained. Layered double hydroxide-Al2 O3 -polymer mixed-matrix disks had an average lifetime of 50 extractions. Analyte recoveries ranged from 93 to 96% for grape juice and nonalcoholic beer samples.


Ellipsometry with polarisation analysis at cryogenic temperatures inside a vacuum chamber.
In this paper we describe a new variant of null ellipsometry to determine thicknesses and optical properties of thin films on a substrate at cryogenic temperatures. In the PCSA arrangement of ellipsometry the polarizer and the compensator are placed before the substrate and the analyzer after it. Usually, in the null ellipsometry the polarizer and the analyzer are rotated to find the searched minimum in intensity. In our variant we rotate the polarizer and the compensator instead, both being placed in the incoming beam before the substrate. Therefore the polarisation analysis of the reflected beam can be realized by an analyzer at fixed orientation. We developed this method for investigations of thin cryogenic films inside a vacuum chamber where the analyzer and detector had to be placed inside the cold shield at a temperature of T ≈ 90 K close to the substrate. All other optical components were installed at the incoming beam line outside the vacuum chamber, including all components which need to be rotated during the measurements. Our null ellipsometry variant has been tested with condensed krypton films on a highly oriented pyrolytic graphite substrate (HOPG) at a temperature of T ≈ 25 K. We show that it is possible to determine the indices of refraction of condensed krypton and of the HOPG substrate as well as thickness of krypton films with reasonable accuracy.


Using temperature-sensing reticular boluses to aid in the detection of production diseases in dairy cows.
The objective of this study was to investigate associations between increases in reticular temperature (RT) in dairy cows and the diagnosis of metritis, mastitis, lameness, and pneumonia by dairy personnel. A prospective case-control study was conducted on a 2,175-cow dairy operation in Colorado from May 2010 to April 2011. Each cow received an orally administered temperature sensing reticular bolus after parturition and RT measurements were recorded 3 times per day as lactating cows exited the milking parlor. A cow was identified as having an increased RT when a deviation of 0.8°C above baseline (average of readings of previous 10d) was recorded by the TempTrack software (DVM Systems, LLC, Greeley, CO). During the same study period, dairy personnel without access to RT data recorded health events and classified them according to clinical signs observed. A total of 201 health events (cases) were included in the data analysis. Cows with clinical mastitis and pneumonia had significantly higher odds (6.7 and 7.5 times higher, respectively) of having an increased RT of 0.8°C above their baseline within 4d preceding diagnosis when compared with control cows. Specificity and sensitivity for an increase of 0.8°C above baseline RT within 4d of disease diagnosis was 76.85 and 66.97% for mastitis, and 69.23 and 76.92% for pneumonia, respectively. No significant difference in RT was found for cows diagnosed with lameness or metritis. Results of this study suggest that RT monitoring can be a useful tool in the early detection of mastitis and pneumonia in dairy cows.


Analysing migrations of Atlantic cod Gadus morhua in the north-east Atlantic Ocean: then, now and the future.
The application of data storage tags bears the potential for a quantum leap in the research on fish migrations, because not only first-capture and recapture positions are known, but at least theoretically, the migration path during the period at large can be reconstructed. Position, however, cannot be measured directly but has to be estimated using the available data on light, temperature, pressure and salinity. The reconstructed locations based on advanced estimation techniques have been termed geolocations. Examples are discussed which illustrate the applicability of geolocations in individual path descriptions, separation of reproductively isolated populations, timing and areas of spawning, tidal transport and use of protected areas. The examples are based on archival tag data from the North Sea, the Baltic Sea, the Barents Sea and Faroese and Icelandic Waters. Besides presenting the state-of-the-art geolocations for cod Gadus morhua in the north-east Atlantic Ocean, the major aim of this review is to raise awareness of gaps in knowledge and to identify ideas for new research.


Thyrotoxic neuropathy (Basedow's paraplegia).
Polyneuropathy is a rare but possible manifestation of severe hyperthyroidism. The patient reported here developed a polyneuropathy affecting mostly leg muscles (Basedow's paraplegia) during the course of severe thyrotoxicosis. The polyneuropathy was confirmed with sequential electrophysiological studies of nerves and muscles and by muscle biopsy. The involvement of the proximal leg muscle is also interpreted as a neuropathic or nerve-mediated process rather than a concomitant thyrotoxic myopathy.


Multiple typing of Salmonella typhimurium isolates: an epidemiological study.
An epidemiological study was carried out on sixty-four Salmonella typhimurium strains isolated in Palermo during the period January-July 1987 and identified at the Southern Italy Center of Enterobacteriaceae. These included 5 isolates from a small food-poisoning outbreak, which resulted antibiotic susceptible, not colicinogenic and untypable by the phage-type scheme of Anderson. Plasmid profile analysis was not a reliable method to differentiate them from non epidemic strains. The 5 epidemic isolates, belonging to biotype 25a, were assigned into NT 2 phage-type by an accessory set of phages developed in this laboratory. Such biotype/phage-type association was never detected in the remaining Salmonella typhimurium strains isolated during the first 7 months of 1987. Chromosomal DNA analysis provided additional information on the relationships among Salmonella typhimurium isolates.


[Problems and future directions for early detection of lung cancer].
Mass screening methods for lung cancer consist of X-ray examination in men and women over 40 years of age and X-ray examination plus sputum cytology test confined to high risk groups. Examination methods which seem to be most effective for early detection at present are introduced based on the results of the examinations and treatment provided. If we are to conduct this method extensively in the future there remain many problems unsolved yet: how to systematize the execution, to contact with more examinees, to increase examination capability and effectiveness etc. Our recent directions for the nation-wide mass screening of lung cancer consist of four methods: 1. Utilization of local self-governmental mass screening. 2. Mass screening conducted by general practitioners at local clinics. 3. Active cooperation of general practitioners with local self-government. 4. Public participation in the lung project. We should continue our efforts to solve these problems.


Risk and population attributable fraction of stroke subtypes in Japan.
Associations of major risk factors for stroke with total and each type of stroke as well as subtypes of ischemic stroke and their population attributable fractions had not been examined comprehensively. Participants of the Japan Public Health Center-based prospective (JPHC) Study Cohort II without histories of cardiovascular disease and cancer (n=14,797) were followed from 1993 through 2012. Associations of current smoking, hypertension, diabetes, overweight (body mass index ≥ 25 kg/m2), non-high-density lipoprotein cholesterol (non-HDLC) categories, low HDLC (< 40 mg/dL), urine protein, and history of arrhythmia were examined in a mutually-adjusted Cox regression model that included age and sex. Population attributable fraction (PAF) was estimated using the hazard ratios and the prevalence of risk factors among cases. Subjects with hypertension were 1.63 to 1.84 times more likely to develop any type of stroke. Diabetes, low HDLC, current smoking, overweight, urine protein, and arrhythmia were associated with risk of overall and ischemic stroke. Hypertension and urine protein were associated with risk of intracerebral hemorrhage while current smoking, hypertension, and low non-HDLC were associated with subarachnoid hemorrhage. Hypertension alone accounted for more than a quarter of stroke incidence, followed by current smoking and diabetes. High non-HDLC, current smoking, low HDLC, and overweight contributed mostly to large-artery occlusive stroke. Arrhythmia explained 13.2% of embolic stroke. Combined PAFs of all the modifiable risk factors for total, ischemic and large-artery occlusive strokes were 36.7 and 44.5% and 61.5%, respectively. Although there are differences according to the subtypes, hypertension could be regarded as the most crucial target for preventing strokes in Japan.


Social Discounting under Risk.
As a measure of how prosocial behavior depends on social distance, social discounting is defined as the decrease in generosity between the decision maker and the recipient as the social distance increases. While risk is a ubiquitous part of modern life, there is limited research on the relationship between risk and prosocial behavior. In the present experiment, we empirically test whether risk has an influence on social discounting. We use the choice titration procedure to examine this effect. Our data show that independent of risk, participants are less eager to forego money and exhibit more selfishness toward a specific person when the social distance increases; these findings are reflected in the hyperbolic model. Interestingly, risk influences the shape of the social discounting function, which is reflected in the notable different discount rates. Individuals who make decisions under risk yield a smaller discount rate than those who make decisions without risk, i.e., under risk subjects reduce less their generosity as a function of the social distance. Furthermore, this distinct type of generosity occurs typically among individuals with 10-distance recipients but not with the closest- and furthest-social-distance recipients.


Isolation and characterization of an endo-(1,4)-{beta}-glucanase secreted by Achlya ambisexualis.
Models of wall loosening in fungi and other walled eukaryotes require the action of proteins able to reduce the degree of linkage between components of the wall. In the oomycete Achlya ambisexualis, such a role has been proposed for a suite of endoglucanases that are secreted during branching and during the measurable wall softening associated with osmotic stress. We report here the isolation and characterization of one of these isoenzymes. The enzyme has a molecular weight of 32 kDa, a pH optimum of 6.75, a pI of 4.5, and a temperature optimum of 35 C. It is partially inhibited by sulfhydryl-binding reagents and completely inhibited by the tryptophan-binding reagent NBS. The enzyme has an endohydrolytic mode of action with substrate specificity towards glucans that contain β-(1,4) linkages, either alone (carboxymethyl cellulose) or as mixed linkage (1,4-1,3)-β-glucans (e.g., Avena glucan). It does not, however, degrade amorphous insoluble (phosphoric acid swollen) cellulose. Most significantly, the enzyme can also hydrolyze linkages in an Achlya cell wall fraction previously shown to consist of a mixed-linkage (1,4-1,3)-β-glucan. This property is consistent with the long-standing hypothesis that the branching-related endoglucanases of oomycetes play a role in cell wall loosening.


Tacrolimus is an alternative therapy option for the treatment of adult steroid-resistant nephrotic syndrome: a prospective, multicenter clinical trial.
The optimal therapy for adult steroid-resistant nephrotic syndrome (SRNS) remains a therapeutic challenge. We investigated the efficacy and safety of tacrolimus as a promising regimen in Chinese adult patients. A prospective, multicenter trial was conducted in 9 nephrology centers from 2006 to 2008, in patients with SRNS (defined as failure to respond to 1 mg/kg/day of prednisone for 8, and 16 weeks, in focal segmental glomerulosclerosis). Patients were treated with tacrolimus (TAC) plus prednisone for 12 months. TAC dose was titrated to achieve a target trough blood concentration of 5-10 ng/ml for the first 6 months and 4-6 ng/ml for the subsequent 6 months. The primary outcomes included complete or partial remission [complete remission (CR): proteinuria <0.3 g/24 h, with serum albumin ≥ 3.5 g/dl and stable renal function; partial remission (PR): proteinuria between 0.3 and 3.5 g/24 h and a decrease of at least 50 % from the baseline level, with serum albumin ≥ 3.0 g/dl and stable renal function]. Secondary end-points included relapse rate, changes of clinical parameters (proteinuria, serum albumin, and lipid profile) and adverse events. Twenty-four patients with SRNS were enrolled. After 6 months of therapy, CR was achieved in 58.3 % of patients and PR in 16.7 %, yielding a final response rate of 75.0 %. The decrease in proteinuria was 43.1 ± 17.5 % after the first month of treatment (P < 0.001). Complete or PR was achieved in 6 of 8 patients with minimal change disease, 4 of 6 patients with mesangioproliferative glomerulonephritis (MsPGN), 6 of 7 patients with focal segmental glomerulosclerosis (FSGS), and all 2 patients with IgA nephropathy. Two patients (1 with MsPGN and 1 with FSGS) experienced relapses during the subsequent 6 months of follow-up. Adverse events included infection, hand tremor, diarrhea, acute reversible or persistent nephrotoxicity. In conjunction with prednisone, TAC may be an alternative therapeutic regimen for adult SRNS patients. However, adverse events in these patients should be carefully monitored, especially at the beginning of treatment. Randomized controlled trials with longer follow-up are warranted.


Handling postpartum haemorrhage- obstetrics between tradition and modernity in post-war Sierra Leone.
How traditional birth attendants (TBAs) in post-war Sierra Leone explain, handle and prevent postpartum haemorrhage (PPH) and their potential role in a better management of PPH to reduce maternal mortality in this low resource setting. Semi-quantitative interviews about knowledge and measures in PPH and participant observation with 140 Sierra Leonean birth attendants, divided in three groups: (A) TBAs who never attended any official training course (n = 82); (B) TBAs who attended at least one official training course (n = 48); and (C) officially trained birth attendants (n = 10). There are several observable gaps in the knowledge of TBAs about PPH compared to modern obstetrics, however similar procedures exist. Herbal medicine is applied; metaphysical convictions about PPH remain present. Training courses show an impact. Officially trained birth attendants demonstrate knowledge deficiencies and lack resources and infrastructure to manage PPH adequately. Morbidity and mortality of PPH in Sierra Leone is related to several factors and not solely to the ignorance of TBAs. TBAs still play an important role for many women there. Hence improvement of the formal health sector should be combined with life-saving programmes integrating TBAs in the care for the pregnant, delivering and breastfeeding mothers.


Reinforced cementoplasty for pelvic tumour lesions and pelvic traumatic fractures: preliminary experience.
Pelvic bone pathological lesions and traumatic fractures are a considerable source of pain and disability. In this study, we sought to evaluate the effectiveness of reinforced cementoplasty (RC) in painful and unstable lesions involving the pelvic bone in terms of pain relief and functional recovery. All patients with neoplastic lesion or pelvic fracture for whom a pelvic bone RC was carried out between November 2013 and October 2017 were included in our study. All patients who failed the medical management, patients unsuitable for surgery, and patients with unstable osteolytic lesions were eligible to RC. Clinical outcome was evaluated with a 1-month and 6-month post-procedure follow-up. The primary endpoint was local pain relief measured by the visual analogue scale (VAS). Twenty-two patients (18 females, 4 males; mean age of 65.4 ± 13.3 years [range 38-80]) presenting with painful and unstable pelvic lesions were treated by RC during the study period. Among the 22 patients, 8 patients presented with unstable pelvic fractures (3 patients with iliac crest fracture, 3 with sacral fractures, and the remaining 2 with peri-acetabular fractures). No procedure-related complications were recorded. All patients had significant pain relief and functional improvement at 1 month. One patient (4.5%) had suffered a secondary fracture due to local tumour progression. Reinforced cementoplasty is an original minimally invasive technique that may help in providing pain relief and effective bone stability for neoplastic and traumatic lesions involving the pelvic bone. • Reinforced cementoplasty is feasible in both traumatic fractures and tumoural bone lesions of the pelvis. • Reinforced cementoplasty for pelvic bone lesions provides pain relief and functional recovery. • Recurrence of pelvic bone fracture was observed in 4.5% of the cases in our series.


Arsenic, Lead, and Cadmium in U.S. Mushrooms and Substrate in Relation to Dietary Exposure.
Wild mushrooms can absorb high quantities of metal(loid)s, yet the concentration, speciation, and localization of As, Pb, and Cd in cultivated mushrooms, particularly in the United States, are unresolved. We collected 40 samples of 12 types of raw mushrooms from 2 geographic locations that produce the majority of marketable U.S. mushrooms and analyzed the total As, Pb, and Cd content, the speciation and localization of As in select samples, and assessed the metal sources and substrate-to-fruit transfer at one representative farm. Cremini mushrooms contained significantly higher total As concentrations than Shiitake and localized the As differently; while As in Cremini was distributed throughout the fruiting body, it was localized to the hymenophore region in Shiitake. Cd was significantly higher in Royal Trumpet than in White Button, Cremini, and Portobello, while no difference was observed in Pb levels among the mushrooms. Concentrations of As, Pb, and Cd were less than 1 μg g(-1) d.w. in all mushroom samples, and the overall risk of As, Cd, and Pb intake from mushroom consumption is low in the U.S. However, higher percentages of tolerable intake levels are observed when calculating risk based on single serving-sizes or when substrate contains elevated levels of metal(loid)s.


NK cells and their ability to modulate T cells during virus infections.
Natural killer (NK) cells are important in protection against virus infections, and many viruses have evolved mechanisms to thwart NK cell activity. NK cells respond to inflammatory signals at an early stage of virus infection, resulting in proliferation, cytokine production, and cytolytic activity that can reduce virus loads. Moreover, the rapid kinetics of the NK cell response enables NK cells to influence other populations of innate immune cells, affect the inflammatory milieu, and guide adaptive immune responses to infection. Early NK cell interactions with other leukocytes can have long-lasting effects on the number and quality of memory T cells, as well as impact the exhaustion of T cells during chronic infections. The ability of NK cells to modulate T cell responses can be mediated through direct T-NK interactions, cytokine production, or indirectly through dendritic cells and other cell types. Herein, we summarize our current understanding of how NK cells interact with T cells, dendritic cells, B cells, and other cell types involved in adaptive immune responses to virus infection. We outline several mechanisms by which NK cells enhance or suppress adaptive immune response and long-lived immunological memory.


Revision Breast Augmentation at the Time of Cardiac Sarcoma Resection: The Importance of Pocket Control When Inframammary Approach Is Combined with Simultaneous Sternotomy.
Sternotomy in patients with previous breast augmentation becomes an aesthetic challenge when an inframammary approach is utilized over the traditional midline skin incision. Although the inframammary fold approach offers a well-concealed scar when compared with the midline chest incision, patients with a history of previous breast augmentation are at risk for alteration of the anatomy leading to symmastia, implant malposition, and asymmetry. We present a case report of sternotomy and resection of a mediastinal perivascular epithelioid cell tumor with concomitant revision augmentation with silicone implants and SERI Scaffold. Our patient had an uncomplicated postoperative course and a good cosmetic result 1 year after concomitant revision augmentation in conjunction with cardiac tumor resection. In conclusion, the authors feel that despite the difficulties in performing breast augmentation in patients undergoing thoracic surgery, it is possible to obtain good results. It is necessary to reinforce the repair with a mesh to recreate support and proper anatomy.


The State of Health in Older Adults in Japan: Trends in Disability, Chronic Medical Conditions and Mortality.
Both life expectancy and healthy life expectancy in Japan have been increasing and are among the highest in the world, but the gap between them has also been widening. To examine the recent trends in old age disability, chronic medical conditions and mortality in Japan, we retrospectively analyzed three nationally representative datasets: Comprehensive Survey of Living Conditions (2001-2013), Patient Survey (1996-2011) and Vital Statistics (1995-2010). We obtained the sex- and age-stratified trends in disability rate, treatment rates of nine selected chronic medical conditions (cerebrovascular diseases, joint disorders, fractures, osteoporosis, ischemic heart disease, diabetes mellitus, hypertension, pneumonia and malignant neoplasms), total mortality rate and mortality rates from specific causes (cerebrovascular diseases, heart diseases, pneumonia and malignant neoplasms) in both sexes in four age strata (65-69, 70-74, 75-79, 80-84 years). Disability rates declined significantly in both sexes. Treatment rates of all selected medical conditions also decreased significantly, except for fractures in women and pneumonia. Both total mortality rate and cause-specific mortality rates decreased in both sexes. We concluded that the recent decline in disability rates, treatment rates of chronic medical conditions and mortality rates points toward overall improvement in health conditions in adults over the age of 65 years in Japan. Nonetheless, considering the increase in the number of older adults, the absolute number of older adults with disability or chronic medical conditions will continue to increase and challenge medical and long-term care systems.


[Characteristics of work-loss in diseases of the peripheral nervous system].
Diseases of the peripheral nervous system (PNS) rank fourth among all causes of temporal loss of working ability and first in the structure of neurological morbidity causing temporal disability. Statistical service based on the principles of the International Classification of Diseases, Injuries and Causes of Death does not provide the neurologic service with data about loss of the working time due to PNS diseases. In the comprehensive work on the improvement of neurologic care of patients with PNS diseases conducted in Byelorussia an important place has been recently given to the systematic monitoring of the temporal disability rate which decreased by 28.3% over a period of 3 years (1983-1985).


The Importance of Neurological Examination for the Indication of Computed Tomography of the Brain in Pediatric Emergency Room.
In this study, records of the children who underwent Computed Tomography of the Brain (CTB) were reviewed to increase the awareness of pediatricians to protect patients from radiation, whether CTB was used with right indications or if it was determinative for diagnosis. In total, in this study, 342 cases applied to our Pediatric Emergency Polyclinic between January 2005-December 2010 were retrospectively evaluated regarding complaints at admission, neurological examination and CTB results. The sensitivity and specificity of the neurological examination in detecting the CTB pathology was determined. The results were normal in 319 of the 342 cases with CBT and abnormal in 23, out of which abnormal CTB results were only in three (0.99%) of the 301 patients with normal neurological examination results and in 20 (48.8%) of 41 patients with abnormal neurological examination results. The difference between the two groups was statistically significant (p=0.001). The sensitivity and specificity of the neurological examination in detecting CTB pathology were 87% and 94%, respectively. Detailed neurological examination of the patients in the pediatric emergency department has a key role in determining the indications for CTB. Clinical follow-up should guide neuroradiological imaging in children with normal results of the neurological examination.


Anatomy-guided domain adaptation for 3D in-bed human pose estimation.
3D human pose estimation is a key component of clinical monitoring systems. The clinical applicability of deep pose estimation models, however, is limited by their poor generalization under domain shifts along with their need for sufficient labeled training data. As a remedy, we present a novel domain adaptation method, adapting a model from a labeled source to a shifted unlabeled target domain. Our method comprises two complementary adaptation strategies based on prior knowledge about human anatomy. First, we guide the learning process in the target domain by constraining predictions to the space of anatomically plausible poses. To this end, we embed the prior knowledge into an anatomical loss function that penalizes asymmetric limb lengths, implausible bone lengths, and implausible joint angles. Second, we propose to filter pseudo labels for self-training according to their anatomical plausibility and incorporate the concept into the Mean Teacher paradigm. We unify both strategies in a point cloud-based framework applicable to unsupervised and source-free domain adaptation. Evaluation is performed for in-bed pose estimation under two adaptation scenarios, using the public SLP dataset and a newly created dataset. Our method consistently outperforms various state-of-the-art domain adaptation methods, surpasses the baseline model by 31%/66%, and reduces the domain gap by 65%/82%. Source code is available at https://github.com/multimodallearning/da-3dhpe-anatomy.


Electrochemical Skin Conductance May Be Used to Screen for Diabetic Cardiac Autonomic Neuropathy in a Chinese Population with Diabetes.
Aims. This study aimed to assess whether the electrochemical skin conductance (ESC) could be used to screen for diabetic cardiac autonomic neuropathy (DCAN) in a Chinese population with diabetes. Methods. We recruited 75 patients with type 2 diabetes mellitus (T2DM) and 45 controls without diabetes. DCAN was diagnosed by the cardiovascular autonomic reflex tests (CARTs) as gold standard. In all subjects ESCs of hands and feet were also detected by SUDOSCAN™ as a new screening method. The efficacy was assessed by receiver operating characteristic (ROC) curve analysis. Results. The ESCs of both hands and feet were significantly lower in T2DM patients with DCAN than those without DCAN (67.33 ± 15.37 versus 78.03 ± 13.73, P = 0.002, and 57.77 ± 20.99 versus 75.03 ± 11.41, P < 0.001). The ROC curve analysis showed the areas under the ROC curve were both 0.75 for ESCs of hands and feet in screening DCAN. And the optimal cut-off values of ESCs, sensitivities, and specificities were 76 μS, 76.7%, and 75.6% for hands and 75 μS, 80.0%, and 60.0% for feet, respectively. Conclusions. ESC measurement is a reliable and feasible method to screen DCAN in the Chinese population with diabetes before further diagnosis with CARTs.


Bisphosphonate-associated osteonecrosis of the jaw. A proposal for conservative treatment.
The use of bisphosphonates (BPs) has proven effective in the treatment of bone-related diseases, despite the potential risk of developing osteonecrosis of the jaw (ONJ). So far, results for the treatment of ONJ have not been satisfactory. In our study, we have treated two patients diagnosed with ONJ. In addition to local treatments a hydrogel was applied, with promising results. The fistulae disappeared 2-3 weeks into the treatment. After a six-month follow-up period there has been no sign of recurrence. The extent of maxillary bone exposure has diminished notably, although not entirely disappeared. In all cases, the patients exhibit no other symptoms (they suffer from no pain or swelling or functional impotence). For this reason we believe this protocol might be useful in the case of patients who suffer from pain and fistulation secondary to BP-associated ONJ to improve the state of their lesions until definitive treatment can be undertaken. Although these findings are not conclusive, given that we are reporting data on two patients only, we believe that this might be an alternative treatment in refractory cases where other therapies are counter-indicated. A controlled randomized and prospective study would be required to confirm our findings.


Leukocyte Nucleolus and Anisakis pegreffii-When Falling Apart Means Falling in Place.
The view of the nucleolus as a mere ribosomal factory has been recently expanded, highlighting its essential role in immune and stress-related signalling and orchestrating. It has been shown that the nucleolus structure, formed around nucleolus organiser regions (NORs) and attributed Cajal bodies, is prone to disassembly and reassembly correlated to various physiological and pathological stimuli. To evaluate the effect of parasite stimulus on the structure of the leukocyte nucleolus, we exposed rat peripheral blood mononuclear cells (PBMC) to the crude extract of the nematode A. pegreffii (Anisakidae), and compared the observed changes to the effect of control (RPMI-1640 media), immunosuppressive (MPA) and immunostimulant treatment (bacterial lipopolysaccharide (LPS) and viral analogue polyinosinic:polycytidylic acid (poly I:C)) by confocal microscopy. Poly I:C triggered the most accentuated changes such as nucleolar fragmentation and structural unravelling, LPS induced nucleolus thickening reminiscent of cell activation, while MPA induced disassembly of dense fibrillar and granular components. A. pegreffii crude extract triggered nucleolar segregation, expectedly more enhanced in treatment with a higher dose. This is the first evidence that leukocyte nucleoli already undergo structural changes 12 h post-parasitic stimuli, although these are likely to subside after successful cell activation.


Acute kidney injury in sepsis.
Acute kidney injury (AKI) and sepsis carry consensus definitions. The simultaneous presence of both identifies septic AKI. Septic AKI is the most common AKI syndrome in ICU and accounts for approximately half of all such AKI. Its pathophysiology remains poorly understood, but animal models and lack of histological changes suggest that, at least initially, septic AKI may be a functional phenomenon with combined microvascular shunting and tubular cell stress. The diagnosis remains based on clinical assessment and measurement of urinary output and serum creatinine. However, multiple biomarkers and especially cell cycle arrest biomarkers are gaining acceptance. Prevention of septic AKI remains based on the treatment of sepsis and on early resuscitation. Such resuscitation relies on the judicious use of both fluids and vasoactive drugs. In particular, there is strong evidence that starch-containing fluids are nephrotoxic and decrease renal function and suggestive evidence that chloride-rich fluid may also adversely affect renal function. Vasoactive drugs have variable effects on renal function in septic AKI. At this time, norepinephrine is the dominant agent, but vasopressin may also have a role. Despite supportive therapies, renal function may be temporarily or completely lost. In such patients, renal replacement therapy (RRT) becomes necessary. The optimal intensity of this therapy has been established, while the timing of when to commence RRT is now a focus of investigation. If sepsis resolves, the majority of patients recover renal function. Yet, even a single episode of septic AKI is associated with increased subsequent risk of chronic kidney disease.


Prognostic enrichment design in clinical trials for autosomal dominant polycystic kidney disease: the HALT-PKD clinical trial.
Patients with mild autosomal dominant polycystic kidney disease (ADPKD) are less likely to be informative in randomized clinical trials (RCTs). We previously developed an imaging classification of ADPKD (typical diffuse cyst distribution Class 1A-E and atypical cyst distribution Class 2) for prognostic enrichment design in RCTs. We investigated whether using this classification would have increased the power to detect a beneficial treatment effect of rigorous blood pressure (BP) control on HALT-PKD participants with early disease (Study A). Post hoc analysis of the early disease HALT-PKD study, an RCT that studied the effect of rigorous versus standard BP control on rates of total kidney volume (TKV) increase and estimated glomerular filtration rate (eGFR) decline in ADPKD patients with eGFR >60 mL/min/1.73 m2. Five hundred and fifty-one patients were classified by two observers (98.2% agreement) into Class 1A (6.2%), 1B (20.3%), 1C (34.1%), 1D (22.1%), 1E (11.8%) and 2 (5.4%). The TKV increase and eGFR decline became steeper from Class 1A through 1E. Rigorous BP control had been shown to be associated with slower TKV increase, without a significant overall effect on the rate of eGFR decline (faster in the first 4 months and marginally slower thereafter). Merging Classes 1A and 2 (lowest severity), 1B and 1C (intermediate severity) and 1D and 1E (highest severity) detected stronger beneficial effects on TKV increase and eGFR decline in Class 1D and E with a smaller number of patients. Strategies for prognostic enrichment, such as image classification, should be used in the design of RCTs for ADPKD to increase their power and reduce their cost.


Ceramide induces mitochondrial activation and apoptosis via a Bax-dependent pathway in human carcinoma cells.
The intracellular pathways leading to mitochondrial activation and subsequent cell death in the ceramide-mediated stress response have been intensively studied in recent years. Experimental evidence has been provided that ceramide-induced apoptosis is inhibited by overexpression of antiapoptotic proteins of the Bcl-2 family. However, the direct effect of proapoptotic gene products, e.g. Bax, on ceramide-induced death signalling has not yet been studied in detail. In the present work, we show by measurement of mitochondrial permeability transition, cytochrome c release, activation of caspase-3 and DNA fragmentation that ceramide-induced apoptosis is marginal in Bax-negative DU 145 cells. Reconstitution of Bax by generation of DU 145 cells stably expressing this proapoptotic factor, clearly enhanced ceramide-induced apoptosis at all levels of the mitochondrial signalling cascade. Using the broad-range caspase inhibitor zVAD-fmk and zDEVD-fmk, an inhibitor of caspase-3-like activities, we demonstrate that the ceramide-induced mitochondrial activation in Bax-transfected DU 145 cells is caspase-independent. On the other hand, apoptotic events located downstream of the mitochondria, e.g. DNA fragmentation, were shown to be caspase-dependent. This influence of Bax on ceramide-induced apoptosis was confirmed in another cellular system: whereas Bax-positive HCT116 wild type cells were very sensitive towards induction of cell death by C(2)-ceramide, sensitivity of Bax knock-out HCT116 cells was significantly reduced. Thus, we conclude that Bax is a key activator of ceramide-mediated death pathways.


Nothramicin, a new anthracycline antibiotic from Nocardia sp. MJ896-43F17.
A new antibiotic designated nothramicin was isolated from the culture broth of Nocardia sp. MJ896-43F17 which was closely related to Nocardia brasiliensis. It was isolated by the Diaion HP-20 column chromatography, butyl acetate extraction and purified by HPLC. It inhibited the growth of mycobacteria at the concentration of 1.56 approximately 25 microg/ml. Nothramicin was revealed to be a new member of anthracycline antibiotics by the various spectroscopies.