Glutamine and interleukin-1beta interact at the level of Sp1 and nuclear factor-kappaB to regulate argininosuccinate synthetase gene expression.
We previously demonstrated that the expression of the argininosuccinate synthetase (ASS) gene, a key step in nitric oxide production, is stimulated either by interleukin-1beta[Brasse-Lagnel et al. (2005) Biochimie 87, 403-9] or by glutamine in Caco-2 cells [Brasse-Lagnel et al. (2003) J. Biol. Chem. 278, 52504-10], through the activation of transcription factors nuclear factor-kappaB and Sp1, respectively. In these cells, the fact that glutamine stimulated the expression of a gene induced by pro-inflammatory factors appeared paradoxical as the amino acid is known to exert anti-inflammatory properties in intestinal cells. We therefore investigated the effect of simultaneous addition of both glutamine and interleukin-1beta on ASS gene expression in Caco-2 cells. In the presence of both compounds for 4 h, the increases in ASS activity, protein amount and mRNA level were almost totally inhibited, implying a reciprocal inhibition between the amino acid and the cytokine. The inhibition was exerted at the level of the transcription factors Sp1 and nuclear-kappaB: (a) interleukin-1beta inhibited the glutamine-stimulated DNA-binding of Sp1, which might be related to a decrease of its glutamine-induced O-glycosylation, and (b) glutamine induced per se a decrease in the amount of nuclear p65 protein without affecting the stimulating effect of interleukin-1beta on nuclear factor-kappaB, which might be related to the metabolism of glutamine into glutamate. The present results constitute the first demonstration of a reciprocal inhibition between the effects of an amino acid and a cytokine on gene expression, and provide a molecular basis for the protective role of glutamine against inflammation in the intestine.


Behavioral flexibility in an invasive bird is independent of other behaviors.
Behavioral flexibility is considered important for a species to adapt to environmental change. However, it is unclear how behavioral flexibility works: it relates to problem solving ability and speed in unpredictable ways, which leaves an open question of whether behavioral flexibility varies with differences in other behaviors. If present, such correlations would mask which behavior causes individuals to vary. I investigated whether behavioral flexibility (reversal learning) performances were linked with other behaviors in great-tailed grackles, an invasive bird. I found that behavioral flexibility did not significantly correlate with neophobia, exploration, risk aversion, persistence, or motor diversity. This suggests that great-tailed grackle performance in behavioral flexibility tasks reflects a distinct source of individual variation. Maintaining multiple distinct sources of individual variation, and particularly variation in behavioral flexibility, may be a mechanism for coping with the diversity of novel elements in their environments and facilitate this species' invasion success.


Psychosocial work environment among employed Swedish dairy and pig farmworkers.
The purpose of this study was to investigate the psychosocial work environment for employed dairy and pig farmworkers in southern Sweden and to identify potential risk factors related to the psychosocial work environment for the development of musculoskeletal disorders (MSDs). Thirty-seven workers on 10 dairy farms and 30 workers on 10 pig farms participated in the study. The study was based on a Swedish translation of the short version of the Copenhagen Psychosocial Questionnaire (COPSOQ) for analyses of self-perceived psychosocial work environment and the general Nordic questionnaire for analyses of self-perceived MSDs. In general, the psychosocial work environment was assessed as "good" by both the dairy and pig farmworkers. However, the dairy and pig farmworkers experienced lower work demands, poorer general and mental health, and poorer vitality (physical and mental strength, vigor, and energy) compared to other occupations. Furthermore, the results indicated that the quality of leadership, feedback, and social support at work were poorer at the dairy farms than at the pig farms. No significant risk factors related to the psychosocial work environment were identified for MSDs in "the back" and in the "upper extremities." This study indicates that the psychosocial work environment for the dairy and pig farmworkers may well be improved in order to promote these workplaces as attractive and healthful. This especially seems to be the case concerning the quality of leadership, feedback, and social support at work for the dairy farmworkers. Furthermore, the present study suggests the probability that physical factors are more likely to lead to MSDs among employed livestock workers than factors related to the psychosocial work environment.


Problems and Pitfalls in the Analysis of Amygdalin and Its Epimer.
α-[(6-O-β-d-Glucopyranosyl-β-d-glucopyranosyl)oxy]-(αR)-benzeneacetonitrile, or R-amygdalin, is the most common cyanogenic glycoside found in seeds and kernels of the Rosaceae family and other plant genera such as Passiflora. Many commercially important seeds are analyzed for amygdalin content. In "alternative medicine", amygdalin has been sold as a treatment for cancer for several decades without any rigorous scientific support for its efficacy. We have found that there are some inconsistencies and possible problems in the published analytical chemistry of amygdalin. It is shown that some analytical approaches do not account for the presence of the S-isomer; therefore, a fast reliable method was developed using a chiral stationary phase and HPLC. This approach allows "real-time" monitoring and complete and highly efficient separations. It is found that the S-amygdalin continuously forms in aqueous solutions. A striking result is that the conversion of amygdalin is glassware dependent. "Clean" vials from various vendors can show drastically different reaction rates of the conversion to the isomer (S-amygdalin, also called neo-amygdalin). The epimerization kinetics are dependent on the solvent, temperature, pH, and the nature of the container. For example, epimerization in water was complete in <15 min in a new glass vial taken from the box, whereas it can take >1 h in specially cleaned glassware. Conversely, epimerization can be significantly delayed at high temperature if high-density polyethylene is used as the container. Hence, inert plastic containers are recommended for storage of aqueous amygdalin solutions. Commercial preparations of R-amygdalin actually contain greater quantities of S-amygdalin and ∼ 5% of other degradation products.


Bathymetric diffraction of basin-scale hydroacoustic signals.
The ocean is nearly transparent to low frequency sound permitting the observation of distant events such as earthquakes or explosions at fully basin scales. For very low frequency the ocean acts as a shallow-water waveguide and lateral variability in bathymetry can lead to out-of-plane effects. In this paper, data from the International Monitoring System of the Comprehensive Test Ban Treaty Organization (CTBTO) is used to present two cases where robustly localized seismic events in locations clearly within the two-dimensional (2-D) shadow of a continent or large island generate T-phase signals that are received on a hydro-acoustic station. A fully three- dimensional parabolic equation model is used to demonstrate that lateral variability of the bathymetry can lead to diffraction, explaining both observations. The implications of this are that the CTBTO network has greater coverage than predicted by 2-D models and that inclusion of diffraction in future processing can improve the automatic global association of hydroacoustic events.


Enzyme immunoassay for cuprozinc-superoxide dismutase in serum and urine.
A highly sensitive enzyme immunoassay system for the determination of cuprozinc-superoxide dismutase (Cu,Zn-SOD) in serum and urine by using beta-galactosidase as a labeling enzyme is reported. This assay had a greater sensitivity than that of previously reported radioimmunoassay methods and could measure from 0.05 to 10.0 ng of Cu,Zn-SOD with good reproducibility. Coefficients of variation for this enzyme immunoassay were 2.8-8.3% within a day and 5.6-16.1% between days. The average recoveries were 96-103% from sera and 96-105% from urines, respectively. Using this enzyme immunoassay, serum Cu,Zn-SOD concentrations increased significantly in patients with renal diseases and were slightly elevated in patients with liver diseases. Urinary Cu,Zn-SOD appeared to be the highest in all renal diseases. By immunofluorescent staining, Cu,Zn-SOD was located in the thickened portions of the glomerular basement membrane and proliferating mesangial cells of the kidney tissue from a patient with membranous glomerulonephritis.


Assessment of tools for marker-assisted selection in a marine commercial species: significant association between MSTN-1 gene polymorphism and growth traits.
Growth is a priority trait from the point of view of genetic improvement. Molecular markers linked to quantitative trait loci (QTL) have been regarded as useful for marker-assisted selection in complex traits as growth. Polymorphisms have been studied in five candidate genes influencing growth in gilthead seabream (Sparus aurata): the growth hormone (GH), insulin-like growth factor-1 (IGF-1), myostatin (MSTN-1), prolactin (PRL), and somatolactin (SL) genes. Specimens evaluated were from a commercial broodstock comprising 131 breeders (from which 36 males and 44 females contributed to the progeny). In all samples eleven gene fragments, covering more than 13,000 bp, generated by PCR-RFLP, were analyzed; tests were made for significant associations between these markers and growth traits. ANOVA results showed a significant association between MSTN-1 gene polymorphism and growth traits. Pairwise tests revealed several RFLPs in the MSTN-1 gene with significant heterogeneity of genotypes among size groups. PRL and MSTN-1 genes presented linkage disequilibrium. The MSTN-1 gene was mapped in the centromeric region of a medium-size acrocentric chromosome pair.


Molecular beacon anchored onto a graphene oxide substrate.
In this article, we report a graphene oxide-based nanosensor incorporating semiconductor quantum dots linked to DNA-aptamers that functions as a 'turn-off' fluorescent nanosensor for detection of low concentrations of analytes. A specific demonstration of this turn-off aptasensor is presented for the case of the detection of mercury (II) ions. In this system, ensembles of aptamer-based quantum-dot sensors are anchored onto graphene oxide (GO) flakes which provide a platform for analyte detection in the vicinity of GO. Herein, the operation of this ensemble-based nanosensor is demonstrated for mercury ions, which upon addition of mercury, quenching of the emission intensity from the quantum dots is observed due to resonance energy transfer between quantum dots and the gold nanoparticle connected via a mercury target aptamer. A key result is that the usually dominant effect of quenching of the quantum dot due to close proximity to the GO can be reduced to negligible levels by using a linker molecule in conjunctions with the aptamer-based nanosensor. The effect of ionic concentration of the background matrix on the emission intensity was also investigated. The sensor system is found to be highly selective towards mercury and exhibits a linear behavior (r 2 > 0.99) in the nanomolar concentration range. The detection limit of the sensor towards mercury with no GO present was found to be 16.5 nM. With GO attached to molecular beacon via 14 base, 35 base, and 51 base long linker DNA, the detection limit was found to be 38.4 nM, 9.45 nM, and 11.38 nM; respectively.


The Cochlear Baha 4 Attract System - design concepts, surgical technique and early clinical results.
Bone conduction implant systems utilize osseointegrated fixtures to transmit sound through the bones of the skull. They allow patients with hearing loss to receive acoustic signals directly to the inner ear, bypassing the outer and middle ear. The new Cochlear™ Baha(®) Attract System (Cochlear Bone Anchored Solutions AB, Mölnlycke, Sweden) has been designed as a non-skin penetration hearing implant. The system uses magnetic coupling to hold the external sound processor in place and transmit acoustic energy. An implantable magnet is anchored to the skull via a single osseointegrated fixture, maximizing the efficiency of energy sound transfer. The interposed soft tissue is protected by a SoftWear pad that evenly distributes pressure in order to minimize the risk of pressure necrosis. This article summarizes the design features and early clinical results of the Baha 4 Attract System and provides context as to its place in the broader hearing aid market.


The Coming of Age in Iodane-Guided ortho-C-H Propargylation: From Insight to Synthetic Potential.
As early as 1991 Ochiai et al. reported that an acid-activated form of phenyliodine diacetate, PhI(OAc)2 , undergoes a reaction with propargyl-silanes, germanes and stannanes to give the ortho-propargyl iodobenzene. This formal C-H alkylation was proposed to take place through an unusual (even to date) iodonio-based [3,3] rearrangement of an intermediate allenylsilane. Although this mechanistic principle has been invoked in related iodane-directed C-H coupling reaction, some underlying principles have remained unaddressed, and the reaction rarely employed. Herein, DFT evidence for a mechanism best described as iodine-guided electrophilic aromatic substitution is presented. Using a newly optimized reaction protocol that significantly reduces the undesired reduction process, the potency of the method is showcased through the synthesis of >40 structurally diverse ortho-iodo propargyl (or allenyl) arenes.


Microchip technology for automated and parallel patch-clamp recording.
The patch-clamp technique is the state-of-the-art technology for the study of a large class of membrane proteins called ion channels. Ion channels mediate electrical current flow, have crucial roles in cellular physiology, and are important drug targets. However, patch clamping is a laborious process requiring a skilled experimenter and is, therefore, not compatible with the high throughput needed in drug development. The solution for automated and parallel patch-clamp measurements that is provided by microchip technology is presented here.


Comparison of radiation exposure and clinical outcomes between transradial and transfemoral diagnostic cerebral approaches: a retrospective study.
To identify and compare patient and procedural variables that are associated with a high radiation dose exposure and worse clinical outcomes between transradial arterial (TRA) and transfemoral arterial (TFA) approaches. This was a retrospective analysis. A community hospital during the initial phase of adopting a TRA-first approach. A resultant 215 subjects who only underwent diagnostic cerebral angiograms (DCA) after excluding all therapeutic procedures and patients under 18 years. Only DCA from 1 May 2018 to 31 January 2021. We compared radiation exposure parameters (total fluoroscopy time (FT), total radiation dose (TD) and dose area product (DAP), number of vessels injected and Patient-Reported Global Health Physical and Mental Outcome Scores (PROGHS) at 30 days postprocedure between groups. FT was significantly greater in TRA compared with TFA (p<0.001). In addition, TRA had a significantly higher TD (p=0.002) and DAP (p=0.005) when compared with TFA. Analysis of only 6-vessel DCAs also showed that TRA had a significantly higher FT, DAP and TD in comparison to TFA. Despite observing a longer FT in TRA, results showed fewer vessels injected and a notably lower success rate in acquiring a 6-vessel DCA using the TRA. Further analysis of the effect of vessel number on FT using general linear models showed that with every increase of one vessel, the FT increases by 2.2 min for TRA (p<0.001; 95% CI 1.03 to 3.36) and by 1.3 min for TFA (p<0.001; 95% CI 0.72 to 1.83). There was no significant difference between groups in PROGHS mental and physical t-scores at 30 days postprocedure, even though our cohort showed a significantly greater percentage of TRA procedures done in the outpatient setting. Adopting a TRA first approach for DCAs may be initially associated with a higher radiation dose for the patient. Better strategies and devices are needed to mitigate this effect.


Membrane requirements for uridylylation of the poliovirus VPg protein and viral RNA synthesis in vitro.
Efficient translation of poliovirus (PV) RNA in uninfected HeLa cell extracts generates all of the viral proteins required to carry out viral RNA replication and encapsidation and to produce infectious virus in vitro. In infected cells, viral RNA replication occurs in ribonucleoprotein complexes associated with clusters of vesicles that are formed from preexisting intracellular organelles, which serve as a scaffold for the viral RNA replication complex. In this study, we have examined the role of membranes in viral RNA replication in vitro. Electron microscopic and biochemical examination of extracts actively engaged in viral RNA replication failed to reveal a significant increase in vesicular membrane structures or the protective aggregation of vesicles observed in PV-infected cells. Viral, nonstructural replication proteins, however, bind to heterogeneous membrane fragments in the extract. Treatment of the extracts with nonionic detergents, a membrane-altering inhibitor of fatty acid synthesis (cerulenin), or an inhibitor of intracellular membrane trafficking (brefeldin A) prevents the formation of active replication complexes in vitro, under conditions in which polyprotein synthesis and processing occur normally. Under all three of these conditions, synthesis of uridylylated VPg to form the primer for initiation of viral RNA synthesis, as well as subsequent viral RNA replication, was inhibited. Thus, although organized membranous structures morphologically similar to the vesicles observed in infected cells do not appear to form in vitro, intact membranes are required for viral RNA synthesis, including the first step of forming the uridylylated VPg primer for RNA chain elongation.


The Scoring Challenge of Emotional Intelligence Ability Tests: A Confirmatory Factor Analysis Approach to Model Substantive and Method Effects Using Raw Item Scores.
The internal structure of ability emotional intelligence (EI) tests at item level has been hardly studied, and if studied often the predicted structure did not show. In the present study, an a priori model for responses to EI ability items using Likert response scales with a Situational Judgement Test (SJT) format is investigated with confirmatory factor analysis. The model consists of (1) a target EI ability factor, (2) an acquiescence factor, which is a method factor induced by the Likert response scales, and (3) design-based error covariances, which are induced by the SJT format. It is investigated whether this a priori model can account for the observed associations between the raw item responses of the Components of Emotion Understanding Test-24 (CEUT-24). The CEUT-24 is a new test developed to assess emotion understanding, a key aspect of the EI ability construct, based on the componential emotion framework. The sample consisted of 1184 participants (15-22 years old) from four European countries (United Kingdom, Belgium, Germany, and Spain) speaking four different languages (English, Dutch, German and Spanish). Findings showed that the a priori model fitted the data well in all four languages. Furthermore, measurement invariance testing gave evidence for a well-fitting configural, metric, and partial scalar invariance model. The conclusion is that within a regular CFA framework using raw observed items responses, method factors (acquiescence response style and scenario induced variance) can be disentangled from the targeted EI ability factor.


Abrasio axillae in hyperhidrosis.
Forty-one patients with hyperhidrosis axillae were operated on. The subcutaneous curettage in 20 patients was compared with radical excision in 21 patients. Comparison of the results of both operations disclosed no difference in the elimination of the sweat secretion, but the method of curretage is superior, because it can be repeated if necessary and leaves practically no scars.


Kindlin-2 Regulates the Growth of Breast Cancer Tumors by Activating CSF-1-Mediated Macrophage Infiltration.
Interplay between tumor cells and host cells in the tumor microenvironment dictates the development of all cancers. In breast cancer, malignant cells educate host macrophages to adopt a protumorigenic phenotype. In this study, we show how the integrin-regulatory protein kindlin-2 (FERMT2) promotes metastatic progression of breast cancer through the recruitment and subversion of host macrophages. Kindlin-2 expression was elevated in breast cancer biopsy tissues where its levels correlated with reduced patient survival. On the basis of these observations, we used CRISPR/Cas9 technology to ablate Kindlin-2 expression in human MDA-MB-231 and murine 4T1 breast cancer cells. Kindlin-2 deficiency inhibited invasive and migratory properties in vitro without affecting proliferation rates. However, in vivo tumor outgrowth was inhibited by >80% in a manner associated with reduced macrophage infiltration and secretion of the macrophage attractant and growth factor colony-stimulating factor-1 (CSF-1). The observed loss of CSF-1 appeared to be caused by a more proximal deficiency in TGFβ-dependent signaling in Kindlin-2-deficient cells. Collectively, our results illuminate a Kindlin-2/TGFβ/CSF-1 signaling axis employed by breast cancer cells to capture host macrophage functions that drive tumor progression. Cancer Res; 77(18); 5129-41. ©2017 AACR.


A blind method for the estimation of the Hurst exponent in time series: theory and application.
Nowadays many methods for the estimation of self-similarity (Hurst coefficient, H) in time series are available. Most of them, even if very effective, need some a priori information to be applied. We analyzed the eight most used methods for H estimation (working both in time and in frequency). We tested these methods on data generated with four kinds of time series models (fBm and fGn generated iteratively with Feder algorithm, 1f(alpha), and the fractional autoregressive integrated moving-average) in the range 0.1<or=H<or=0.9. We evaluated the performances of each method in terms of accuracy (bias) and precision [standard deviation (STD)] of the deviation from the expected value. The paper proposes a procedure useful for a reliable estimation of H, using these existing methods, without any assumptions on the stationarity/nonstationarity of the time series, where for these types of processes the "nonstationarity" is mainly caused by the divergence of the variance with time. This procedure suggests that one performs, as a first step, the detrended fluctuations analysis, which provides an indication about stationarity of the series and is related to the properties of self-similarity and long correlations. The procedure then identifies the best method for the estimation of H, depending on this first estimation. As an example application, we use our procedure to evaluate the Hurst coefficient in microelectrode array neuronal recordings.


RIS-aided dynamically adaptive wide field-of-view receiver for visible light communication in industrial internet of things.
In the current visible light communication (VLC) system, a condenser lens is generally used in the front of receiver to achieve a higher data rate, making an extremely narrow field-of-view for the receiver. With the spread of Industrial Internet of Things (IIoT), the communication between mobile terminals is urgently required. A wide-range detecting method for VLC system in IIoT scenario is asked. In this paper, a novel self-adaptive wide-FoV receiver involving reconfigurable intelligent surfaces (RIS) is proposed. The effective detecting range of the receiver can be expanded by dynamically adjusting the incident light directions with the assistance of RIS. Based on the maximum arrived flux criterion, the mathematical model is established and the optimized RIS parameter tuning algorithm is presented. The feasibility and validity of the method are verified by simulation. The results show that the tolerable transceiver offset can be increased to 2∼4 times as the conventional receiver.


Repair of sublethal and potentially lethal radiation damage by rat embryos exposed to gamma rays or helium lons.
Embryonic survival was examined in rats exposed to a 24-hour split-dose regimen of gamma rays or extended-Bragg-peak (EBP) helium ions on the fifth and sixth days of gestation. The data indicate that EBP helium ions, which are known to have a single-dose relative biological effectiveness (RBE) of 1.0, exhibit a split-dose RBE of 1.5 with respect to embryo killing. Using an experimental rat embryo system, delayed implantation, it was also noted that the embryocidal damage induced by EBP helium ions contains a smaller potentially lethal component than that induced by gamma rays.


Secondary reduction mammaplasty: does initial pedicle design matter?
Reduction mammaplasty is one of the most common plastic surgical procedures performed in the United States. Occasionally patients will require a second reduction to address persistent or recurrent symptomatic macromastia. When the vascular pedicle of a primary breast reduction is unknown, there is uncertainty regarding how best to proceed with a secondary reduction. When the pedicle is known, we include at least the primary pedicle in our operative plan. When unknown, we performed a modified central mound (MCM) reduction technique. The MCM reduction respects the blood supply to the nipple-areolar complex (NAC) by preserving any remaining vascularity that is present within the central mound tissue while also maintaining superior and inferior vascular pedicles. We avoid using a free nipple graft.Thirty patients (60 breasts) underwent repeat breast reductions between 2009 and 2016. Patients were placed into two groups whether their primary vascular pedicle was known or unknown, and then further grouped based on the type of reduction they received. There was no significant difference in the complication rate between patients that underwent an MCM reduction versus those that underwent reduction with other techniques. Most patients maintained breast sensation and none required a free nipple graft.Patients can be offered repeat reduction mammaplasty with the possibility of nipple sensation preservation and a normal-appearing NAC regardless if the primary vascular pedicle is known. If the primary pedicle is unknown, the MCM technique is an excellent option.


Space technology and the optical sciences.
The earth-orbiting satellites and the deep-space probes have provided for the optical sciences platforms from which to study the earth, the solar system, and the universe with truly revolutionary capability. For the terrestrial sciences the orbiting platforms for optical measurements in both low and geostationary orbits have given us a view of our planet and a global coverage never before possible. For the astronomical applications of optical instruments that "cataract of the telescopic eye," the atmosphere of the earth has been left behind and through proximity, including actual contact, we now have resolution and spectral coverage limited only by money and motive.


Correlating chemistry and mass transport in sustainable iron production.
Steelmaking contributes 8% to the total CO2 emissions globally, primarily due to coal-based iron ore reduction. Clean hydrogen-based ironmaking has variable performance because the dominant gas-solid reduction mechanism is set by the defects and pores inside the mm- to nm-sized oxide particles that change significantly as the reaction progresses. While these governing dynamics are essential to establish continuous flow of iron and its ores through reactors, the direct link between agglomeration and chemistry is still contested due to missing measurements. In this work, we directly measure the connection between chemistry and agglomeration in the smallest iron oxides relevant to magnetite ores. Using synthesized spherical 10-nm magnetite particles reacting in H2, we resolve the formation and consumption of wüstite (Fe1-xO)-the step most commonly attributed to whiskering. Using X-ray diffraction, we resolve crystallographic anisotropy in the rate of the initial reaction. Complementary imaging demonstrated how the particles self-assemble, subsequently react, and grow into elongated "whisker" structures. Our insights into how morphologically uniform iron oxide particles react and agglomerate in H2 reduction enable future size-dependent models to effectively describe the multiscale aspects of iron ore reduction.


Endovascular management of chronic symptomatic aortic dissection with the Streamliner Multilayer Flow Modulator: Twelve-month outcomes from the global registry.
Reported are initial 12-month outcomes of patients with chronic symptomatic aortic dissection managed by the Streamliner Multilayer Flow Modulator (SMFM; Cardiatis, Isnes, Belgium). Primary end points were freedom from rupture- and aortic-related death, and reduction in false lumen index. Secondary end points were patency of great vessels and visceral branches, and freedom of stroke, paraplegia, and renal failure. Out of 876 SMFM implanted globally, we have knowledge of 542. To date, 312 patients are maintained in the global registry, of which 38 patients were identified as having an aortic dissection (12.2%). Indications included 35 Stanford type B dissections, two Stanford type A and B dissections, and one mycotic Stanford type B dissection. There were no reported ruptures or aortic-related deaths. All cause survival was 85.3% Twelve-month freedom from neurologic events was 100%, and there were no incidences of end-organ ischemia, paraplegia or renal insult. Morphologic analysis exhibited dissection remodeling by a reduction in longitudinal length of the dissected aorta, and false lumen volume. A statistically significant reduction in false lumen index (P = .016) at 12 months, and a borderline significant increase in true lumen volume (P = .053) confirmed dissection remodeling. The SMFM is an option in management of complex pan-aortic dissection. Results highlight SMFM implantation leads to dissection stabilization with no further aneurysm progression, and no retrograde type A dissection. Thoracic endovascular aneurysm repair by SMFM ensued in freedom from aortic rupture, neurologic stroke, paraplegia and renal failure. Further analysis of the global registry data will inform long-term outcomes.


Hydrogen adsorption in carbon nanostructures: comparison of nanotubes, fibers, and coals.
Single-walled carbon nanotubes (SWNT) were reported to have record high hydrogen storage capacities at room temperature, indicating an interaction between hydrogen and carbon matrix that is stronger than known before. Here we present a study of the interaction of hydrogen with activated charcoal, carbon nanofibers, and SWNT that disproves these earlier reports. The hydrogen storage capacity of these materials correlates with the surface area of the material, the activated charcoal having the largest. The SWNT appear to have a relatively low accessible surface area due to bundling of the tubes; the hydrogen does not enter the voids between the tubes in the bundles. Pressure-temperature curves were used to estimate the interaction potential, which was found to be 580+/-60 K. Hydrogen gas was adsorbed in amounts up to 2 wt % only at low temperatures. Molecular rotations observed with neutron scattering indicate that molecular hydrogen is present, and no significant difference was found between the hydrogen molecules adsorbed in the different investigated materials. Results from density functional calculations show molecular hydrogen bonding to an aromatic C[bond]C that is present in the materials investigated. The claims of high storage capacities of SWNT related to their characteristic morphology are unjustified.


Sacrococcygeal teratomas in newborns: a comprehensive review for the radiologists.
Sacrococcygeal teratomas are the most common solid tumor in newborn infants. The diagnosis is not difficult in many cases; however, there should be additional information on imaging studies in order to manage those infants properly. Details include histology, morphologic classification, complications such as rupture, bleeding, and mass effects on the adjacent structures. Although imaging features cannot accurately predict the histologic subtypes of the tumors, thorough evaluation of the imaging features can help distinguish malignant tumors from benign tumors. In this article, pathogenesis, histological characteristics, clinical considerations, and morphologic characteristics will be discussed.


Scopoletin Improves Glucose Homeostasis in the High-Fructose High-Fat Diet-Induced Diabetes Model in Wistar Rats.
Antihyperglycemic action of scopoletin needs to be validated before considering it for clinical trials. The present study explored antihyperglycemic action of scopoletin in high-fructose high-fat diet (HFHFD)-induced diabetes in rats. The animal study was performed using 48 rats, 6 in each group. HFHFD was administered for model induction for 74 days. Rats in Group I (normal control [NC]) and group II (experimental control [EC]) received normal saline and HFHFD, respectively, throughout the study. Groups III, IV, V, and VI received oral scopoletin (1 mg/kg [low dose, LD], 5 mg/kg [medium dose, MD], 10 mg/kg [high dose, HD]), and metformin (250 mg/kg; positive control [PC] for efficacy), respectively, once daily from day 60 to 74, in addition to HFHFD. Group VII (10 mg/kg oral scopoletin safety group) and VIII (0.1 mg/kg oral warfarin; PC for safety) were separately used for bleeding time-clotting time (BTCT) assessment on days 60, 68, and 74. Groups I, VII, and VIII rats were studied for safety assessment. Later, animals were sacrificed for histological examination. Scopoletin-treated groups showed a significant decline in glucose levels, especially in the MD (5.18 ± 0.12) and HD group (5.271 ± 0.11) in comparison to the EC (6.37 ± 0.05) on day 74 (P < .05). Two weeks after scopoletin treatment, β-cell function significantly improved (53.073 ± 4.67) in the MD group versus 29.323 ± 8.505 in the NC group (P < .05). A statistically significant difference was observed when the MD group (53.07 ± 4.67) was compared to the metformin-treated group (24.80 ± 3.24; P < .05). The safety assessment in the form of BTCT findings did not observe a difference among groups I, VII, and VIII (P > .05). The study showed that scopoletin dose-independently reversed insulin resistance. Consequently, scopoletin can be a potential candidate for antidiabetic drug development.


A comparative study of fruit and vegetable consumption and physical activity among adolescents in 49 Low-and-Middle-Income Countries.
Physical inactivity and low consumption of fruits and vegetables (FV) during adolescence may persist through adulthood, putting adolescents at risk of developing chronic diseases. Although studies from high-income countries have reported differences in FV consumption and physical activity (PA) between adolescent boys and girls, few exist from low-and-middle-income countries (LMICs). In this study, we examined patterns of FV consumption and PA among adolescent boys and girls in LMICs. Country selection was based on availability of Global School-Based Student Health Survey (GSHS) data from 2004 to 2013. The total analytic sample was 164,771 adolescents from 49 LMICs. Descriptive statistics were generated to determine adolescents meeting the World Health Organization (WHO) recommendations for FV and PA. A Rao-Scott adjusted chi-square statistic was computed to assess gender differences. Less than 30% of adolescents across all countries met the WHO guidelines for FV consumption or PA. Morocco (29.5%) and India (29.5%) however had the highest percentage of adolescents meeting recommendations for FV and PA, respectively. Adolescent boys were more active than girls, and this difference was more notable in the Middle East and North African region. Adolescents achieving the WHO recommendations for daily consumption of FV and PA were consistently low in all countries.


Efficacy of a three-day prolonged-course of multiple-dose versus a single-dose of tranexamic acid in total hip and knee arthroplasty.
The application of tranexamic acid (TXA) in total hip arthroplasty (THA) and total knee arthroplasty (TKA) has brought momentous changes in blood management. However, the optimal regimen of TXA has not yet been identified. This study aimed to compare the efficacy of a three-day prolonged-course of multiple-dose of TXA with a single pre-operative dose of TXA in patients who undergo THA and TKA. We retrospectively analyzed two groups of consecutive patients who received primary unilateral THA and TKA from 2015 to 2017. One group received a three-day prolonged-course of multiple-dose of TXA, while another group received a single-dose of TXA. The primary outcomes included the changes in hemoglobin (Hb), estimated total blood loss (TBL), and transfusion rate; the secondary outcomes included the platelet (PLT) counts, inflammatory markers, and fibrinolysis parameters. A total of 193 THA and 166 TKA procedures were included for comparison. Compared with the patients who received a single-dose of TXA, the patients who received a three-day prolonged-course of multiple-dose of TXA had smaller post-operative drops in Hb levels, which led to consistently significantly higher Hb levels in both THA and TKA. Therefore, the use of multiple-dose of TXA was associated with significantly lower maximum Hb drops and estimated TBL in both THA (24.58±11.43 vs. 30.38±11.33 g/L, P=0.001; 685.88±412.02 vs. 968.94±479.9 mL, P<0.0001) and TKA (18.04±9.75 vs. 27.24±10.99 g/L, P<0.0001; 497.35±291.03 vs. 816.51±354.38 mL, P<0.0001), and marginally reduced transfusion requirements (THA: 1/65 vs. 10/128; TKA: 0/70 vs. 2/96). The multiple-dose group also showed higher PLT counts, continuously reduced inflammatory responses, and significantly and durably attenuated fibrinolytic responses. A three-day prolonged-course of multiple-dose of TXA was consistently effective in reducing post-operative Hb drops, estimated TBL, inflammatory responses, and fibrinolytic responses, which could be recommended for clinical practice. However, these findings need to be confirmed by prospective studies.


Effect of Unilateral Acoustic Trauma on Neuronal Firing Activity in the Inferior Colliculus of Mice.
Neural hyperactivity induced by sound exposure often correlates with the development of hyperacusis and/or tinnitus. In laboratory animals, hyperactivity is typically induced by unilateral sound exposure to preserve one ear for further testing of hearing performance. Most ascending fibers in the auditory system cross into the superior olivary complex and then ascend contralaterally. Therefore, unilateral exposure should be expected to mostly affect the contralateral side above the auditory brain stem. On the other hand, it is well known that a significant number of neurons have crossing fibers at every level of the auditory pathway, which may spread the effect of unilateral exposure onto the ipsilateral side. Here we demonstrate that unilateral sound exposure causes development of hyperactivity in both the contra and ipsilateral inferior colliculus in mice. We found that both the spontaneous firing rate and bursting activity were increased significantly compared to unexposed mice. The neurons with characteristic frequencies at or above the center frequency of exposure showed the greatest increase. Surprisingly, this increase was more pronounced in the ipsilateral inferior colliculus. This study highlights the importance of considering both ipsi- and contralateral effects in future studies utilizing unilateral sound exposure.


Pathological activity in mediodorsal thalamus of rats with spinal cord injury pain.
Spinal cord injury (SCI) results not only in motor deficits, but produces, in many patients, excruciating chronic pain (SCI pain). We have previously shown, in a rodent model, that SCI causes suppression of activity in the GABAergic nucleus, the zona incerta (ZI), and concomitant increased activity in one of its main targets, the posterior nucleus of the thalamus (PO); the increased PO activity is correlated with the maintenance and expression of hyperalgesia after SCI. Here, we test the hypothesis that SCI causes a similar pathological increase in other thalamic nuclei regulated by the ZI, specifically the mediodorsal thalamus (MD), which is involved in the emotional-affective aspects of pain. We recorded single and multiunit activity from MD of either anesthetized or awake rats, and compared data from rats with SCI with data from sham-operated controls (anesthetized experiments) or with data from the same animals prelesion (awake experiments). Consistent with our hypothesis, MD neurons from rats with SCI show significant increases in spontaneous firing rates and in the magnitude and duration of responses to noxious stimuli. In a subset of anesthetized animals, similar changes in activity of MD neurons were produced by pharmacologically inactivating ZI in naive rats, suggesting that the changes in the MD after SCI are related to suppressed inhibition from the ZI. These data support our hypothesis that SCI pain results, at least in part, from a loss of inhibition to thalamic nuclei associated with both the sensory-discriminative and emotional-affective components of pain.


H-NS: a modulator of environmentally regulated gene expression.
H-NS is a small chromatin-associated protein found in enterobacteria. H-NS has affinity for all types of nucleic acids but binds preferentially to intrinsically curved DNA. The major role of H-NS is to modulate the expression of a large number of genes, mostly by negatively affecting transcription. Many of the H-NS-modulated genes are regulated by environmental signals, and expression of most of these genes is positively regulated by specific transcription factors. Therefore one of the purposes of H-NS could be to repress expression of some genes under conditions characteristic of a non-intestinal environment, but allow expression of specific genes in response to certain stimuli in the intestinal environment. The hns gene is autoregulated. In vivo the H-NS to DNA ratio is fairly constant except during cold shock, when it increases three- to fourfold. In this review we propose that only the preferential binding to intrinsically curved DNA plays a role under normal growth conditions, and we discuss the different mechanisms by which H-NS might affect gene expression and how H-NS could be involved in the response to different stress situations. Finally, we summarize the evolutionary and functional relationship between H-NS and the homologous StpA.


Pirated Siderophores Promote Sporulation in Bacillus subtilis.
In microbial communities, bacteria chemically and physically interact with one another. Some of these interactions are mediated by secreted specialized metabolites that act as either intraspecies or interspecies signals to alter gene expression and to change cell physiology. Bacillus subtilis is a well-characterized soil microbe that can differentiate into multiple cell types, including metabolically dormant endospores. We were interested in identifying microbial interactions that affected sporulation in B. subtilis Using a fluorescent transcriptional reporter, we observed that coculturing B. subtilis with Escherichia coli promoted sporulation gene expression via a secreted metabolite. To identify the active compound, we screened the E. coli Keio Collection and identified the sporulation-accelerating cue as the siderophore enterobactin. B. subtilis has multiple iron acquisition systems that are used to take up the B. subtilis-produced siderophore bacillibactin, as well as to pirate exogenous siderophores such as enterobactin. While B. subtilis uses a single substrate binding protein (FeuA) to take up both bacillibactin and enterobactin, we discovered that it requires two distinct genes to sporulate in response to these siderophores (the esterase gene besA for bacillibactin and a putative esterase gene, ybbA, for enterobactin). In addition, we found that siderophores from a variety of other microbial species also promote sporulation in B. subtilis Our results thus demonstrate that siderophores can act not only as bacterial iron acquisition systems but also as interspecies cues that alter cellular development and accelerate sporulation in B. subtilisIMPORTANCE While much is known about the genetic regulation of Bacillus subtilis sporulation, little is understood about how other bacteria influence this process. This work describes an interaction between Escherichia coli and B. subtilis that accelerates sporulation in B. subtilis The interaction is mediated by the E. coli siderophore enterobactin; we show that other species' siderophores also promote sporulation gene expression in B. subtilis These results suggest that siderophores not only may supply bacteria with the mineral nutrient iron but also may play a role in bacterial interspecies signaling, providing a cue for sporulation. Siderophores are produced by many bacterial species and thus potentially play important roles in altering bacterial cell physiology in diverse environments.


Peripetrosal arachnoid cysts.
The present review summarizes the current theories on arachnoid cyst formation, the common presentations of cysts surrounding or eroding the temporal bone from the middle and posterior cranial fossae, the diagnostic strategies and the management considerations and options. Arachnoid cysts are most common in the middle cranial fossa and rarely present in association with the petrous apex. They are frequently found incidentally on imaging studies performed in the workup for unrelated symptoms. When they do cause symptoms, these are usually nonspecific. Thus it is important to establish the relationship between the two. Peripetrosal arachnoid cysts may cause cranial nerve deficits in addition to symptoms related to intracranial hypertension. Small asymptomatic cysts are managed conservatively with serial imaging. Large symptomatic cysts are often managed surgically with shunting, open excision or open or neuroendoscopic fenestration or marsupialization. The management of large asymptomatic cysts depends on the patient and cyst characteristics. Peripetrosal arachnoid cysts are often incidental findings. Careful selection of surgical candidates is of utmost importance. Multiple surgical options with similar success rates are available. The rates and profile of their complications may differ. Overall, approximately 70% of patients experience improvement in their symptoms with surgery.


Feather pecking and cannibalism in a caged layer flock.
1. The progress of feather pecking and cannibalism was recorded from hatching to end of lay in a flock of caged layers and the influence of group size, floor area allowance and cage tier upon the incidence of these activities during lay assessed. 2. The largest group suffered more cannibalism and feather pecking than smaller groups, floor area allowance and tier being less important factors. 3. A significant trend was found for one death from cannibalism to be followed by more in the same cage.4. It was concluded that feather pecking and cannibalism are separate phenomena, although the same cage conditions increased the incidence of both. 5. Cannibalism may be divided into vent pecking and cannibalism affecting other parts of the body, the former is independent of feather pecking and the latter, though usually preceded by feather pecking, is only indirectly associated with it.


Paradox response of frog muscle membrane to changes in external potassium.
Applying conventional microelectrode technique the anomalous behaviour of membrane potential in response to changes in [K+]o was demonstrated in normal and cevadine-treated muscles bathed in Cl- -free medium. Partial repolarization of the cevadine-depolarized membrane and reappearance of the slow membrane potential oscillation (SMPO) were induced by elevating [K+]o from 2.5 mM to 10-20 mM. Both effects were reversed by return to 2.5 mM [K+]o. The K-induced repolarization was markedly reduced by 20 mM Cs+, but not by 0.1 mM ouabain, 1 mM 4-aminopyridine, or 1 mM diethyl-pyrocarbonate. The elevation of [K+]o failed to repolarize muscle fibers that had been depolarized only to a small extent. No K-induced repolarization has been observed in Cl- -containing fluid. In cevadine-free experiments the omission of potassium from the extracellular space in Cl- -free solution hyperpolarized some of the fibers, while depolarized others. Strong electrical stimuli applied in zero K-zero Cl solution turned all the fibers into depolarized state; on returning to 2.5 mM [K+]o complete repolarization was achieved in most of the fibers. It has been concluded that the paradox response of the muscle membrane to changes in [K+]o can be attributed to the K-dependent conductance changes of the inward rectifier K channel providing an explanation for the plateau-formation of SMPO and for the existence of two stable levels of membrane potential of the skeletal muscle bathed in Cl- -free medium.


Glomerular lysosomal enzymes in aminonucleoside nephrosis.
Lysosomal hydrolases produce degradation of glomerular basement membrane and may play a key role in catabolism of glycoproteins of extracellular matrix in glomeruli. Therefore we investigated activities of some lysosomal enzymes and stability of lysosomes in glomeruli of normal and nephrotic rats. Nephrosis was induced in rats by single injections of puromycin aminonucleoside. In glomeruli from nephrotic rats we found lower activities of beta-fucosidase and arylsulfatase, but activity of acid phosphatase was higher compared with control rats. Osmotic stability of lysosomes measured by release of beta-glucuronidase was decreased in nephrotic rats. Abnormal activity of lysosomal enzymes and altered physiology of lysosomes in glomeruli may be a pathogenic factor in the altered glycoprotein metabolism in nephrotic syndrome and perhaps also in other glomerular diseases.


Skew Deviation: Case Report and Review of the Literature.
To present a patient with a sudden onset ocular tilt reaction (OTR) and review recent knowledge and evolving insights of the underlying pathophysiological mechanisms of skew deviation and OTR. A middle-aged hypertensive man who had previously suffered stroke with good recovery presented with sudden-onset double vision, slurred speech, ataxia, and a head tilt. Romberg test was positive. The patient denied having disturbances of visual acuity, eye pain, or recent trauma. The right eyeball was pushed upward. The patient complained of double vision in any gaze direction. Movements of the extraocular muscles (EOMs) in the horizontal plane were normal, whereas vertical version and convergence were not possible. We administered a Hess-Lancaster test, cover test, fundoscopic examination, Parks-Bielschowsky three-step test, upright-supine test, brain magnetic resonance imaging (MRI), transcranial doppler (TCD) ultrasonography, electrocardiogram (ECG), Holter monitor (24 h), and echocardiography. The Hess-Lancaster test showed superior rectus muscle and inferior obliquus muscle palsy to the left and rectus inferior muscle and superior obliquus muscle palsy to the right. The right eyeball fell behind when looking downward and the left eyeball when looking upward. Cover alternating test was positive from vertical, R/L. Examination of the ocular fundus showed incyclotorsion of elevated right eye and excyclotorsion of depressed eye. The Parks-Bielschowsky three-step test was negative. A brain MRI with gadolinium revealed a small zone of diffusion restriction in the medial portion of the right cerebral peduncle and right thalamus. There was a gradual improvement in the patient's neurological status following treatment. Skew deviation, a not uncommon clinical condition, should be promptly recognized when binocular vertical diplopia cannot be interpreted by trochlearis and oculomotor nerve lesion, myasthenia gravis, or orbital pathology. Maddox rod, cover test, Parks-Bielschowsky three-step, and other tests should help to establish the diagnosis. The prognosis depends on etiology, but it is commonly favorable; the majority of patients recover spontaneously after less than a year. More invasive management options should be discussed thereafter.


Influence of low air humidity and low root temperature on water uptake, growth and aquaporin expression in rice plants.
The effects of low air humidity and low root temperature (LRT) on water uptake, growth and aquaporin gene expression were investigated in rice plants. The daily transpiration of the plants grown at low humidity was 1.5- to 2-fold higher than that at high humidity. LRT at 13°C reduced transpiration, and the extent was larger at lower humidity. LRT also reduced total dry matter production and leaf area expansion, and the extent was again larger at lower humidity. These observations suggest that the suppression of plant growth by LRT is associated with water stress due to decreased water uptake ability of the root. On the other hand, the net assimilation rate was not affected by low humidity and LRT, and water use efficiency was larger for LRT. We found that low humidity induced coordinated up-regulation of many PIP and TIP aquaporin genes in both the leaves and the roots. Expression levels of two root-specific aquaporin genes, OsPIP2;4 and OsPIP2;5, were increased significantly after 6 and 13 d of LRT exposure. Taken together, we discuss the possibility that aquaporins are part of an integrated response of this crop to low air humidity and LRT.


The role of serum testosterone testing: routine hormone analysis is an essential part of the initial screening of men with erectile dysfunction.
As oral phosphodiesterase-5 inhibitor therapy has become the first-line treatment of erectile dysfunction (ED), common approaches in the evaluation of ED have been largely abandoned. Not only is routine hormone analysis no longer widely recommended, but most specialists perform serum testosterone level testing only in the most complex cases of ED. This article explores the rationale for including serum testosterone analysis as part of the initial screening of patients with ED. The use of routine serum testosterone testing is advocated for its efficacy in the diagnosis and treatment of hypogonadism and pituitary disorders associated with ED.


[Percutaneous closure of an right-left interatrial shunt acquired after pneumonectomy].
Right to left shunt through a patent foramen ovale after pneumonectomy is a rare complication. Its clinical presentation is a severe dyspnea with posture dependency. The diagnosis is easily confirmed by contrast echocardiography. The purpose of this article is to expose the interest of interventional catheterization and transcatheter closure. This method appears to be a viable alternative to surgery for those patients with precarious respiratory function.


Precise size distribution measurement of aerosol particles and fog droplets in the open atmosphere.
A precise measurement for the aerosol particle size distribution and fog droplet size distribution simultaneously in the open atmosphere is proposed. The extinction coefficient and small-angle forward scattering measurement are integrated into the detection for particle size distribution in the open atmosphere, and can achieve the fine detection of the particles in the atmosphere with radius between 0.1 to 30 μm. The key technology including optimal scattering angle in small-angle forward scattering measurement and optimal wavelengths selection are discussed and solved in detail. The fourteen different particle size distributions including aerosol size distributions and fog droplet size distributions are used for the determination of optimal forward scattering angle and wavelengths. The optimal forward scattering angle is calculated to be 1.1°. Seven wavelengths for extinction coefficients and five wavelengths for forward scattering coefficients are chosen for the retrieval of particle size distribution in the measurement. The regularization inversion of optical parameters for the retrieval of particle size distribution is described. The aerosol particle size distributions measured by particle spectrometer and actual fog particle size distributions are used for the method test and the reconstructions of particle size distributions. The inversion results show that the method can achieve the precise measurements of aerosol particle size distribution and fog droplet size distribution. The error influence on the inversion results of distributions is discussed. Based on the sensitivity analysis of inversion results, the feasibility of measurement in the real atmosphere is analyzed and discussed, and the scheme of detection system is provided.


Effect of Praval bhasma (Coral calx), a natural source of rich calcium on bone mineralization in rats.
Praval bhasma (PB; Coral calx) is a natural source of rich calcium widely used in traditional system of Indian medicine as a supplement in the treatment of variety of bone metabolic disorders associated with calcium deficiency. The present study was designed to investigate the inhibitory effects of Praval bhasma on the progress of bone loss induced by ovariectomy and concurrent calcium deficiency (CD-OVX). Twenty-four female rats were ovariectomized, 12 sham operated, divided into three groups of 12 each, fed on low calcium diet (0.04% Ca) and treated either with vehicle or Praval bhasma (65 mg/kg body weight, twice a day) for 16 weeks. Compared to sham rats, CD-OVX animals showed an increase in urinary excretion of calcium (Ca) and phosphorus (P), decreased femoral weight and density which were significantly reversed in Praval bhasma treated animals. Measurement of cortical bone morphometric indices by CT-scanning technique showed increased medullary width and cross-sectional area, decreased periosteal area (PA), combined cortical thickness (CCT) and cortical area (CA)/periosteal area in CD-OVX animals compared to sham and PB-treated group. Scanning electron microscopy (SEM) study revealed porous and erosive appearance of the distal femur at the epiphysis and reduced Ca:P ratio in CD-OVX animals compared to sham and PB-treated group. Ash weight, percent ash, ash Ca and ash P levels were lower in CD-OVX animals than in sham or PB group. Histological examination of decalcified femurs showed narrowed and disappearance of trabeculae and widened medullary spaces and decreased impact strength as measured by impact test in CD-OVX animals compared to sham and PB-treated group. The present study concludes that Praval bhasma is effective in the prevention of calcium and estrogen deficient bone loss and justify the continuing use of this ayurvedic preparation in traditional system of Indian medicine for management of bone metabolic disorders such as osteoporosis.


Horse haemoglobin phenotyping by agarose gel isoelectric focusing comparison of Thoroughbreds with other Equidae.
By using isoelectric focusing in thin agarose slab gels 1049 Thoroughbred, 82 Nooitgedachter, 45 Percheron and 244 horses of other breeds were examined. The numbers of other Equidae tested were 107 donkeys, 50 mules, 4 common zebras (Equus burchelli boehmi) and 8 mountain zebras (Equus zebra hartmannae). Phenotypic data are presented for all tested animals and gene frequencies are calculated for the horses.


[A case of advanced thoracic esophageal cancer with marked response to bleomycin absorbed on activated carbon particles (BLM-CH44), methotrexate, and cisplatin].
A 67-year-old women, who suffered from advanced esophageal cancer with left main bronchus and azygous vein involvement, was treated by combined administration of bleomycin absorbed on activated carbon particles (BLM-CH44, 10 mg/body), methotrexate (30 mg/body i.m.), and cisplatin (75 mg/body i.v.). BLM-CH44 was injected around tumor and total dose of BLM was 120 mg, that of MTX was 180 mg, and that of CDDP was 225 mg. After therapy, the sign of extra-esophageal spread disappeared and a radical operation was performed. Microscopically, the lesion of the esophagus was almost disappeared, and CH44 staining lymph node involvement was completely disappeared.


Home-based palliative care for children: the case for funding.
Paediatric palliative care services have grown up in response to local needs with the result that provision is patchy and in some areas non-existent. Funding for existing services comes from a variety of sources and in the case of teams funded in 2003 from The New Opportunities Fund, there is uncertainty about future provision as funding streams come to an end. This article illustrates how home-based palliative care achieves the objectives of the NHS Plan (DH 2000a) and makes the case for the continuation of paediatric palliative care teams already established through New Opportunities Fund (NOF) funding as these provide a ready made, quality service meeting the government agenda and addressing the needs of patients in a place and at a time to suit them.


Heat stable and urea resistant alkaline phosphatase in maternal neutrophils from normal and Down syndrome pregnancies.
Activity levels of total and placental alkaline phosphatase (AP) were determined in maternal serum and neutrophils of normal and Down syndrome pregnancies. The placental iso-enzyme (PAP) was identified by its relative stability to urea and heat. Significant increase in the activity of all iso-enzymes across gestational stages was observed in maternal sera of 28 normal pregnancies. However, in the neutrophil extracts of the same blood samples no differences were detected between trimesters. Another set of experiments was aimed at finding diagnostic differences of PAP activity in maternal neutrophils of normal and trisomy 21 affected pregnancies. No differences of heat stable AP activity were found in maternal samples of 19 normal and 19 Down syndrome affected pregnancies. Urea resistant AP proportions were also similar when measured after 40 minutes of exposure (13 samples in each group). However, a marginally significant increase was observed in the mean value of the Down syndrome affected samples, after 60 minutes of urea treatment. In view of the above results we conclude that neutrophil AP activity is not as yet a useful marker for the screening of trisomy 21 fetuses.


Defining core health services: the New Zealand experience.
The New Zealand health service has been extensively changed over the past four years, with the introduction of four new Regional Health Authorities, required to purchase services on behalf of the Government from a range of providers. In order to ensure fairness across the four regions a Core Services Committee has been set up to define which services must be purchased. However, no clear agreement has emerged about a "core" and no list, either positive (inclusions) or negative (exclusions), has been defined. Instead general criteria have been suggested and steps have been taken to consult the community on their priorities. This paper describes seven workshops run by the author in an effort to discover how the community would reach decisions on the rationing of scarce resources. The outcome of these workshops is that there is virtually no community support for an approach based on the social utility of individuals in need.


The Influence of Counterfactual Comparison on Fairness in Gain-Loss Contexts.
Fairness perceptions may be affected by counterfactual comparisons. Although certain studies using a two-player ultimatum game (UG) have shown that comparison with the proposers influences the responders' fairness perceptions in a gain context, the effect of counterfactual comparison in a UG with multiple responders or proposers remains unclear, especially in a loss context. To resolve these issues, this study used a modified three-player UG with multiple responders in Experiment 1 and multiple proposers in Experiment 2 to examine the influence of counterfactual comparison on fairness-related decision-making in gain and loss contexts. The two experiments consistently showed that regardless of the gain or loss context, the level of inequality of the offer and counterfactual comparison influenced acceptance rates (ARs), response times (RTs), and fairness ratings (FRs). If the offers that were received were better than the counterfactual offers, unequal offers were more likely to be accepted than equal offers, and participants were more likely to report higher FRs and to make decisions more quickly. In contrast, when the offers they received were worse than the counterfactual offers, participants were more likely to reject unequal offers than equal offers, reported lower FRs, and made decisions more slowly. These results demonstrate that responders' fairness perceptions are influenced by not only comparisons of the absolute amount of money that they would receive but also specific counterfactuals from other proposers or responders. These findings improve our understanding of fairness perceptions.


Thermographical measuring of the skin temperature using laser needle acupuncture in preterm neonates.
In children, laser acupuncture is used more often than needle acupuncture in Western countries, due to their aversion to needles. When applying laser acupuncture to premature babies and neonates, firstly the degree of the thermal increase to the skin has to be evaluated so as to guarantee safe application. The patients were premature neonates before their discharge from hospital. The measurements were carried out by means of a polygraphy while they were asleep shortly. The large intestine 4 acupoint (LI4, Hegu) was stimulated by a microlaser needle (10 mW, 685 nm) twice (5 and 10 min). Local thermographic pictures were taken with a thermal camera (Flir i5, Flir Systems Inc., Portland, USA), and the warmest point was determined and subsequently compared. The study included 10 premature neonates (7 male, 3 female). The measurements were carried out on the 33rd day of life (weight 2030 g, gestational age 36 + 3 weeks of pregnancy). In comparison to the initial temperature (32.9°C), after 5 minutes of stimulation (33.9°C) (P = 0.025) and also after 10 minutes of stimulation (34.0°C) (P = 0.01), there was found to be a significant increase in the skin temperature. The singular maximum value of 37.9°C bears a potential danger; however, compared to the local temperatures reached in transcutaneous blood gas measurements it appears not to entail any risks.


Examination in the Time of COVID-19-MCh Plastic Surgery Examination: How Did We Do It?
Background Many aspects of life have been changed, after the starting of the pandemic. Modifications and improvisation in our day-to-day activities is now a new norm. During the pandemic period, continuation academic activities and conductance of examination is difficult but essential. We are sharing our experience of conductance of MCh examination during the pandemic and preparations made. This article also discussed the future of surgical assessment examination, use of technology in surgical assessment changing times. Methods Procedural flow of the examination, Logistics and arrangements were planned and checked. Reliability and validity of questions were maintained by providing a similar set of questions and stepwise objective assessment. Assessment and feedback by the examinees and examiners on the pattern and conductance of examination were assessed by a Likert scale. Results We found, 73% agreed examination patterns were able to test the knowledge fairly. While 80 % believed the pattern was the same for all the candidates. All the stakeholders agreed the examination conducted in a Safe and stress-free atmosphere and use of technology helpful. Fifty- three % agreed the case scenarios correctly simulate the clinical presentations. Lastly, 66 % felt the examination process is adequate for summative assessment. Conclusions It is vital to reflect regarding the need for a uniform module to handle changing scenarios keeping the integrity and quality of the examination. Interactive screen, mannequin, and 3D model will be useful in the examination. In future, standardized examination modules for the surgical trainees will be required to perform a comprehensive assessment.


Screening proteinuria and hematuria in Malaysian children.
Screening for proteinuria and hematuria is important in the prevention of chronic renal disease. In Malaysia to date no such attempt has been made to establish the prevalence of proteinuria and hematuria. A total of 45,149 primary school children from three districts in Kelantan were screened for proteinuria and hematuria. They were 23,289 boys and 21,860 girls. The prevalence of abnormal urinary sediments after third screening was 0.17% ie 0.07% were in boys and 0.10% were in girls. The commonest abnormality was proteinuria (0.12%), followed by hematuria (0.03%) and combination of proteinuria and hematuria (0.02%). Hematuria was more commonly seen in girls compared to boys while proteinuria was seen in almost equal proportion in boys and girls. Despite screening large number of children the prevalence of asymptomatic proteinuria and hematuria was far lower than in an earlier reported study. Furthermore the majority had mild abnormalities.


An exercise program for shoulder disability.
In disabling conditions of the shoulder the involvement is either primary or secondary in origin. The primary disabilities are usually caused by sudden direct trauma or repeated minor traumata. Bursitis, tendonitis, and minor tears of the rotator cuff may result. The disabilities which arise secondarily are more difficult to treat and may have prolonged sequelae. Cervical radiculitis, infectious mononeuritis, cardiac disease, and cerebrovascular disease are common sources for secondary shoulder involvement. Pain and limitation of motion with loss of function are the presenting symptoms. The selection of a proper program of therapy is determined by the diagnosis. Primary conditions are responsive to the usual physical measures of moist heat, ultrasound, and the common exercises. Injections of local anesthestics or steroids and use of deep x-ray therapy may also be effective. The disabilities which arise secondarily are more difficult to treat and often become chronic and intolerably painful. In the author's experience, the most effective treatment for the secondarily induced shoulder problem is the combined use of moist heat of mild intensity, manual mobilization, neuromuscular facilitation, and a suitable home program of appropriate exercise.


Quality assurance in radiation therapy: clinical and physical aspects. Future plans: clinical.
On a national scale in Canada, the members of the Canadian Association of Radiologists, Section of Radiation Oncology, plan to continue their outcome analyses. Nevertheless, there is considerable activity within many of the cancer centers in establishing quality assurance for all aspects of clinical practice, not just related to the technique of radiation therapy. Studies from the Princess Margaret Hospital will be used as examples to illustrate the need for quality assurance in: (a) diagnosis and evaluation of patients; (b) decision making with respect to treatment; (c) technical components of radiation therapy; and (d) outcome analysis, particularly an analysis of failures. For the future, there are two major objectives related to quality assurance. One is related to those patients with cancers who have a high probability of being cured. In this situation, achieving optimal treatment must be the objective and quality assurance must be directed at determining what is optimal treatment. For those patients in whom cure is still not commonly reached, the objective will be to determine why failures are occurring and whether radiation therapy technique can decrease the relapse rate.


Wide cross-species RNA-Seq comparison reveals convergent molecular mechanisms involved in nickel hyperaccumulation across dicotyledons.
The Anthropocene epoch is associated with the spreading of metals in the environment increasing oxidative and genotoxic stress on organisms. Interestingly, c. 520 plant species growing on metalliferous soils acquired the capacity to accumulate and tolerate a tremendous amount of nickel in their shoots. The wide phylogenetic distribution of these species suggests that nickel hyperaccumulation evolved multiple times independently. However, the exact nature of these mechanisms and whether they have been recruited convergently in distant species is not known. To address these questions, we have developed a cross-species RNA-Seq approach combining differential gene expression analysis and cluster of orthologous group annotation to identify genes linked to nickel hyperaccumulation in distant plant families. Our analysis reveals candidate orthologous genes encoding convergent function involved in nickel hyperaccumulation, including the biosynthesis of specialized metabolites and cell wall organization. Our data also point out that the high expression of IREG/Ferroportin transporters recurrently emerged as a mechanism involved in nickel hyperaccumulation in plants. We further provide genetic evidence in the hyperaccumulator Noccaea caerulescens for the role of the NcIREG2 transporter in nickel sequestration in vacuoles. Our results provide molecular tools to better understand the mechanisms of nickel hyperaccumulation and study their evolution in plants.


Development of an interactive social media tool for parents with concerns about vaccines.
Describe a process for designing, building, and evaluating a theory-driven social media intervention tool to help reduce parental concerns about vaccination. We developed an interactive web-based tool using quantitative and qualitative methods (e.g., survey, focus groups, individual interviews, and usability testing). Survey results suggested that social media may represent an effective intervention tool to help parents make informed decisions about vaccination for their children. Focus groups and interviews revealed four main themes for development of the tool: Parents wanted information describing both benefits and risks of vaccination, transparency of sources of information, moderation of the tool by an expert, and ethnic and racial diversity in the visual display of people. Usability testing showed that parents were satisfied with the usability of the tool but had difficulty with performing some of the informational searches. Based on focus groups, interviews, and usability evaluations, we made additional revisions to the tool's content, design, functionality, and overall look and feel. Engaging parents at all stages of development is critical when designing a tool to address concerns about childhood vaccines. Although this can be both resource- and time-intensive, the redesigned tool is more likely to be accepted and used by parents. Next steps involve a formal evaluation through a randomized trial.


Towards a nanospecific approach for risk assessment.
In the current paper, a new strategy for risk assessment of nanomaterials is described, which builds upon previous project outcomes and is developed within the FP7 NANoREG project. NANoREG has the aim to develop, for the long term, new testing strategies adapted to a high number of nanomaterials where many factors can affect their environmental and health impact. In the proposed risk assessment strategy, approaches for (Quantitative) Structure Activity Relationships ((Q)SARs), grouping and read-across are integrated and expanded to guide the user how to prioritise those nanomaterial applications that may lead to high risks for human health. Furthermore, those aspects of exposure, kinetics and hazard assessment that are most likely to be influenced by the nanospecific properties of the material under assessment are identified. These aspects are summarised in six elements, which play a key role in the strategy: exposure potential, dissolution, nanomaterial transformation, accumulation, genotoxicity and immunotoxicity. With the current approach it is possible to identify those situations where the use of nanospecific grouping, read-across and (Q)SAR tools is likely to become feasible in the future, and to point towards the generation of the type of data that is needed for scientific justification, which may lead to regulatory acceptance of nanospecific applications of these tools.


Characterization, cDNA cloning and expression pattern of relaxin gene during embryogenesis of Danio rerio.
We report the identification, the cDNA cloning, the temporal and spatial expression pattern analysis of the rln gene in the zebrafish Danio rerio. The deduced Rln B and A domains show different evolutionary conservation. Rln B domain shows higher similarity when compared to zebrafish and human RLN3 B domain than human RLN1 and RLN2 B domain. Differently, the zebrafish Rln A domain shows relatively low amino acid sequence similarity when compared with the same sequences. The rln gene is transcribed both during embryogenesis and in adult organism, where higher transcript level has been particularly evidenced in the brain. Moreover, we provide the first description of rln spatial expression pattern during embryonic development. In particular, we show restricted transcript localization starting at the pharyngula stage in olfactory placode, branchial arch region, and in a cell cluster near to otic vesicle. In larval stage, new transcription territories have been detected in both neural and non-neural regions. In particular, in the brain, rln expression has been revealed in telencephalic region around anterior commissure, in the preoptic area, and in restricted rombencephalic cell clusters. Expression of rln gene in extra-neural territories has been detected in the pancreatic and thyroid gland regions. Danio rerio rln expression pattern analysis reveals shared features with the mammalian RLN gene, particularly in the brain, where it might have a role in the neurophysiological processes. In addition, expression in the thyroid and pancreas region suggests a function as a paracrine and endocrine hormone.


Dexmedetomidine Improves Postoperative Patient-Controlled Analgesia following Radical Mastectomy.
Acute postoperative pain following radical mastectomy is a high risk for prolonged convalescence and potential persistent pain in patients with breast cancer. The present study was designed to observe the effect of intraoperative use of dexmedetomidine on acute postoperative pain following radical mastectomy under general anesthesia. Forty-five patients were enrolled into the study and divided into two groups that were maintained with propofol/remifentanil/Ringer's solution or propofol/remifentanil/Dexmedetomidine followed by morphine-based patient-controlled analgesia. During the first 24 h following surgery, patients receiving dexmedetomine had lower NRS pain scores, decreased morphine consumption, longer time to first morphine request as well as a trending decreased incidence of adverse effects when compared to those received Ringer's solution. In conclusion, the present study finds that intraoperative use of dexmedetomidine could promote analgesic property of postoperative morphine.


Science and society: Development of the Asian Men's Health Report: challenges and opportunities.
Men have shorter life expectancy and higher mortality than women; however, only a few countries have dedicated men's health policies. Men's health reports can support the development of men's health policies. The 2013 Asian Men's Health Report (AMHR) systematically documents and compares the status of men's health across countries in Asia. The AMHR can be used as an exemplar to guide future men's health reports. The main challenges during creation of the AMHR were the lack of comprehensive health databases and the variety of data quality between countries. The AMHR revealed variations in mortality and morbidity across diseases, regions, and income groups, prompting a Delphi survey among men's health stakeholders to determine whether any dedicated men's health policies in Asia existed and to reach a consensus on the recommendations of men's health policies. The AMHR helped to promote men's health in Asia and across the world, generated research questions and collaborations, provided evidence to support development of men's health policies, identified the need to improve existing health databases, and developed a framework for the creation of other men's health reports.


Window renovation and exposure to lead--an observational study.
Renovation of windows in old houses has recently established itself as an industry. A recognizable occupational lead exposure exists, which has not been studied previously. To compare lead exposure amongst window renovators with other groups of lead-exposed workers. Using blood lead results measured at the Health and Safety Laboratory (HSL), Sheffield, comparisons were made between three cohorts: window renovation workers, all male workers monitored by HSL during the period 1999-2001 and 63 male subjects involved in chemical paint-stripping of wood. Both the window renovation and the wood-stripping cohorts show significantly higher blood lead distributions than the 'all workers' cohort (P < 0.001). A similar pattern was also found for comparison of the prevalence of subjects above the UK suspension level of 60 microg/dl (2.89 microM) (window renovation, P < 0.001; wood-stripping, P < 0.0001). Blood lead results at or above the suspension level in wood-strippers were significantly higher compared to window renovators (P = 0.034). Window renovation is shown to present a potential for significant lead exposure, and suspension from work under The Control of Lead at Work Regulations 2002. Two groups of risk factors predominate: the well-documented potential for release of lead from old paint, and the peripatetic nature of the work.


Emerging Role of Exosomes in Diagnosis and Treatment of Infectious and Inflammatory Bowel Diseases.
To communicate with each other, cells release exosomes that transfer their composition, including lipids, proteins and nucleic acids, to neighboring cells, thus playing a role in various pathophysiological processes. During an infection with pathogenic bacteria, such as adherent-invasive E. coli (AIEC) associated with Crohn disease, exosomes secreted by infected cells can have an impact on the innate immune responses of surrounding cells to infection. Furthermore, inflammation can be amplified via the exosomal shuttle during infection with pathogenic bacteria, which could contribute to the development of the associated disease. Since these vesicles can be released in various biological fluids, changes in exosomal content may provide a means for the identification of non-invasive biomarkers for infectious and inflammatory bowel diseases. Moreover, evidence suggests that exosomes could be used as vaccines to prime the immune system to recognize and kill invading pathogens, and as therapeutic components relieving intestinal inflammation. Here, we summarize the current knowledge on the role of exosomes in bacterial infections and highlight their potential use as biomarkers, vaccines and conveyers of therapeutic molecules in inflammatory bowel diseases.


Absorption/Transmission Measurements of PSAP Particle-Laden Filters from the Biomass Burning Observation Project (BBOP) Field Campaign.
Absorptivity measurements with a laser-heating approach, referred to as the laser-driven thermal reactor (LDTR), were carried out in the infrared and applied at ambient (laboratory) non-reacting conditions to particle-laden filters from a three-wavelength (visible) particle/soot absorption photometer (PSAP). The particles were obtained during the Biomass Burning Observation Project (BBOP) field campaign. The focus of this study was to determine the particle absorption coefficient from field-campaign filter samples using the LDTR approach, and compare results with other commercially available instrumentation (in this case with the PSAP, which has been compared with numerous other optical techniques). Advantages of the LDTR approach include 1) direct estimation of material absorption from temperature measurements (as opposed to resolving the difference between the measured reflection/scattering and transmission), 2) information on the filter optical properties, and 3) identification of the filter material effects on particle absorption (e.g., leading to particle absorption enhancement or shadowing). For measurements carried out under ambient conditions, the particle absorptivity is obtained with a thermocouple placed flush with the filter back surface and the laser probe beam impinging normal to the filter particle-laden surface. Thus, in principle one can employ a simple experimental arrangement to measure simultaneously both the transmissivity and absorptivity (at different discrete wavelengths) and ascertain the particle absorption coefficient. For this investigation, LDTR measurements were carried out with PSAP filters (pairs with both blank and exposed filters) from eight different days during the campaign, having relatively light but different particle loadings. The observed particles coating the filters were found to be carbonaceous (having broadband absorption characteristics). The LDTR absorption coefficient compared well with results from the PSAP. The analysis was also expanded to account for the filter fiber scattering on particle absorption in assessing particle absorption enhancement and shadowing effects. The results indicated that absorption enhancement effects were significant, and diminished with increased filter particle loading.


The effects of ageing on wound healing: immunolocalisation of growth factors and their receptors in a murine incisional model.
A number of reports suggest that the process of ageing impairs wound repair and that strategies to manipulate the age-related wound healing environment are necessary in order to stimulate repair. The process of cutaneous wound repair is controlled by growth factors in an autocrine and paracrine fashion: it is therefore surprising that the localisation of specific growth factors and their receptors has not been documented in wound healing with respect to chronological age. In this study the temporal profile of growth factor and receptor immunostaining was assessed within acute incisional wounds in an ageing mouse colony. A delay in appearance of platelet derived growth factor (PDGF) A and B isoforms, and PDGF-alpha and -beta receptors was evident with increasing animal age, paralleled by a similar finding for epidermal growth factor (EGF) and EGF receptor. Transforming growth factor (TGF)-beta 1 and 2 isoforms were increased at all time points in the wounds of younger animals, but the TGF-beta 3 isoform increased in intensity from d 7 postwounding in the old mice wounds, and basic fibroblast growth factor (bFGF) from d 14. The quantity and distribution patterns of the various growth factors and their receptors may explain the age-related differences in wound healing speed and quality, and possibly suggest new therapeutic targets for manipulating wound healing in the aged.


Statistical mechanical concepts in immunology.
Higher organisms, such as humans, have an adaptive immune system that usually enables them to successfully combat diverse (and evolving) microbial pathogens. The adaptive immune system is not preprogrammed to respond to prescribed pathogens. Yet it mounts pathogen-specific responses against diverse microbes and establishes memory of past infections (the basis of vaccination). Although major advances have been made in understanding pertinent molecular and cellular phenomena, the mechanistic principles that govern many aspects of an immune response are not known. We illustrate how complementary approaches from the physical and life sciences can help confront this challenge. Specifically, we describe work that brings together statistical mechanics and cell biology to shed light on how key molecular/cellular components of the adaptive immune system are selected to enable pathogen-specific responses. We hope these examples encourage physical chemists to work at this crossroad of disciplines where fundamental discoveries with implications for human health might be made.


Isolation and characterization of methanophenazine and function of phenazines in membrane-bound electron transport of Methanosarcina mazei Gö1.
A hydrophobic, redox-active component with a molecular mass of 538 Da was isolated from lyophilized membranes of Methanosarcina mazei Gö1 by extraction with isooctane. After purification on a high-performance liquid chromatography column, the chemical structure was analyzed by mass spectroscopy and nuclear magnetic resonance studies. The component was called methanophenazine and represents a 2-hydroxyphenazine derivative which is connected via an ether bridge to a polyisoprenoid side chain. Since methanophenazine was almost insoluble in aqueous buffers, water-soluble phenazine derivatives were tested for their ability to interact with membrane-bound enzymes involved in electron transport and energy conservation. The purified F42OH2 dehydrogenase from M. mazei Gö1 showed highest activity with 2-hydroxyphenazine and 2-bromophenazine as electron acceptors when F420H2 was added. Phenazine-1-carboxylic acid and phenazine proved to be less effective. The Km values for 2-hydroxyphenazine and phenazine were 35 and 250 microM, respectively. 2-Hydroxyphenazine was also reduced by molecular hydrogen catalyzed by an F420-nonreactive hydrogenase which is present in washed membrane preparations. Furthermore, the membrane-bound heterodisulfide reductase was able to use reduced 2-hydroxyphenazine as an electron donor for the reduction of CoB-S-S-CoM. Considering all these results, it is reasonable to assume that methanophenazine plays an important role in vivo in membrane-bound electron transport of M. mazei Gö1.


Evaluating and improving the practice of family-centered care.
Evaluating and improving the practice of family-centered care involves planning the evaluation effort collaboratively with families, gathering information from a variety of audiences, investigating the different arenas of family-centered care, following growth in family-centered practice over time, using a variety of evaluation approaches, and integrating evaluation with efforts to change toward family-centered approaches to care. Resources available to guide the evaluation effort include guidelines for reviewing written materials in a unit, program, clinic, or practice; written surveys and checklists; guidelines for focus groups or interviews; suggestions for using health care scenarios to gather information about family-centered approaches to care; and questions for nurses to use to reflect on their own practice.


Multicentre, open label, randomised controlled trial comparing intermittent versus daily treatment for non-cavitary nodular/bronchiectatic Mycobacterium avium complex lung disease with rifampicin, ethambutol and clarithromycin (iREC): study protocol.
Standard treatment for nodular/bronchiectatic Mycobacterium avium complex lung disease (NB MAC-LD), excluding severe-status cases, differs between Japan and other countries. Internationally, three-drug combination intermittent treatment (three times a week administration) with macrolide, ethambutol and rifampicin is recommended, but a daily treatment regimen is recommended in Japan. To date, no randomised controlled study directly comparing intermittent treatment with daily treatment has been performed. The purpose of this study is to investigate the usefulness of intermittent treatment. A total of 140 patients diagnosed with NB MAC-LD in Japan will be randomly assigned, in a 1:1 ratio, to intermittent treatment group or daily treatment group, and three-drug combination therapy with clarithromycin, rifampicin and ethambutol will be continued for 1 year. The primary endpoint is the proportion of patients requiring modification of the initial treatment regimen. Secondary endpoints are adverse events, sputum culture conversion, time to sputum culture conversion, improvement of chest CT findings, change in health-related quality of life score and development of clarithromycin resistance. This trial was approved by the National Hospital Organisation Review Board for Clinical Trials (Headquarters). The results of this study will be reported at a society meeting or published in a peer-review journal.


Physical interpretation of the quantum two-stream instability.
The unexpected features of the two-stream instability in electrostatic quantum plasmas are interpreted in terms of the coupling of approximate fast and slow waves. This is accomplished through the factorization of the dispersion relation into different sectors having positive or negative energy. Therefore, the concept of negative and positive energy waves is useful not only for classical, but for quantum plasmas as well. We discuss the limitations of the quantum two-stream model in view of the weak coupling assumption.


Pomolic acid inhibits metastasis of HER2 overexpressing breast cancer cells through inactivation of the ERK pathway.
Expression of the CXC chemokine receptor-4 (CXCR4), a G protein-coupled receptor, and HER2, a receptor tyrosine kinase, strongly correlates with tumor progression and metastatic potential of breast cancer cells. We report the identification of pomolic acid (PA) as a novel regulator of HER2 and CXCR4 expression. We found that PA downregulated the expression of HER2 and CXCR4 in SKBR3 cells in a dose- and time-dependent manner. When investigated for the molecular mechanism(s), it was found that the downregulation of HER2 and CXCR4 was not due to proteolytic degradation but rather to transcriptional regulation as indicated by downregulation of mRNA expression. Moreover, we show that PA inhibits phosphorylation of ERK and reduces NF-κB activation. Suppression of CXCR4 expression by PA correlated with the inhibition of CXCL12-induced invasion of HER2-overexpressing breast cancer cells. Overall, our results demonstrate for the first time that PA is a novel inhibitor of HER2 and CXCR4 expression via kinase pathways and may play a critical role in determining the metastatic potential of breast cancer cells.


Effects of intravenous immunoglobulins on peripheral blood mononuclear cell activation in vitro.
The therapeutic effects of intravenous immunoglobulins (IVIGs) on different chronic inflammatory and autoimmune diseases is well appreciated, though clinical studies with high-evidence levels are largely missing. Similar to the broad spectrum of diseases and their underlying etiopathogenic background, the mechanisms of action seem heterogenous and multifold. Several studies addressing in vitro and in vivo effects of IVIG on various immunological parameters have been described with partly contradictory results. In this study immunoglobulins and stabilizers present in commercial IVIG preparations were studied in regard to the in vitro proliferation and cytokine production of peripheral blood mononuclear cells when stimulated with phytohemagglutinin (PHA), interleukin 2, and tetanus toxoid. Whereas the immunoglobulins stimulate the proliferation of PBMCs and decrease IFNgamma secretion, stabilizers of IVIG seem to inhibit the proliferation of PBMCs while increasing the secretion of IFN gamma. These effects have to be taken into account when balancing the impact of IVIG dosage and infusion intervals and relating them to clinical side effects and therapeutic efficacy.


Medicinal cannabis in children and adolescents with autism spectrum disorder: A scoping review.
Autism spectrum disorder (ASD) is a neurodevelopmental condition estimated to affect 1 in 66 children in Canada and 1 in 270 individuals worldwide. As effective therapies for the management of ASD core and associated symptoms are limited, parents are increasingly turning to clinicians for advice regarding the use of medicinal cannabis to manage behavioural disturbances. The objective of this scoping review was to identify and map symptoms, outcomes and adverse events related to medicinal cannabis treatment for ASD-related behaviours. Ovid MEDLINE, Embase, CINAHL, PsycInfo, Web of Science Core Collection, Google Scholar and grey literature sources were searched up to 5 January 2020 for studies. Included studies met the following criteria: (1) investigate the use of medicinal cannabis, (2) at least 50% participants had ASD, (3) at least 50% of the study population was 0-18 years old and (4) any study design (published or unpublished). We identified eight completed and five ongoing studies meeting the inclusion criteria. All studies reported substantial behaviour and symptom improvement on medicinal cannabis, with 61% to 93% of subjects showing benefit. In the three studies reporting on concomitant psychotropic medication usage and with cannabis use, up to 80% of participants observed a reduction in concurrent medication use. Adverse events related to cannabis use were reported in up to 27% of participants related, and two participants had psychotic events. Early reports regarding medicinal cannabis in paediatric ASD symptom management are presented as positive; the evidence, however, is limited to very few retrospective cohort and observational studies. Evidence of safety and efficacy from prospective clinical trials is needed.