[Changes in parameters of Ascophyllum nodosum dark respiration induced by different salinities].
The changes in the rates of O2 consumption and CO2 release by Ascophyllum nodosum thalli in the dark were studied during a 12 day incubation at 34, 20, and 10/1000 salinity as well as at different pH. Depending on the initial pH of the medium, the algae demonstrated antipodal functional responses to the same salinities and, as a consequence, different capacity to overcome hypoosmotic stress. In addition, we observed a more pronounced effect of pH on the rate of O2 consumption than on the rate of CO2 release. Simultaneous desalination and acidification of the medium (pH 7-8) increased O2 consumption in the dark, which activated oxidative processes in the cells and increased their energy status. Forced pH stabilization (8.2) of the medium coupled with its desalination inhibited dark respiration of the algae, which, in our opinion, decreased their energy status. Specific manifestation of hypoosmotic stress and adaptation in A. nodosum are discussed considering the assumed differences in algal energy status.


Growth in amphibians.
The complex life history of many amphibians has been designed to take advantage of the resources of two completely different habitats. The aquatic free-living amphibian larva is different from the terrestrial adult regarding morphology, physiology and behavioural patterns. Therefore, in the life-time of an individual amphibian, two discontinuous growth stanzas are exhibited. The sigmoid growth model fits well with both stanzas. The rapid growth of the larval amphibian can be described by the double exponential Gompertz equation, whereas the slow growth process of the transformed amphibian can be described by the von Bertalanffy growth model. The bulk of amphibian growth occurs in the terrestrial phase and is not independent of size, age, sex and environmental conditions. The endocrine regulation of growth in amphibians is unique in the sense that the mechanism of pituitary action is different in aquatic and terrestrial phases.


Modeling of population kinetics of plasmas that are not in local thermodynamic equilibrium, using a versatile collisional-radiative model based on analytical rates.
We discuss the modeling of population kinetics of nonequilibrium steady-state plasmas using a collisional-radiative model and code based on analytical rates (ABAKO). ABAKO can be applied to low-to-high Z ions for a wide range of laboratory plasma conditions: coronal, local thermodynamic equilibrium or nonlocal thermodynamic equilibrium, and optically thin or thick plasmas. ABAKO combines a set of analytical approximations to atomic rates, which yield substantial savings in computer running time, still comparing well with more elaborate codes and experimental data. A simple approximation to calculate the electron capture cross section in terms of the collisional excitation cross section has been adapted to work in a detailed-configuration-accounting approach, thus allowing autoionizing states to be explicitly included in the kinetics in a fast and efficient way. Radiation transport effects in the atomic kinetics due to line trapping in the plasma are taken into account via geometry-dependent escape factors. Since the kinetics problem often involves very large sparse matrices, an iterative method is used to perform the matrix inversion. In order to illustrate the capabilities of the model, we present a number of results which show that the ABAKO compares well with customized models and simulations of ion population distribution. The utility of ABAKO for plasma spectroscopic applications is also outlined.


Experimental and computational insights into luminescence in atomically precise bimetallic Au6-nCun(MPA)5 (n = 0-2) clusters.
Bimetallic nanoclusters (NCs) have emerged as a new class of luminescent materials for potential applications in sensing, bio-imaging, and light-emitting diodes (LEDs). Here, we have synthesized gold-copper bimetallic nanoclusters (AuCu NCs) using a one-step co-reduction method and tuned the emission wavelength from 520 nm to 620 nm by changing the [Cu2+]/[Au3+] molar ratio. The quantum yield (QY) increases from 6% to 13% upon incorporation of the Cu atom in the Au NCs. MALDI-TOF mass spectrometric analysis reveals that the composition of the Au NCs is Au6(MPA)5, and the bimetallic nanocluster is Au4Cu2(MPA)5, where 3-mercaptopropionic acid (MPA) is used as the capping ligand. Furthermore, we investigated the optimized structures of the as-synthesized NCs using density functional theory (DFT) along with analysis of the preferable adsorption sites using Fukui functions. We report the HOMO-LUMO gap, which is consistent with the experimentally observed red shift in the UV-Vis absorption features of the Au NCs upon copper doping. XPS studies suggest the formation of intermixing of states between the 5d orbitals of Au and the 3d orbitals of Cu in the AuCu NCs after incorporating Cu atoms into the Au NCs, which is corroborated by the DFT calculations on electronic charge transfer from the Cu to the Au atom in the NCs. The coupling between Au(I) and Cu(I) facilitates the formation of a low-lying mixed Au(I)-Cu(I) energy state. This study elaborates on the impact of Cu doping on the excited-state relaxation dynamics of AuCu NCs.


Electronic structural information from Q-band ENDOR on the type 1 and type 2 copper liganding environment in wild-type and mutant forms of copper-containing nitrite reductase.
Q-band ENDOR elucidated proton and nitrogen hyperfine features to provide spin density information at ligands of blue-green Type 1 and catalytic Type 2 copper centers in nitrite reductase. The blue-green Type 1 center of nitrite reductase has a redox, electron-transfer role, and compared to the blue center of plastocyanin, it has the following structural differences: a shortened Cu-Smet bond length, a longer Cu-Scys bond length, and altered ligand-copper-ligand bond angles (Adman, E. T., Godden, J. W., and Turley, S. (1995) J. Biol. Chem. 270, 27458-27474). The hyperfine couplings of the two Type 1 histidine (N delta) ligands showed a larger percentage difference from each other in electron spin density than previously reported for other blue Type 1 proteins, while the cysteine beta-proton hyperfine couplings, a measure of unpaired p pi spin density on the liganding cysteine sulfur, showed a smaller electron spin density. A mutation of the Type 1 center, M182T, having the copper-liganding Met182 transformed to Thr182, caused the center to revert to an optically "blue" center, raised its redox potential by approximately 100 mV, and led to the loss of activity (prior paper). Surprisingly, in M182T there was no change from native Type 1 copper either in the histidine or cysteine hyperfine couplings or in g values and Cu nuclear hyperfine couplings. The conclusion is that the optical and redox alterations due to changed Type 1 methionine ligation need not be concurrent with electron spin delocalization changes in the HOMO as reported from its essential cysteine and histidines. A detailed picture of the nitrogen couplings from the three histidine (N epsilon) ligands of the Type 2 center indicated a substantial ( approximately 200%) electronic hyperfine inequivalence of one of the histidine nitrogens from the other two within the Type 2 HOMO and thus provided evidence for electronic distortion of the Type 2 site. In the presence of the nitrite substrate, hyperfine couplings of all histidines diminished. We suggest that this nitrite-induced decreased covalency would correlate with an increased Type 2 redox potential to assist electron transfer to the Type 2 center. Dipole-coupled, angle-selected exchangeable proton features, observed over a range of g values, predicted a ligand-water proton distance of 2.80 A from copper, and these water protons were eliminated by nitrite. His287 is not a Type 2 ligand but is positioned to perturb an axial water or a nitrite of Type 2 copper. In the presence of nitrite the mutant H287E showed no evidence for the loss of water protons and no diminished ligand histidine covalency. H287E has vastly diminished activity (prior paper), and the ENDOR information is that NO2- does not bind to Type 2 copper of H287E. In summary, the electronic information from this study of native and suitably chosen mutants provided a test of the highest occupied molecular orbital (HOMO) wave function at Type 1 and Type 2 coppers and an intimate electronic insight into functional enzymatic properties.


The orphan nuclear receptor NR4A1 specifies a distinct subpopulation of quiescent myeloid-biased long-term HSCs.
Hematopoiesis is maintained throughout life by self-renewing hematopoietic stem cells (HSCs) that differentiate to produce both myeloid and lymphoid cells. The NR4A family of orphan nuclear receptors, which regulates cell fate in many tissues, appears to play a key role in HSC proliferation and differentiation. Using a NR4A1(GFP) BAC transgenic reporter mouse we have investigated NR4A1 expression and its regulation in early hematopoiesis. We show that NR4A1 is most highly expressed in a subset of Lin(-) Sca-1(+) c-Kit(+) CD48(-) CD150(+) long-term (LT) HSCs, and its expression is tightly associated with HSC quiescence. We also show that NR4A1 expression in HSCs is induced by PGE2, a known enhancer of stem cell engraftment potential. Finally, we find that both NR4A1(GFP+) and NR4A1(GFP-) HSCs successfully engraft primary and secondary irradiated hosts; however, NR4A1(GFP+) HSCs are distinctly myeloid-biased. These results show that NR4A1 expression identifies a highly quiescent and distinct population of myeloid-biased LT-HSCs.


Prevalence of posterior staphyloma and factors associated with its shape in the Japanese population.
Myopia is increasing rapidly worldwide. We performed a cross-sectional study to investigate the prevalence of posterior staphyloma, a complication of myopia, and its shape characteristics in relation to age, sex, and axial length (AL) in a Japanese community-based cohort. The right eyes of 3748 participants who underwent fundus photography and optical coherence tomography (OCT) examination were evaluated. Posterior staphyloma prevalence was evaluated using fundus photographs and OCT images. Furthermore, fundus shapes were analyzed by measuring local fundus curvatures on 6 mm cross-line OCT images at intervals of 1 µm. The mean and variance of the curvatures were calculated to represent the fundus shape of each eye for investigation of the relationship between fundus curvature and age, sex, and AL. Seventy-seven eyes (2.05%) had posterior staphyloma. The mean and variance of the fundus curvatures were significantly greater in women than in men and became greater with age, suggesting that the shape of the staphyloma was steeper and less smooth in women and elderly subjects. AL and mean curvature showed a significant correlation (P = 2 × 10-16, R = 0.480), which was significantly affected by age (P < 2 × 10-16). Quantitative analysis of fundus shapes was useful for statistical analysis of posterior staphyloma in relation to age, sex, and AL.


Mammary gland development in adult mice requires epithelial and stromal estrogen receptor alpha.
Complete mammary gland development takes place following puberty and depends on the estrogen receptor (ER)alpha and the progesterone receptor (PR) and is tightly regulated by the interaction of the mammary epithelium with the stromal compartment. Studies using mammary tissues of immature mice have indicated that stromal but not epithelial ER alpha is required for mammary gland growth. This study investigates whether these same tissue growth requirements of neonate tissue are necessary for mammary development and response in adult mice. Mammary epithelial cells were isolated from adult mice with a targeted disruption of the ER alpha gene (alpha ERKO) or from wild-type counterparts and injected into epithelial-free mammary fat pads of 3-wk-old female alpha ERKO or wild-type mice. Ten weeks after cell injection, analysis of mammary gland whole mounts showed that both stromal and epithelial ER alpha were required for complete mammary gland development in adult mice. However, when the mice were treated with high doses of estradiol (E2) and progesterone, stromal ER alpha was sufficient to generate full mammary gland growth. Surprisingly, ER alpha-deficient epithelial cells were able to proliferate and develop into a rudimentary mammary ductal structure in an ER alpha-negative stroma, indicating that neither stromal nor epithelial ER alpha are required for the mammary rudiment to form in the adult mouse, as confirmed by the phenotype of the alpha ERKO mammary gland. Use of this in vivo model system has demonstrated that neonatal and adult mammary tissues use a different tissue-specific role for ER alpha in mammary response. Immunostaining for ER alpha and PR in the mammary outgrowths supported the view that both stromal and epithelial ER alpha, in cooperation with epithelial PR, govern mammary gland development in adult mice.


Prospective associations between sedentary lifestyle and BMI in midlife.
A strong positive cross-sectional relationship between BMI and a sedentary lifestyle has been consistently observed in numerous studies. However, it has been questioned whether high BMI is a determinant or a consequence of a sedentary lifestyle. Using data from four follow-ups of the University of North Carolina Alumni Heart Study, we examined the prospective associations between BMI and sedentary lifestyle in a cohort of 4595 middle-aged men and women who had responded to questionnaires at the ages of 41 (standard deviation 2.3), 44 (2.3), 46 (2.0), and 54 (2.0). BMI was consistently related to increased risk of becoming sedentary in both men and women. The odds ratios of becoming sedentary as predicted by BMI were 1.04 (95% confidence limits, 1.00, 1.07) per 1 kg/m(2) from ages 41 to 44, 1.10 (1.07, 1.14) from ages 44 to 46, and 1.12 (1.08, 1.17) from ages 46 to 54. Controlling for concurrent changes in BMI marginally attenuated the effects. Sedentary lifestyle did not predict changes in BMI, except when concurrent changes in physical activity were taken into account (p < 0.001). The findings were not confounded by preceding changes in BMI or physical activity, age, smoking habits, or sex. Our findings suggest that a high BMI is a determinant of a sedentary lifestyle but did not provide unambiguous evidence for an effect of sedentary lifestyle on weight gain.


[The research on the system of prevention of spread of epidemics by rail transfer in China from 1910 to 1937].
The rail epidemic system to prevent the spread of plague began during the plague epidemic in northeast China in 1910. The laws and institutions of epidemic prevention evolved and were instituted following the development of the epidemic situation to control it. After the establishment of the Railways Ministry of the National Government in Nanjing, the rail epidemic prevention system was gradually perfected. The emergency measures and prevention measures conducted played a positive and effective role in the course of preventing the spread of the plague by trains.


Comparative Analysis of Metabolic Compositions and Trace Elements of Inonotus hispidus Mushroom Grown on Five Different Tree Species.
Inonotus hispidus is a popular edible and medicinal mushroom widely used in China. I. hispidus mushroom mainly grows on five different tree species (Morus alba L., Ulmus macrocarpa Hance, Fraxinus mandshurica Rupr., Ziziphus jujuba Mill., and Malus pumila Mill.), and their fruiting bodies were all separately used in the market. However, there is no holistic insight to elucidate the molecular basis of the differentiated usage. This study aimed to investigate and compare the metabolite compositions and trace elements in I. hispidus grown on five different tree species. The metabolomic data, 8 kinds of principal components and 12 kinds of trace elements, were analyzed in this study. The results showed that the same 1353 metabolites were identified in I. hispidus grown on five different tree species, but the relative abundance was different. The principal components and trace elements contents are different, for example, polysaccharides, phenol metabolites, Ca, Na, Mg, Fe, and Mn were enriched in I. hispidus grown on M. alba, the flavonoids were enriched in Z. jujuba samples, and the steroids, terpenoids, and Zn were enriched in M. pumila samples. Further, the KEGG enrichment pathway and metabolic models were established. These findings provide a molecular basis for the unique use of the I. hispidus mushroom grown on different tree species.


Identifying frailty risk profiles of home-dwelling older people: focus on sociodemographic and socioeconomic characteristics.
This paper investigates risk profiles of frailty among older people, as these are essential for detecting those individuals at risk for adverse outcomes and to undertake specific preventive actions. Frailty is not only a physical problem, but also refers to emotional, social, and environmental hazards. Using data generated from the Belgian Ageing Studies, a cross-sectional study (n = 28,049), we tested a multivariate regression model that included sociodemographic and socioeconomic indicators as well as four dimensions of frailty, for men and women separately. The findings indicated that for both men and women, increased age, having no partner, having moved house in the previous 10 years, having a lower educational level and having a lower household income are risk characteristics for frailty. Moreover, when looking at the different frailty domains, different risk profiles arose, and gender-specific risk characteristics were detected. This paper elaborates on practical implications, and formulates a number of future research recommendations to tackle frailty in an aging society. The conclusion demonstrates the necessity for a thorough knowledge of risk profiles of frailty, as this will save both time and money and permit preventive actions to be more individually tailored.


[Microbial community of municipal discharges in a sewage treatment plant].
There are numerous microorganisms, especial pathogens, in the discharges. Those microorganisms are discharged into the river and sea through sewage outfalls, which results in possible health risks to coastal populations. And more attention should be paid to municipal discharges in developing countries. This study investigated the microbial community in the discharges by constructing 16S rDNA clones library and using the PCR-RFLP technology. Phylogenetic analysis of bacteria in municipal discharges showed that there were 59 species, which were divided into 11 classes. Proteobacteria accounted for 85% of all the bacteria, of which β-Proteobacteria and γ- Proteobacteria were the dominant classes. Bacteria in the waste water treating process had important influence on microbial community in municipal discharges, therefore, municipal sewage plant should choose the process according to the characteristics and purifying capacity of the receiving water body. Legionella spp. accounted for approximately 10% , the Legionnaires' disease resulted from which might be of top risk for the residents in the surrounding of the municipal discharges outfall and receiving water. Dechloromonas aromatica could make use of chlorite ( CIO - ) , which led to its survival from chlorine disinfection, and it alerted us that several disinfection methods should be used together to ensure the bacterial safety of municipal discharges. Coliform group and other pathogenic bacteria, such as Salmonella spp. , Shigella spp. , Escherichia coli, Vibrio cholerae, Staphylococcus aureus, Arcobacter spp. were not detected in this study, and it indicated that we should do more work and use more methods to investigate the perniciousness of discharges.


RgC3H Involves in the Biosynthesis of Allelopathic Phenolic Acids and Alters Their Release Amount in Rehmannia glutinosa Roots.
Rehmannia glutinosa production is affected by replanting disease, in which autotoxic harm to plants is mediated by endogenous phenolic acids as allelopathic compounds found in root exudates. These phenolic acids are mostly phenylpropanoid products of plants' secondary metabolisms. The molecular mechanism of their biosynthesis and release has not been explored in R. glutinosa. P-coumarate-3-hydroxylase (C3H) is the second hydroxylase gene involved in the phenolic acid/phenylpropanoid biosynthesis pathways. C3Hs have been functionally characterized in several plants. However, limited information is available on the C3H gene in R. glutinosa. Here, we identified a putative RgC3H gene and predicted its potential function by in silico analysis and subcellular localization. Overexpression or repression of RgC3H in the transgenic R. glutinosa roots indicated that the gene was involved in allelopathic phenolic biosynthesis. Moreover, we found that these phenolic acid release amount of the transgenic R. glutinosa roots were altered, implying that RgC3H positively promotes their release via the molecular networks of the activated phenolic acid/phenylpropanoid pathways. This study revealed that RgC3H plays roles in the biosynthesis and release of allelopathic phenolic acids in R. glutinosa roots, laying a basis for further clarifying the molecular mechanism of the replanting disease development.


Influence of green grass-based diets on growth and reproductive performance in dairy heifers.
The objective of this study was to monitor the changes in growth, dry matter intake, and blood profiles (nutrition and reproductive hormones) of dairy heifers in response to green grass-based diets. Twelve crossbred heifers were equally divided into group 1: rice straw and concentrate; group 2: rice straw, green grass, and concentrate; group 3: green grass and concentrate; group 4: green grass, soybean hay, and concentrate. Dry matter intake in group 4 was found 6% higher (P < 0.05) than group 1. Negative body weight gain was found in group 1 and group 2 showed 14% higher body weight gain per 30 days compared to groups 3 and 4 (P < 0.05). Heifers in group 4 had significantly (P < 0.05) higher heart girth gain, serum albumin, urea, and blood urea nitrogen than the heifers in other groups. Endocrine parameters were found similar among groups. Overall, supply of green grass especially a mix of leguminous and non-leguminous was found advantageous in heifer feeding.


Incidence and risk of central nervous system metastases as site of first recurrence in patients with HER2-positive breast cancer treated with adjuvant trastuzumab.
Central nervous system (CNS) disease as the site of first relapse after exposure to adjuvant trastuzumab has been reported. We carried out comprehensive meta-analysis to determine the risk of CNS metastases as the first site of recurrence in patients with HER2-positive breast cancer who received adjuvant trastuzumab. Eligible studies include randomized trials of adjuvant trastuzumab administered for 1 year to patients with HER2-positive breast cancer who reported CNS metastases as first site of disease recurrence. Statistical analyses were conducted to calculate the incidence, relative risk (RR), and 95% confidence intervals (CIs) using fixed-effects inverse variance and random-effects models. A total of 9020 patients were included. The incidence of CNS metastases as first site of disease recurrence in HER2-positive patients receiving adjuvant trastuzumab was 2.56% (95% CI 2.07% to 3.01%) compared with 1.94% (95% CI 1.54% to 2.38%) in HER2-positive patients who did not receive adjuvant trastuzumab. The RR of the CNS as first site of relapse in trastuzumab-treated patients was 1.35 (95% CI 1.02-1.78, P = 0.038) compared with control arms without trastuzumab therapy. The ratio of CNS metastases to total number of recurrence events was 16.94% (95% CI 10.85% to 24.07%) and 8.33% (95% CI 6.49% to 10.86%) for the trastuzumab-treated and control groups, respectively. No statistically significant differences were found based on trastuzumab schedule or median follow-up time. No evidence of publication bias was observed. Adjuvant trastuzumab is associated with a significant increased risk of CNS metastases as the site of first recurrence in HER2-positive breast cancer patients.


Clinical evaluation of three respiratory gating schemes for different respiratory patterns on cardiac SPECT.
Respiratory gating reduces respiratory blur in cardiac single photon emission computed tomography (SPECT). It can be implemented as three gating schemes: (a) equal amplitude-based gating (AG); (b) phase or time-based gating (TG); or (c) equal count-based gating (CG), that is, a variant of amplitude-based method. The goal of this study is to evaluate the effectiveness of these respiratory gating methods for patients with different respiratory patterns in myocardial perfusion SPECT. We reviewed 1274 anonymized patient respiratory traces obtained via the Vicon motion-tracking system during their 99m Tc-sestamibi SPECT scans and grouped them into four breathing categories: (a) regular respiration (RR); (b) periodic respiration (PR); (c) respiration with apnea (AR); and (d) unclassified respiration (UR). For each respiratory pattern, 15 patients were randomly selected and their list-mode data were rebinned using the three gating schemes. A preliminary reconstruction was performed for each gate with the heart region segmented and registered to a reference gate to estimate the respiratory motion. A final reconstruction incorporating respiratory motion correction was done to get a final image set. The estimated respiratory motion, the full-width-at-half-maxima (FWHM) measured across the image intensity profile of the left ventricle wall, as well as the normalized standard deviation measured in a uniform cuboid region of the thorax were analyzed. There are 47.1%, 24.3%, 13.5%, and 15.1% RR, PR, AR, and UR patients, respectively, among the 1274 patients in this study. The differences among the three gating schemes in RR were smaller than other respiratory patterns. The AG and CG methods showed statistically larger motion estimation than TG particularly in the AR and PR patterns. Noise of AG varied more in different gates, especially for AR and UR patterns. More than half of the patients reviewed exhibited nonregular breathing patterns. Amplitude-based gating, that is, AG and CG, is a preferred gating method for such patterns and is a robust respiratory gating implementation method given the respiratory pattern of the patients is unknown before data acquisition. Phase gating is also a feasible option for regular respiratory pattern.


Processing deficits of motion of contrast-modulated gratings in anisometropic amblyopia.
Several studies have indicated substantial processing deficits for static second-order stimuli in amblyopia. However, less is known about the perception of second-order moving gratings. To investigate this issue, we measured the contrast sensitivity for second-order (contrast-modulated) moving gratings in seven anisometropic amblyopes and ten normal controls. The measurements were performed with non-equated carriers and a series of equated carriers. For comparison, the sensitivity for first-order motion and static second-order stimuli was also measured. Most of the amblyopic eyes (AEs) showed reduced sensitivity for second-order moving gratings relative to their non-amblyopic eyes (NAEs) and the dominant eyes (CEs) of normal control subjects, even when the detectability of the noise carriers was carefully controlled, suggesting substantial processing deficits of motion of contrast-modulated gratings in anisometropic amblyopia. In contrast, the non-amblyopic eyes of the anisometropic amblyopes were relatively spared. As a group, NAEs showed statistically comparable performance to CEs. We also found that contrast sensitivity for static second-order stimuli was strongly impaired in AEs and part of the NAEs of anisometropic amblyopes, consistent with previous studies. In addition, some amblyopes showed impaired performance in perception of static second-order stimuli but not in that of second-order moving gratings. These results may suggest a dissociation between the processing of static and moving second-order gratings in anisometropic amblyopia.


Home disadvantage in professional ice hockey.
Occurrence of the home field disadvantage in professional ice hockey was examined by analyzing data on penalty shots from 1983-2004. This datum was used as it does not involve physical contact for only the player taking the penalty shot is involved in the outcome. As a result, inhibition of anxiety associated with physical contact should not occur, and diffusion of responsibility would not occur since only the shooter is involved. Analysis indicated the player who took the penalty shot did not make significantly fewer shots at home than in away games. The result did not support hypotheses about roles of physical contact and diffusion of responsibility in accounting for past failures to find the home disadvantage in professional ice hockey.


Theory of scanning tunneling spectroscopy of magnetic adatoms in graphene.
We examine theoretically the signatures of magnetic adatoms in graphene probed by scanning tunneling spectroscopy (STS). When the adatom hybridizes equally with the two graphene sublattices, the broadening of the local adatom level is anomalous and can scale with the cube of the energy. In contrast to ordinary metal surfaces, the adatom local moment can be suppressed by the proximity of the probing scanning tip. We propose that the dependence of the tunneling conductance on the distance between the tip and the adatom can provide a clear signature for the presence of local magnetic moments. We also show that tunneling conductance can distinguish whether the adatom is located on top of a carbon atom or in the center of a honeycomb hexagon.


Magnetic Tracking System for Heart Surgery.
Cardiac ablation is a minimally invasive, low risk procedure that can correct heart rhythm problems. Current techniques which determine catheter positioning while a patient is undergoing heart surgery are usually invasive, often inaccurate, and require some forms of imaging. In this study, we develop a unique real-time tracking system which can track the position and orientation of a medical catheter inside a human heart with fast update rate of 200 Hz and high precision of 1.6 mm. The system utilizes a magnetic field-based positioning method involving an efficient solution algorithm, new magnetic field detection hardware and software designs. We show that this type of positioning has the benefits of not needing a line-of-sight between emitter and sensor, supporting a wide dynamic range, and can be applied to other medical systems in need of real-time positioning.


Comparison between tuberculoproteins A and C in the serodiagnosis of tuberculosis by enzyme-linked immunosorbent assay.
Tuberculoproteins A and C obtained from culture filtrate of Mycobacterium tuberculosis by alcohol fractionation were utilized in an enzyme-linked immunosorbent assay to measure the amount of reactive IgG in the sera from advanced and moderately advanced tuberculosis patients, leprosy patients and normal individuals. The A-protein detected significant levels of IgG in the sera from both advanced and moderately-advanced tuberculosis patients and patients with leprosy as compared to the normal group. Employing the C-protein, only sera from the advanced tuberculosis patients group gave significantly positive results when compared with the normal control group. The data show that the A-protein is more potent than the C-protein and has a potential serodiagnostic value.


Ras Signaling Inhibitors Attenuate Disease in Adjuvant-Induced Arthritis via Targeting Pathogenic Antigen-Specific Th17-Type Cells.
The Ras family of GTPases plays an important role in signaling nodes downstream to T cell receptor and CD28 activation, potentially lowering the threshold for T-cell receptor activation by autoantigens. Somatic mutation in NRAS or KRAS may cause a rare autoimmune disorder coupled with abnormal expansion of lymphocytes. T cells from rheumatoid arthritis (RA) patients show excessive activation of Ras/MEK/ERK pathway. The small molecule farnesylthiosalicylic acid (FTS) interferes with the interaction between Ras GTPases and their prenyl-binding chaperones to inhibit proper plasma membrane localization. In the present study, we tested the therapeutic and immunomodulatory effects of FTS and its derivative 5-fluoro-FTS (F-FTS) in the rat adjuvant-induced arthritis model (AIA). We show that AIA severity was significantly reduced by oral FTS and F-FTS treatment compared to vehicle control treatment. FTS was as effective as the mainstay anti-rheumatic drug methotrexate, and combining the two drugs significantly increased efficacy compared to each drug alone. We also discovered that FTS therapy inhibited both the CFA-driven in vivo induction of Th17 and IL-17/IFN-γ producing "double positive" as well as the upregulation of serum levels of the Th17-associated cytokines IL-17A and IL-22. By gene microarray analysis of effector CD4+ T cells from CFA-immunized rats, re-stimulated in vitro with the mycobacterium tuberculosis heat-shock protein 65 (Bhsp65), we determined that FTS abrogated the Bhsp65-induced transcription of a large list of genes (e.g., Il17a/f, Il22, Ifng, Csf2, Lta, and Il1a). The functional enrichment bioinformatics analysis showed significant overlap with predefined gene sets related to inflammation, immune system processes and autoimmunity. In conclusion, FTS and F-FTS display broad immunomodulatory effects in AIA with inhibition of the Th17-type response to a dominant arthritogenic antigen. Hence, targeting Ras signal-transduction cascade is a potential novel therapeutic approach for RA.


Combined somatic and psychiatric care--effects on personnel treating drug addicts with infectious diseases.
Infectious disease care, psychiatric care of drug addicts, and social care were combined in a ward for drug addicts with infectious diseases. The aim of this study was to evaluate the effects on the personnel (n = 22). One ward with infectious disease care of HIV and AIDS patients (n = 24) and another with nonsomatic care of drug addicts (n = 18) were selected to make comparisons possible. The questionnaire concerned psychosocial work environment and health. The personnel at the new ward also participated in a semistructured interview. The personnel at the special ward experienced a significantly higher degree of emotional exhaustion and lack of ability to concentrate than the comparison groups. They also reported a higher degree of lack of clarity, more job strain, and more difficulties due to demands from patients. The combined care is probably associated with heavier psychological burdens than other forms of care. In spite of this, the personnel experienced their work as meaningful and mentally stimulating.


Fluorescence-On Imaging of Reticulophagy Enabled by an Acidity-Reporting Solvatochromic Probe.
Aberrant autophagy of the endoplasmic reticulum (reticulophagy) is engaged in diverse pathological disorders. Herein, we reported sensitive imaging of reticulophagy with ER-Green-proRed, a diad combining a solvatochromic entity of trifluoromethylated naphthalimide for long-term ER tracking by green fluorescence and an entity of rhodamine-lactam fluorogenic to lysosomal acidity. Stringently accumulated in the ER to give green fluorescence, ER-Green-proRed exhibits robust red fluorescence upon codelivery with the ER subdomain into lysosomes. The relevance of turn-on red fluorescence to reticulophagy was validated by reticulophagy modulated by starvation, reticulophagic receptors, and autophagy inhibition. This imaging method was successfully employed to discern reticulophagy induced by various pharmacological agents. These results show the potential of ER-targeted pH probes, as exemplified by ER-Green-proRed, to image reticulophagy and to identify reticulophagy inducers.


Radiofrequency denervation for chronic low back pain.
Radiofrequency (RF) denervation, an invasive treatment for chronic low back pain (CLBP), is used most often for pain suspected to arise from facet joints, sacroiliac (SI) joints or discs. Many (uncontrolled) studies have shown substantial variation in its use between countries and continued uncertainty regarding its effectiveness. The objective of this review is to assess the effectiveness of RF denervation procedures for the treatment of patients with CLBP. The current review is an update of the review conducted in 2003. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, three other databases, two clinical trials registries and the reference lists of included studies from inception to May 2014 for randomised controlled trials (RCTs) fulfilling the inclusion criteria. We updated this search in June 2015, but we have not yet incorporated these results. We included RCTs of RF denervation for patients with CLBP who had a positive response to a diagnostic block or discography. We applied no language or date restrictions. Pairs of review authors independently selected RCTs, extracted data and assessed risk of bias (RoB) and clinical relevance using standardised forms. We performed meta-analyses with clinically homogeneous studies and assessed the quality of evidence for each outcome using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach. In total, we included 23 RCTs (N = 1309), 13 of which (56%) had low RoB. We included both men and women with a mean age of 50.6 years. We assessed the overall quality of the evidence as very low to moderate. Twelve studies examined suspected facet joint pain, five studies disc pain, two studies SI joint pain, two studies radicular CLBP, one study suspected radiating low back pain and one study CLBP with or without suspected radiation. Overall, moderate evidence suggests that facet joint RF denervation has a greater effect on pain compared with placebo over the short term (mean difference (MD) -1.47, 95% confidence interval (CI) -2.28 to -0.67). Low-quality evidence indicates that facet joint RF denervation is more effective than placebo for function over the short term (MD -5.53, 95% CI -8.66 to -2.40) and over the long term (MD -3.70, 95% CI -6.94 to -0.47). Evidence of very low to low quality shows that facet joint RF denervation is more effective for pain than steroid injections over the short (MD -2.23, 95% CI -2.38 to -2.08), intermediate (MD -2.13, 95% CI -3.45 to -0.81), and long term (MD -2.65, 95% CI -3.43 to -1.88). RF denervation used for disc pain produces conflicting results, with no effects for RF denervation compared with placebo over the short and intermediate term, and small effects for RF denervation over the long term for pain relief (MD -1.63, 95% CI -2.58 to -0.68) and improved function (MD -6.75, 95% CI -13.42 to -0.09). Lack of evidence of short-term effectiveness undermines the clinical plausibility of intermediate-term or long-term effectiveness. When RF denervation is used for SI joint pain, low-quality evidence reveals no differences from placebo in effects on pain (MD -2.12, 95% CI -5.45 to 1.21) and function (MD -14.06, 95% CI -30.42 to 2.30) over the short term, and one study shows a small effect on both pain and function over the intermediate term. RF denervation is an invasive procedure that can cause a variety of complications. The quality and size of original studies were inadequate to permit assessment of how often complications occur. The review authors found no high-quality evidence suggesting that RF denervation provides pain relief for patients with CLBP. Similarly, we identified no convincing evidence to show that this treatment improves function. Overall, the current evidence for RF denervation for CLBP is very low to moderate in quality; high-quality evidence is lacking. High-quality RCTs with larger patient samples are needed, as are data on long-term effects.


Context-dependent effects of proline residues on the stability and folding pathway of ubiquitin.
Substitution of trans-proline at three positions in ubiquitin (residues 19, 37 and 38) produces significant context-dependent effects on protein stability (both stabilizing and destabilizing) that reflect changes to a combination of parameters including backbone flexibility, hydrophobic interactions, solvent accessibility to polar groups and intrinsic backbone conformational preferences. Kinetic analysis of the wild-type yeast protein reveals a predominant fast-folding phase which conforms to an apparent two-state folding model. Temperature-dependent studies of the refolding rate reveal thermodynamic details of the nature of the transition state for folding consistent with hydrophobic collapse providing the overall driving force. Brønsted analysis of the refolding and unfolding rates of a family of mutants with a variety of side chain substitutions for P37 and P38 reveals that the two prolines, which are located in a surface loop adjacent to the C terminus of the main alpha-helix (residues 24-33), are not significantly structured in the transition state for folding and appear to be consolidated into the native structure only late in the folding process. We draw a similar conclusion regarding position 19 in the loop connecting the N-terminal beta-hairpin to the main alpha-helix. The proline residues of ubiquitin are passive spectators in the folding process, but influence protein stability in a variety of ways.


Pattern of high voltage electrical injuries in the Kashmir valley: a 10-year single centre experience.
The objective was to study the clinical profile of high voltage electrical injuries in Kashmir, and various prevention and safety measures to bring down the incidence of such injuries in the future. All patients (176) with high voltage electrical injuries reporting to our centre from January 2001 to December 2010 were included in the study. The most common age group was 20-40 years, with mean age of 29.77 ± 8.98 years. Incidence was higher among the rural population (68.75%) than in urban areas (31.25%), and in the winter months. Electricians comprised 47.16% of victims. The most common mode of injury was touching a live wire directly or indirectly, and was seen in 63.64% of victims. Average total body surface burned was 15.27 ± 10.15 percent. Right upper limb was most commonly involved (64.20% of patients). Compartment syndrome was seen in 40.34% of patients, and fasciotomies on all the affected limbs saved around half of them. An average of 3.91 surgical procedures per patient were performed. Around one-third of the victims required major amputations. Reconstructive procedures were required in 49.43% of patients. Average hospital stay was 26.81 days. Average mortality rate was 2.27%. High voltage electrical injuries are not uncommon in the Kashmir Valley, and electrical workers are at higher risk. The incidence of high voltage injuries would not be so high if the workers were properly trained, hazards of high-tension lines were explained and the use of safety equipment was made mandatory.


Recurrent disc prolapse as a cause of recurrent pain after laminectomy for lumbar disc lesions.
Recurrent disc lesions occur in about 19 percent of patients having a primary laminectomy and occurring in just under half (46 percent) of those suffering recurrent pain. The clinical features are similar to those of a primary disc lesion. The most likely site (two out of three) is the same disc level as before, with an equal probability of involving the previous or its opposite side. Re-operation appears to carry a good prognosis, with 80 percent good results, while with conservative treatment 45 percent will settle down in less than three months.


Reactions of the diiron enzyme stearoyl-acyl carrier protein desaturase.
Stearoyl-acyl carrier protein Delta(9) desaturase (Delta9D) produces oleic acid, a nutritionally valuable fatty acid containing a cis double bond between C-9 and C-10. This multiprotein diiron enzyme complex reacts with stearoyl-acyl carrier protein, reduced [2Fe-2S] ferredoxin, and O(2) to complete the highly regiospecific and stereoselective desaturation reaction. Interactions with the acyl chain provide stability to the enzyme-substrate complex, give an energetic contribution to catalytic selectivity, and help to order the electron transfer, O(2) binding, and C-H bond cleavage steps of catalysis. Reactions with natural acyl chains indicate the involvement of a highly reactive diiron intermediate capable of oxidizing secondary C-H bonds (bond dissociation energy approximately 95 kcal/mol), but also capable of diagnostic O-atom transfer reactions with the appropriate substrate analogues. For soluble Delta9D, the natural reaction may initiate at the C-10 position, in contrast to the well-established initial reactivity of the membrane enzyme homologue stearoyl-coenzyme A (CoA) Delta(9) desaturase at the C-9 position.


Effects of subacute treatment with toluene on cerebrocortical alpha- and beta-adrenergic receptors in the rat. Evidence for an increased number and a reduced affinity of beta-adrenergic receptors.
Subacute treatment with toluene (80-1500 p.p.m.) produces a dose-dependent reduction of affinity and increase in density of the beta-adrenergic antagonist [3H]dihydroalprenolol binding sites in the frontoparietal cortex of the male rat, while the binding characteristics of alpha 1-adrenergic ([3H]WB 4101) and alpha 2-adrenergic ([3H]p-aminoclonidine) binding sites in the same region is unaffected by this treatment as evaluated in vitro. Therefore, it is suggested that the cortical beta-adrenergic receptors are particularly vulnerable to the action of toluene in vivo. It is speculated that as a result cortical beta-adrenergic neurotransmission may be altered following exposure to low concentrations of toluene, possibly related to the physico-chemical properties of toluene, leading to changes in membrane fluidity.


Combined method of free lateral leg perforator flap with cervicoplasty for reconstruction of anterior cervical scar contractures: a new flap.
Anterior cervical scar contracture remains a challenging problem for the plastic surgeon. Recent advances in flap techniques have made it possible to transfer various kinds of autogenous tissue. A free lateral leg perforator flap (LLPF) was first introduced and developed to reconstruct this burn deformity, according to the special nature of perforator anatomy. The authors used this flap to resurface post-burn anterior cervical contracture in a 31-year-old female patient with second-to-third-degree flame burns. The size of the excised scar was 25 x 5.5 cm; the size of the flap was 22 x 8 cm, with total flap survival. The hospital stay was 9 days, and the donor site was covered with a split-thickness skin graft. After a 5-month follow-up, functional improvement was evaluated by an increase in extension of 33 degrees (preoperative 92 to postoperative 125 degrees); an increase in rotation of 15 degrees (preoperative 70 to postoperative 85 degrees); and an increase in lateral flexion of 10 degrees (preoperative 35 to postoperative 45 degrees). The cervicomandibular angle was improved by 20 degrees (preoperative 110 degrees to postoperative 90 degrees). Both functional and aesthetic results, including contour restoration, can be achieved, using this kind of perforator flap combined with cervicoplasty.


UCSC genome browser: deep support for molecular biomedical research.
The volume and complexity of genomic sequence data, and the additional experimental data required for annotation of the genomic context, pose a major challenge for display and access for biomedical researchers. Genome browsers organize this data and make it available in various ways to extract useful information to advance research projects. The UCSC Genome Browser is one of these resources. The official sequence data for a given species forms the framework to display many other types of data such as expression, variation, cross-species comparisons, and more. Visual representations of the data are available for exploration. Data can be queried with sequences. Complex database queries are also easily achieved with the Table Browser interface. Associated tools permit additional query types or access to additional data sources such as images of in situ localizations. Support for solving researcher's issues is provided with active discussion mailing lists and by providing updated training materials. The UCSC Genome Browser provides a source of deep support for a wide range of biomedical molecular research (http://genome.ucsc.edu).


Complex Regional Pain Syndrome: A Comprehensive Qualitative Research Study on Unmet Needs in the "Patient Journey".
This qualitative research study aimed to characterize the "patient journey" for patients with complex regional pain syndrome (CRPS) and identify the unmet needs related to the management and treatment of the condition for healthcare providers (HCPs), patients, and their caregivers. Multifaceted, dynamic methodology, iteratively gathering cognitive, emotional and social insights, was used to support and conduct in-depth, immersion interviews across the USA with 59 HCPs in-office and in roundtable discussions, and 20 patient-support partner dyads in-home. Patients were aged >18 years, primarily female, and all were diagnosed with CRPS (limited to type 1 in this patient cohort). Results show that the current state of CRPS treatment may fall short in multiple key areas. In some cases, poor awareness of CRPS causes delayed diagnoses impacting the opportunity for early treatment, resulting in long-term poor health outcomes. Consequently, the CRPS "patient journey" may be characterized by clinical frustration of physicians and disappointment for some patients. The poor treatment experiences and outcomes for some patients and HCPs may build the perception of a non-collaborative relationship. HCPs and patients agree that an effective treatment would be one that addresses CRPS rather than its symptoms, and the availability of such an option would transform the treatment experience. CRPS leads to cognitive, social and emotional burdens for patients and their caregivers. There is an unmet need for improved CRPS disease awareness and successful therapeutic options to aid in earlier diagnoses, effective treatment and better outcomes for HCPs, patients, and their caregivers.


The efficacy and safety of condoliase for lumbar disc herniation: a systematic review and meta-analysis.
Background: Chemonucleolysis is a minimally invasive treatment of lumbar disc herniation (LDH). However, the low specificity of the enzyme and the existence of serious adverse events limit the application of chemonucleolysis. Clinical studies in recent years have shown that Chondroitin sulfate ABC endolyase (condoliase) is a potential therapeutic enzyme for LDH. Aim. A meta-analysis was conducted to determine the efficacy and safety of condoliase in LDH treatment. Methods: We searched Web of Science, Embase, PubMed, and Cochrane Library databases. Two reviewers independently screened articles, extracted data, and assessed the risk of bias. The outcomes were the total effective rate, Oswestry Disability Index (ODI) score change, the proportion of lumbar surgery after condoliase treatment, herniated mass volume change, Pfirrmann grade change, and adverse events. Review Manager 5.3 and Stata 12.0 were used for meta-, sensitivity, and bias analysis. Results: Ten studies were included. A single-arm meta-analysis showed that the total effective rate was 78% [95% confidence interval (CI) 75%-81%], the proportion of surgery was 9% (95% CI 7%-12%), the proportion of Pfirrmann grade change was 43% (95%CI 38%-47%), and the adverse events were 4% (95% CI 2%-6%) after condoliase treatment. The two-arm meta-analysis showed that the ODI score change [standardized mean difference (SMD) -2.46, 95% CI -3.30 to -1.63] and the herniated mass volume change (SMD -16.97, 95% CI -23.92 to -10.03) of the condoliase treatment group were greater than those of the placebo control group, and there was no difference in adverse events between the two groups (OR 1.52, 95% CI 0.60-3.85). The results of sensitivity and publication bias analyses showed that the results were robust. Conclusion: Condoliase intradiscal injection has excellent eutherapeutic and safety for LDH, thus, has considerable potential as a treatment option besides conservative treatment and surgical intervention for LDH. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022375492, PROSPERO (CRD42022375492).


In Human Visualization of Ibrutinib-Induced CLL Compartment Shift.
Bruton tyrosine kinase inhibitor ibrutinib is effective in treating chronic lymphocytic leukemia (CLL). However, after ibrutinib treatment initiation, patients frequently experience an increase of CLL blood cell count. This phenomenon in clinical practice is thought to reflect a "compartment shift" of CLL cells from lymph nodes to the peripheral blood, but the actual shifting has not yet been demonstrated. Using [68Ga]Pentixafor-PET/MRI for in vivo CXCR4 visualization, we here provide images of topical changes of CLL cells upon ibrutinib treatment. Within the first month of ibrutinib treatment, mean standardized [68Ga]Pentixafor uptake decreased in the bone marrow and lymph nodes, whereas [68Ga]Pentixafor uptake increased in the spleen. Leukocytosis rose, as did numbers of CXCR4high (tissue-resident) CLL cells. Volumes of lymph nodes and spleen decreased. Upon longer ibrutinib treatment, leukocytosis decreased, followed by a decrease of [68Ga]Pentixafor uptake in the spleen. These results support the preexisting clinical hypothesis of a "compartment shift" of CLL cells from the lymph nodes to the peripheral blood, but also refine the mechanistic model by describing early clearing of the bone marrow and redistribution of CLL cells to the orthotopic splenic cavernous system in response to ibrutinib treatment.


Stroke in Ehlers-Danlos Syndrome Kyphoscoliotic Type: Dissection or Vasculitis?
Patients with the kyphoscoliotic type of Ehlers-Danlos syndrome have an increased risk of vascular complications such as aortic dissection and perforation. Cerebral ischemia has only rarely been documented. This 13-year-old girl with the kyphoscoliotic type of Ehlers-Danlos syndrome experienced a large right middle cerebral artery distribution infarction. Full intravenous heparinization was started in response to presumed arterial dissection. Magnetic resonance imaging studies including magnetic resonance angiography and digital subtraction angiography, however, did not confirm dissection but suggested with cerebral vasculitis extending from the intradural right internal carotid artery to the M2 branches of the middle cerebral artery. Combined steroid and cyclophosphamide therapy was associated with clinical improvement. Two months later she died from hemorrhagic shock caused by a two-sided spontaneous rupture of the aortic artery. Cerebral vasculitis should be included in the differential diagnosis of vascular complications in kyphoscoliotic type of Ehlers-Danlos syndrome.


Usefulness of Two Independent DNA and RNA Tissue-Based Multiplex Assays for the Routine Care of Advanced NSCLC Patients.
Personalized medicine is nowadays a paradigm in lung cancer management, offering important benefits to patients. This study aimed to test the feasibility and utility of embedding two multiplexed genomic platforms as the routine workup of advanced non-squamous non-small cell lung cancer (NSCLC) patients. Two parallel multiplexed approaches were performed based on DNA sequencing and direct digital detection of RNA with nCounter® technology to evaluate gene mutations and fusions. The results were used to guide genotype-directed therapies and patient outcomes were collected. A total of 224 advanced non-squamous NSCLC patients were prospectively included in the study. Overall, 85% of samples were successfully characterized at DNA and RNA levels and oncogenic drivers were found in 68% of patients, with KRAS, EGFR, METΔex14, BRAF, and ALK being the most frequent (31%, 19%, 5%, 4%, and 4%, respectively). Among all patients with complete genotyping results and follow-up data (n = 156), the median overall survival (OS) was 1.90 years (confidence interval (CI) 95% 1.69-2.10) for individuals harbouring an actionable driver treated with a matched therapy, compared with 0.59 years (CI 95% 0.39-0.79) in those not eligible for any targeted therapy and 0.61 years (CI 95% 0.12-1.10) in patients with no drivers identified (p < 0.001). Integrating DNA and RNA multiplexing technologies into the routine molecular testing of advanced NSCLC patients is feasible and useful and highlights the necessity of widespread integrating comprehensive molecular diagnosis into lung cancer care.


Negotiating between individual and joint goals in ensemble musical performance.
Successful joint action requires negotiation, especially in the event of goal incongruence. This article addresses goal incongruence in joint musical performance by manipulating the congruence of score instructions (congruent/incongruent) regarding tempo (speed) and dynamics (sound intensity) given to piano duos. The aim is to investigate how co-performers negotiate incongruent instructions for tempo and dynamics by balancing the prioritisation of individual goals versus the joint outcome and how this negotiation is modulated by musical expertise and personality (locus of control). In total, 14 pairs of pianists, who were not informed of the congruence manipulation, were placed back-to-back and were directed to achieve a successful performance over four repeated performances without verbal communication. Interpersonal coordination generally improved from the first to final performance in the congruent and incongruent conditions for both the tempo and dynamics tasks. Furthermore, in incongruent conditions, results suggest that performers prioritise the joint performance in the tempo task, but prioritise their own performance in the dynamics task. Although individual performance appears to be modulated by musical expertise, the balance of individual/joint performance across the duo is not influenced by musical part (melody vs accompaniment), expressive instruction, musical expertise or locus of control.


ABCA1 overexpression worsens colorectal cancer prognosis by facilitating tumour growth and caveolin-1-dependent invasiveness, and these effects can be ameliorated using the BET inhibitor apabetalone.
At the time of diagnosis, 20% of patients with colorectal cancer present metastasis. Among individuals with primary lesions, 50% of them will develop distant tumours with time. Therefore, early diagnosis and prediction of aggressiveness is crucial for therapy design and disease prognosis. Tumoral cells must undergo significant changes in energy metabolism to meet increased structural and energetic demands for cell proliferation, and metabolic alterations are considered to be a hallmark of cancer. Here, we present the ATP-binding cassette transporter (ABCA1), a regulator of cholesterol transport, as a new marker for invasion and colorectal cancer survival. ABCA1 is significantly overexpressed in patients at advanced stages of colorectal cancer, and its overexpression confers proliferative advantages together with caveolin-1 dependent-increased migratory and invasive capacities. Thus, intracellular cholesterol imbalances mediated by ABCA1 overexpression may contribute to primary tumour growth and dissemination to distant locations. Furthermore, we demonstrate here that increased levels of apolipoprotein A1 (APOA1), a protein involved in cholesterol efflux and high-density lipoprotein constitution, in the extracellular compartment modulates expression of ABCA1 by regulating COX-2, and compensate for ABCA1-dependent excessive export of cholesterol. APOA1 emerges as a new therapeutic option to inhibit the promotion of colorectal cancer to metastasis by modulating intracellular cholesterol metabolism. Furthermore, we propose apabetalone, an orally available small molecule that is currently being evaluated in clinical trials for the treatment of atherosclerosis, as a new putative therapeutic option to prevent colorectal cancer progression by increasing APOA1 expression and regulating reverse transport of cholesterol.


[Age and sexuality from the viewpoint of the inmates of homes for the aged and nursing homes].
This work refers to the former informations. It expands the hitherto existing way of investigation by the use of unifactoral , univariate and multifactoral , univariate models of factor efficacy. The medium coinage of all indicators of the investigated need lets percept significant differences in the groups of age, sex, personal status, time of being in homes and content of work. So, young groups of age expect from the new partner a greater readiness for intimate contacts. Female home inhabitants are sensitive for emotional relations between each other, male inhabitants are stronger interested in sexual aspects. The importance of these relations is increasing by higher content of work. The application of multifactoral , univariate models divides the settled efficacy of the elected characteristics for the person of inhabitant into main and interaction effects. The results let percept deep relations of factor efficacy between these characteristics at elected indicators of the central questions. At the end there is given a summed view of the results of all three articles.


Comparison between Surgical Outcomes of LASIK with and without Laser Asymmetric Keratectomy to Avoid Conventional Laser Refractive Surgery Adverse Effects.
This study compared one-year postoperative outcomes of laser refractive surgery combined with laser asymmetric keratectomy (LAK) and laser in situ keratomileusis (LASIK)for myopia correction in middle-aged patients (aged 40-49 years) with a total corneal thickness deviation (summed across four directions) ≥ 80 microns. The control group (n = 26; 52 eyes) underwent LASIK; the comparison group (n = 26; 52 eyes) underwent combined laser refractive surgery and LAK. Age, spherical equivalence, uncorrected visual acuity (near and far), corneal irregularity on the Orbscan map, sum of corneal thickness deviations in four directions, corneal thickness distribution, distance between the maximum posterior elevation (best-fit sphere; BFS) and visual axis, and postoperative blurring scores were analysed retrospectively between the groups. Both groups had similar preoperative findings. Postoperatively, the sum of corneal thickness deviations in four directions (p = 0.000), distance between maximum posterior elevation (BFS) and visual axis (p = 0.003),blurring score (p = 0.001), and corneal irregularity in the 3.0 and 5.0 mm zones on the Orbscan map (p = 0.033 and p < 0.0001, respectively) were significantly lower in the comparison group (p = 0.000). LAK reduced total corneal thickness deviation, improved corneal symmetry, and reduced blurring scores significantly, one-year postoperatively. LAK could resolve shortcomings of LASIK, producing better surgical outcomes.


The salmon louse genome: Copepod features and parasitic adaptations.
Copepods encompass numerous ecological roles including parasites, detrivores and phytoplankton grazers. Nonetheless, copepod genome assemblies remain scarce. Lepeophtheirus salmonis is an economically and ecologically important ectoparasitic copepod found on salmonid fish. We present the 695.4 Mbp L. salmonis genome assembly containing ≈60% repetitive regions and 13,081 annotated protein-coding genes. The genome comprises 14 autosomes and a ZZ-ZW sex chromosome system. Assembly assessment identified 92.4% of the expected arthropod genes. Transcriptomics supported annotation and indicated a marked shift in gene expression after host attachment, including apparent downregulation of genes related to circadian rhythm coinciding with abandoning diurnal migration. The genome shows evolutionary signatures including loss of genes needed for peroxisome biogenesis, presence of numerous FNII domains, and an incomplete heme homeostasis pathway suggesting heme proteins to be obtained from the host. Despite repeated development of resistance against chemical treatments L. salmonis exhibits low numbers of many genes involved in detoxification.


Efficacy of oritavancin in a murine model of Bacillus anthracis spore inhalation anthrax.
The inhaled form of Bacillus anthracis infection may be fatal to humans. The current standard of care for inhalational anthrax postexposure prophylaxis is ciprofloxacin therapy twice daily for 60 days. The potent in vitro activity of oritavancin, a semisynthetic lipoglycopeptide, against B. anthracis (MIC against Ames strain, 0.015 microg/ml) prompted us to test its efficacy in a mouse aerosol-anthrax model. In postexposure prophylaxis dose-ranging studies, a single intravenous (i.v.) dose of oritavancin of 5, 15, or 50 mg/kg 24 h after a challenge with 50 to 75 times the median lethal dose of Ames strain spores provided 40, 70, and 100% proportional survival, respectively, at 30 days postchallenge. Untreated animals died within 4 days of challenge, whereas 90% of control animals receiving ciprofloxacin at 30 mg/kg intraperitoneally twice daily for 14 days starting 24 h after challenge survived. Oritavancin demonstrated significant activity post symptom development; a single i.v. dose of 50 mg/kg administered 42 h after challenge provided 56% proportional survival at 30 days. In a preexposure prophylaxis study, a single i.v. oritavancin dose of 50 mg/kg administered 1, 7, 14, or 28 days before lethal challenge protected 90, 100, 100, and 20% of mice at 30 days; mice treated with ciprofloxacin 24 h or 24 and 12 h before challenge all died within 5 days. Efficacy in pre- and postexposure models of inhalation anthrax, together with a demonstrated low propensity to engender resistance, promotes further study of oritavancin pharmacokinetics and efficacy in nonhuman primate models.


Mn2+-Assisted DNA Oligonucleotide Adsorption on Ti2C MXene Nanosheets.
As a new type of 2D nanomaterial, MXene (transition metal carbide/nitride) nanosheets are already widely used in catalysis, sensing, and energy research. DNA is a popular sensing molecule. Compared to other 2D materials such as graphene oxide, MoS2, and WS2, few fundamental studies were carried out on DNA adsorption by MXene. Due to its exfoliation and delamination process, the surface of MXene is abundant in -F, -OH, and -O- groups, rendering the surface negatively charged and repelling DNA. In previous studies, surface modification of MXene was performed to promote DNA adsorption. Herein, Mn2+ was discovered to promote DNA adsorption on unmodified Ti2C MXene. Different from Ca2+ and Mg2+, Mn2+ can inverse the ζ-potential of the Ti2C MXene to positive. DNA mainly uses its phosphate backbone for adsorption, while its bases contribute significantly less. In addition, delayed DNA desorption was observed through the addition of inorganic phosphate due to the formation of manganese phosphate to gradually extract Mn2+ from the DNA/MXene complex. Finally, DNA-induced DNA desorption from the Ti2C MXene can hardly distinguish the complementary DNA from a random DNA, which is very different from that for graphene oxide. This difference is likely due to the distinct surface chemistry between the MXene and graphene oxide.


Results publications are inadequately linked to trial registrations: An automated pipeline and evaluation of German university medical centers.
Informed clinical guidance and health policy relies on clinicians, policymakers, and guideline developers finding comprehensive clinical evidence and linking registrations and publications of the same clinical trial. To support the finding and linking of trial evidence, the World Health Organization, the International Committee of Medical Journal Editors, and the Consolidated Standards of Reporting Trials ask researchers to provide the trial registration number in their publication and a reference to the publication in the registration. This practice costs researchers minimal effort and makes evidence synthesis more thorough and efficient. Nevertheless, trial evidence appears inadequately linked, and the extent of trial links in Germany remains unquantified. This cross-sectional study aims to evaluate links between registrations and publications across clinical trials conducted by German university medical centers and registered in ClinicalTrials.gov or the German Clinical Trials Registry. Secondary aims are to develop an automated pipeline that can be applied to other cohorts of trial registrations and publications, and to provide stakeholders, from trialists to registries, with guidance to improve trial links. We used automated strategies to download and extract data from trial registries, PubMed, and results publications for a cohort of registered, published trials conducted across German university medical centers and completed between 2009 and 2017. We implemented regular expressions to detect and classify publication identifiers in registrations, and trial registration numbers in publication metadata, abstracts, and full-texts. In breach of long-standing guidelines, 75% (1,418) of trials failed to reference trial registration numbers in both the abstract and full-text of the journal article in which the results were published. Furthermore, 50% (946) of trial registrations did not contain links to their results publications. Seventeen percent (327) of trials had no links, so that associating registration and publication required manual searching and screening. Overall, trials in ClinicalTrials.gov were better linked than those in the German Clinical Trials Registry; PubMed and registry infrastructures appear to drive this difference. Trial registration numbers were more likely to be transferred to PubMed metadata from abstracts for ClinicalTrials.gov trials than for German Clinical Trials Registry trials. Most (78%, 662/849) ClinicalTrials.gov registrations with a publication link were automatically indexed from PubMed metadata, which is not possible in the German Clinical Trials Registry. German university medical centers have not comprehensively linked trial registrations and publications, despite established recommendations. This shortcoming threatens the quality of evidence synthesis and medical practice, and burdens researchers with manually searching and linking trial data. Researchers could easily improve this by copy-and-pasting references between their trial registrations and publications. Other stakeholders could build on this practice, for example, PubMed could capture additional trial registration numbers using automated strategies (like those developed in this study), and the German Clinical Trials Registry could automatically index publications from PubMed.


Activity of vitamin D receptor agonists against dengue virus.
Infections with the mosquito-transmitted dengue virus (DENV) are a pressing public health problem in many parts of the world. The recently released commercial vaccine for DENV has encountered some problems, and there is still no effective drug to treat infections. Vitamin D has a well characterized role in calcium and phosphorus homeostasis, but additionally has a role in the immune response to bacterial and viral pathogens. In this study a number of fused bicyclic derivatives of 1H-pyrrolo[1,2]imidazol-1-one with vitamin D receptor (VDR) agonist activity were evaluated for possible anti-DENV activity. The results showed that five of the compounds were able to significantly inhibit DENV infection. The most effective compound, ZD-3, had an EC50 value of 7.47 μM and a selective index of 52.75. The compounds were only effective when used as a post-infection treatment and treatment significantly reduced levels of infection, virus output, DENV protein expression and genome copy number. These results suggest that these VDR agonists have the potential for future development as effective anti-DENV agents.


Study on the spatial correlation effects and influencing factors of carbon emissions from the electricity industry: a fresh evidence from China.
Carbon emissions from the electricity industry (CEEI) account for a large proportion of China's total carbon emissions, and it is important to study the spatial correlation between CEEI and the influencing factors to promote cross-regional synergistic emission reduction and low-carbon development of the power system. In this paper, the quasi-input-output (QIO) model is applied to assess the transfer of carbon emissions generated by electricity trading based on the consideration of electricity carbon transfer, and the exploratory spatial data analysis (ESDA) method is applied to analyze the spatial correlation effect of carbon emissions from China's electric power sector from 2001 to 2020, analyzes its distribution pattern in both spatial and temporal dimensions, and applies the improved logarithmic mean Divisia index (LMDI) two-stage decomposition model to decompose the changes in CEEI into 11 influencing factors from the perspective of the whole industrial chain of power production, transmission, trade, and consumption. The research results show that (1) the spatial distribution of CEEI has obvious unevenness and aggregation characteristics, with high-high aggregation areas and hot spot aggregation areas generally concentrated in the North China Power Grid and the East China Power Grid, but the aggregation trend is gradually decreasing, while low-low aggregation areas and cold spot aggregation areas are concentrated in the Northwest China Power Grid and the Central China Power Grid, but the area is very limited. (2) The direction of carbon emission diffusion in China's electricity industry is gradually transitioning from southwest-northeast to northwest-southeast, and the east-west diffusion trend is stronger than the north-south diffusion trend and carbon emissions are gradually shifting to the northwest grid. (3) The total amount of electricity production is the most influential factor in the change of CEEI, driving the cumulative growth of CEEI by 4495.34 Mt, followed by GDP per capita and electricity consumption intensity. Coal consumption for power generation, the share of thermal power, and net electricity exports were the main factors inhibiting the increase in carbon emissions from the power sector, with cumulative contributions of -797.74 Mt, -619.99 Mt, and -47.76 Mt, respectively.


Small-cell lung cancer transformation from EGFR-mutant adenocarcinoma after EGFR-TKIs resistance: A case report.
With the recent advancements in molecular biology research, epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have emerged as excellent therapies for patients with EGFR-mutant cancers. However, these patients inevitably develop cross-acquired resistance to EGFR-TKIs. Transformation to small-cell lung cancer (SCLC) is considered a rare resistance mechanism against EGFR-TKI therapy. Here, we report a case of TKI resistance due to SCLC transformation and demonstrate its mechanisms and clinical features. A 54-year-old Chinese man with a history of smoking for 40 years complained of an intermittent cough in March 2019. Transbronchial lung biopsy was performed on the basal segment of the left lower lobe, which confirmed lung adenocarcinoma. In January 2020, repeat biopsy was performed, and the results of immunohistochemistry (IHC) staining showed TTF-1 (+), CK7 (+), napsin A (+), syn (+), and CD56 (+), with a Ki-67 (+) index 80% of small cell carcinomas. Infiltrating adenocarcinomas and small cell carcinomas were observed. Icotinib (125 mg thrice daily) was administered as a first-line treatment from June 2019. We subsequently administered a chemotherapy regimen consisting of etoposide (180 mg, days 1-3) plus cisplatin (45 mg, days 1-3) every 3 weeks for 1 cycle after recurrence. As the patient could not tolerate further chemotherapy, he continued taking icotinib orally and received whole-brain radiotherapy 10 times to a total dose of 30 Gy after brain metastases. The patient relapsed after successful treatment with icotinib for 9 months. A partial response was achieved after 4 cycles of chemotherapy, and despite the brief success of chemotherapy, our patient exhibited brain metastasis and metastases of the eleventh thoracic spine and the second lumbar vertebra with pathological fracture. The patient eventually died of aggressive cancer progression. Our case highlights the possibility of SCLC transformation from EGFR-mutant adenocarcinoma and the importance of repeat biopsy for drug resistance. Serum neuron-specific enolase levels may also be useful for detecting early SCLC transformation.


Hospital Nurses' Work Activity in a Technology-Rich Environment: A Triangulated Quality Improvement Assessment.
The aim of this project was to describe hospital nurses' work activity through observations, nurses' perceptions of time spent on tasks, and electronic health record time stamps. Nurses' attitudes toward technology and patients' perceptions and satisfaction with nurses' time at the bedside were also examined. Activities most frequently observed included documenting in and reviewing the electronic health record. Nurses' perceptions of time differed significantly from observations, and most patients rated their satisfaction with nursing time as excellent or good.


Treatment of abdominal aortic aneurysms in Korea: a nationwide study.
Although endovascular aneurysm repair (EVAR) has been shown to be superior to open surgical repair (OSR) for abdominal aortic aneurysm (AAA) treatment, no large-scale studies in the Korean population have compared outcomes and costs. The National Health Insurance Service database in Korea was screened to identify AAA patients treated with EVAR or OSR from 2008 to 2019. Perioperative, early postoperative, and long-term survival were compared, as were reinterventions and complications. Patients were followed-up through 2020. Of the 13,631 patients identified, 2,935 underwent OSR and 10,696 underwent EVAR. Perioperative mortality rate was lower in the EVAR group (4.2% vs. 8.0%, P < 0.001) even after excluding patients with ruptured AAA (2.7% vs. 3.3%, P = 0.003). However, long-term mortality rate per 100 person-years was significantly higher in the EVAR than in the OSR group (9.0 vs. 6.4, P < 0.001), and all-cause mortality was lower in the OSR group (hazard ratio, 0.9; 95% confidence interval, 0.87-0.97, P = 0.008). EVAR had a higher AAA-related reintervention rate per 100 person-years (1.75 vs. 0.52), and AAA-related reintervention costs were almost 10-fold higher with EVAR (US dollar [USD] 6,153,463) than with OSR (USD 624,216). While EVAR may have short-term advantages, OSR may provide better long-term outcomes and cost-effectiveness for AAA treatment in the Korean population, under the medical expense system in Korea.


Differential effects of base-pair mismatch on intrachromosomal versus extrachromosomal recombination in mouse cells.
To initially determine the effect that base-pair mismatch has on homologous recombination in mammalian cells, we have studied genetic recombination between thymidine kinase (tk) gene sequences from herpes simplex virus 1 and 2. These tk genes are approximately 81% homologous at the nucleotide level. We observed that, in mouse LTK- cells, intrachromosomal recombination between type 1 and type 2 tk sequences is reduced by a factor of at least 1000 relative to the rate of intrachromosomal recombination between homologous type 1 tk sequences. In sharp contrast, the rate of intermolecular or intramolecular extrachromosomal recombination between the heterologous tk sequences introduced by calcium phosphate or microinjection was reduced only by a factor of 3 to 15 compared with extrachromosomal homologous tk crosses. Our results suggest differences between the mechanisms of extrachromosomal and intrachromosomal recombination in mammalian cells.


Flow cytometry may allow microscope-independent detection of holocentric chromosomes in plants.
Two chromosomal structures, known as monocentric and holocentric chromosomes, have evolved in eukaryotes. Acentric fragments of monocentric chromosomes are unequally distributed to daughter cells and/or lost, while holocentric fragments are inherited normally. In monocentric species, unequal distribution should generate chimeras of cells with different nuclear DNA content. We investigated whether such differences in monocentric species are detectable by flow cytometry (FCM) as (i) a decreased nuclear DNA content and (ii) an increased coefficient of variance (CV) of the G1 peak after gamma radiation-induced fragmentation. We compared 13 monocentric and 9 holocentric plant species. Unexpectedly, monocentrics and holocentrics did not differ with respect to parameters (i) and (ii) in their response to gamma irradiation. However, we found that the proportion of G2 nuclei was highly elevated in monocentrics after irradiation, while holocentrics were negligibly affected. Therefore, we hypothesize that DNA-damaging agents induce cell cycle arrest leading to endopolyploidy only in monocentric and not (or to much lesser extent) in holocentric plants. While current microscope-dependent methods for holocentrism detection are unreliable for small and numerous chromosomes, which are common in holocentrics, FCM can use somatic nuclei. Thus, FCM may be a rapid and reliable method of high-throughput screening for holocentric candidates across plant phylogeny.


[Therapy evaluation in child and adolescent psychiatry: inpatient treatment, day care treatment and home treatment in comparison].
The aim of the present study was to compare inpatient, day hospital and home treatment of 10 child psychiatric disorders as defined in the Multi-axial Classification Scheme. The subjects were 109 patients from two child psychiatric hospitals who fulfilled clearly defined criteria. They comprised about 10 to 15% of the total clinical population of the two hospitals. The patient were assigned at random to the three treatment modalities. Treatment effectiveness was evaluated blind by experienced child psychiatrists not involved in the study. There were no significant differences between the treatment modalities in duration of treatment. Neither were there any significant differences between the treatment modalities with respect to treatment effectiveness, although there were some overall differences between different diagnostic categories. For a small group of carefully selected children day hospital and home treatment can therefore be looked upon as alternatives to inpatient treatment.


An actin homolog of the archaeon Thermoplasma acidophilum that retains the ancient characteristics of eukaryotic actin.
Actin, a central component of the eukaryotic cytoskeleton, plays a crucial role in determining cell shape in addition to several other functions. Recently, the structure of the archaeal actin homolog Ta0583, isolated from the archaeon Thermoplasma acidophilum, which lacks a cell wall, was reported by Roeben et al. (J. Mol. Biol. 358:145-156, 2006). Here we show that Ta0583 assembles into bundles of filaments similar to those formed by eukaryotic actin. Specifically, Ta0583 forms a helix with a filament width of 5.5 nm and an axial repeating unit of 5.5 nm, both of which are comparable to those of eukaryotic actin. Eukaryotic actin shows a greater resemblance to Ta0583 than to bacterial MreB and ParM in terms of polymerization characteristics, such as the requirement for Mg(2+), critical concentration, and repeating unit size. Furthermore, phylogenetic analysis also showed a closer relationship between Ta0583 and eukaryotic actin than between MreB or ParM and actin. However, the low specificity of Ta0583 for nucleotide triphosphates indicates that Ta0583 is more primitive than eukaryotic actin. Taken together, our results suggest that Ta0583 retains the ancient characteristics of eukaryotic actin.


Transitional care management reimbursement to reduce COPD readmission.
Reducing preventable readmissions for COPD is an important national health policy goal. Thus far, Centers for Medicare & Medicaid Services (CMS) policies focused on incentivizing improvements in inpatient quality have had variable success. In its 2013 physician-payment rule, CMS announced new payments that reimburse ambulatory care providers for timely posthospital visits and transitional care management services. CMS hopes that posthospital transitional care and services will substitute for readmission, but the evidence supporting this hypothesis is mixed. In this article, we discuss ways for ambulatory pulmonologists to leverage transitional care management payments to enhance access for their patients with COPD while minimizing the risk of a paradoxic increase in readmission rates.


[Neuromuscular stimulation in conditions of vibrational physical activity for the prevention of osteoporosis].
The review discusses the modern possibilities of non-drug rehabilitation of patients with osteoporosis. Osteopenia (osteoporosis) and osteoporosis-associated bone fractures are a global public health problem, and an intensive search is undergoing for new methods of treatment, prevention, diagnosis and screening of this disease. Innovative technologies for influencing bone remodeling using vibration training seem to be an effective method that allows you to simultaneously positively affect maintaining bone density, increasing muscle strength and improving coordination, especially in elderly patients. The evolution of study of the effects of intense neuromuscular stimulation under accelerated physical exertion, which began with fundamental work on experimental animals, now includes numerous clinical studies. Vibrational physical activity is one of the methods of biomechanical stimulation, which is considered as an innovative method in the field of rehabilitation and physiotherapy. The physiological basis of this effect is intensive neuromuscular stimulation, which causes a reflex reaction of skeletal muscles. This scientific review describes the results of both monotherapy and combined methods of exposure to vibrational stimulation using modern pharmacotherapy. Attention is focused on the positions of importance in the design of the study and the planning of rehabilitation programs of uniformly accelerated training.


[Clinical efficacy of shenfu injection in treating severe sepsis and its effects on serum levels of interleukin-6 and interleukin-10].
To observe the therapeutic efficacy of Shenfu Injection (SFI) on patients with severe sepsis and its effects on serum levels of interleukin-6 (IL-6) and interleukin-10 (IL-10). Sixty-eight patients with severe sepsis were randomly assigned to the SFI group (36 cases, treated by SFI + routine therapy) and the control group (32 cases, treated by routine therapy). The acute physiology and chronic health evaluation II (APACHE II) score and Marshall score were observed before treatment, 3 and 7days after treatment. The therapeutic efficacy was assessed, and the 28th-day mortality rates were compared. The serum levels of IL-6 and IL-10 were determined by enzyme-labeled immunosorbent assay (ELISA) before and after treatment. C-reactive protein (CRP) was determined by immunoturbidimetric assay. There was no significant difference in the APACHE II score, Marshall score, IL-6, IL-10, or CRP between the two groups before treatment (P>0.05). APACHE II score and Marshall score of all patients decreased after treatment, with more obvious decrease shown in the SFI group (P<0.05). The mortality rate in the SFI group and the control group was 25.0% (9/36) and 37.5% (12/32) respectively, with no significant difference shown between the two groups (P>0.05). The serum levels of IL-6 and CRP obviously decreased after 7 days of treatment (P<0.05). But more decrement was shown in the SFI group, showing significant difference when compared with the control group (P<0.05). There was no significant difference in the serum IL-10 level between the two groups before and after treatment (P>0.05). SFI could lower the serum IL-6 level, regulate the equilibrium of proinflammatory factors and anti-inflammatory cytokines in severe sepsis patients, thus playing a role in improving the therapeutic efficacy.


Effects of Interferometric Radar Altimeter Errors on Marine Gravity Field Inversion.
The traditional altimetry satellite, which is based on pulse-limited radar altimeter, only measures ocean surface heights along tracks; hence, leads to poorer accuracy in the east component of the vertical deflections compared to the north component, which in turn limits the final accuracy of the marine gravity field inversion. Wide-swath altimetry using radar interferometry can measure ocean surface heights in two dimensions and, thus, can be used to compute vertical deflections in an arbitrary direction with the same accuracy. This paper aims to investigate the impact of Interferometric Radar Altimeter (InRA) errors on gravity field inversion. The error propagation between gravity anomalies and InRA measurements is analyzed, and formulas of their relationship are given. By giving a group of possible InRA parameters, numerical simulations are conducted to analyze the accuracy of gravity anomaly inversion. The results show that the accuracy of the gravity anomalies is mainly influenced by the phase errors of InRA; and the errors of gravity anomalies have a linear approximation relationship with the phase errors. The results also show that the east component of the vertical deflections has almost the same accuracy as the north component.


Isolation, characterisation and enzymatic activity of Streptomyces sp. and its pH control during fermentation process.
Streptomyces sp. with grey white mycelium was isolated from Kodiyakkarai marine segment of east coastal of India. The isolate produced spiny spores and did not produce any diffusible pigments. Various biochemical tests were carried out to confirm the isolate classification. The amylolytic enzyme activity was estimated using the isolated strain which was confirmed by golden yellowish zone formation after using the Gram's iodine stain. The amount of amylase produced by the isolate was 6.15 U/ml. Higher living cells always produce better enzymes, so that the process parameters especially pH was maintained in fermentation chamber for higher growth and also for large-scale growth. For maintaining the pH a mathematical process model was developed using the data obtained during the process. The addition of Kalman's filter along with proportional-integral-derivative controller gave better stability in pH. By maintaining of pH 7, growth rate was significantly increased from 0.51to 0.59 gm/l on day 5 which are discussed in the results and discussions.


Ever dispense of prescribed allergy medication in children growing up close to traffic: a registry-based birth cohort.
Epidemiologic studies have shown conflicting results regarding the role of traffic pollution in the development of allergic disease. This study investigated the relationship between living close to traffic and ever dispense of prescribed oral antihistamines or nasal anti-allergic medication, among young children. The underlying aim was to investigate if children growing up close to traffic pollution are at higher risk of developing allergy in early childhood. We investigated a birth cohort in southern Sweden, consisting of N = 26 128 children (0-6 years) with health outcome and exposure data. Of these children, N = 7898, had additional covariate information. Traffic intensity and yearly averages of dispersion-modeled concentrations of NOX (100 × 100 m grid) at residential addresses, were linked with registry data on dispensed allergy medication (the Swedish Prescribed Drug Register). Individual level covariate information was obtained from questionnaires distributed to parents at Child Health Care-center visits, eight months after birth. Cox proportional hazards regression was used for the statistical analyses. Living in close proximity to a road with equal to or greater than 8640 cars/day (compared to 0-8639 cars/day), was not associated with higher incidence of ever dispensed oral antihistamine or nasal anti-allergic medication, with or without adjustment for confounders (sex, breastfeeding, parental allergy, parental origin, season, and year of birth). Similar results were found in relation to NOX. Traffic-related exposure was not associated with higher incidence of ever dispensed medication against allergy, in children 0-6 years in southern Sweden. These results indicates that traffic-related exposure may not be a risk factor for early onset allergy in children in southern Sweden. However, children with dispense of prescribed allergy medication may be a selected subgroup, and the results for this group may not be generalizable to all children with allergy.


Posttranscriptional mechanisms controlling diurnal gene expression cycles by body temperature rhythms.
In mammals, body temperature oscillates in a daily fashion around a set point of 36°C-37°C. These fluctuations are controlled by the circadian master clock residing in the brain's suprachiasmatic nucleus and, despite their small amplitudes, contribute to the diurnal expression of genes throughout the organism. By focusing on the mechanisms underlying the temperature-dependent accumulation of the cold-inducible RNA-binding protein CIRBP - a factor involved in the tuning of amplitude and phase in circadian clocks of peripheral tissues - we have recently identified a novel mechanism governing temperature-dependent gene expression. This mechanism involves the differential spicing efficiency of primary RNA transcripts under different temperature conditions and thereby determines the fraction of Cirbp pre-mRNA processed into mature mRNA. A genome-wide transcriptome analysis revealed that this mechanism affects the output of hundreds of genes. Here we discuss our findings and future directions toward the identification of specific factors and parameters governing temperature-sensitive splicing efficacy.


The Impact of Radiologist Screening Mammogram Reading Volume on Performance in the Ontario Breast Screening Program.
Although some studies have shown increasing radiologists' mammography volumes improves performance, there is a lack of evidence specific to digital mammography and breast screening program performance targets. This study evaluates the relationship between digital screening volume and meeting performance targets. This retrospective cohort study included 493 radiologists in the Ontario Breast Screening Program who interpreted 1,762,173 screening mammograms in participants ages 50-90 between 2014 and 2016. Associations between annual screening volume and meeting performance targets for abnormal call rate, positive predictive value (PPV), invasive cancer detection rate (CDR), sensitivity, and specificity were modeled using mixed-effects multivariate logistic regression. Most radiologists read 500-999 (36.7%) or 1,000-1,999 (31.0%) screens annually, and 18.5% read ≥2,000. Radiologists who read ≥2,000 annually were more likely to meet abnormal call rate (OR = 3.85; 95% CI: 1.17-12.61), PPV (OR = 5.36; 95% CI: 2.53-11.34), invasive CDR (OR = 4.14; 95% CI: 1.50-11.46), and specificity (OR = 4.07; 95% CI: 1.89-8.79) targets versus those who read 100-499 screens. Radiologists reading 1,000-1,999 screens annually were more likely to meet PPV (OR = 2.32; 95% CI: 1.22-4.40), invasive CDR (OR = 3.36; 95% CI: 1.49-7.59) and specificity (OR = 2.00; 95% CI: 1.04-3.84) targets versus those who read 100-499 screens. No significant differences were observed for sensitivity. Annual reading volume requirements of 1,000 in Canada are supported as screening volume above 1,000 was strongly associated with achieving performance targets for nearly all measures. Increasing the minimum volume to 2,000 may further reduce the potential limitations of screening due to false positives, leading to improvements in overall breast screening program quality.


Laparoscopic Cholecystectomy after the Learning Curve.
Management of gallbladder disease has changed dramatically since the introduction of laparoscopic cholecystectomy (LC) in 1988. Removal of the gallbladder has always been the 'gold standard'. However, the morbidity associated with the large transrectus incision has caused patients and referring physicians alike to refrain from surgical treatment whenever possible. LC offers the same excellent end results of a standard cholecystectomy, but without the pain and ileus seen with the operation.


[Perivesical abscess secondary to ruptured appendicitis : a case report].
A 38 year-old man was referred to our hospital for high fever and lower abdominal pain. The laboratory data showed his inflammatory state with a few puss cells in the urine analysis. Computed tomography (CT) scan and magnetic resonance imaging (MRI) scan demonstrated perivesical abscess and the cystoscopy on the day just before the operation revealed no abnormal findings in the bladder mucosa. In the operation, under the preoperative diagnosis of pyourachus, the appendix with the tip open was found inside the abscess cavity. Therefore, appendectomy and partial cystecomy were carried out. On the grounds of the pathological findings ; remarkable inflammatory change in the perivesical fatty tissue and slight inflammatory lesions in the subserous layer of the appendix, in addition to the clinical course and the retrospective findings of the preoperative MRI scan : existence of a tubular structure connecting with the abscess cavity, the final diagnosis was made as perivesical abscess secondary to ruptured appendicitis. This case is reported with a brief discussion as to the diagnosis and treatment.


Mitral and tricuspid valve repair in hypereosinophilic syndrome.
Hypereosinophilic syndrome (HES) is a rare systemic condition, defined as a persistently elevated eosinophil count associated with end organ damage and the absence of a primary cause. Cardiac involvement occurs in about 50% of patients with HES. Myocardial infiltration results in endomyocardial fibrosis, valve dysfunction and mural thrombus. The atrioventricular valves are almost always involved, resulting in regurgitation due to leaflet restriction, most commonly affecting the posterior mitral valve leaflet. Surgical management remains challenging in patients with HES with limited data on the choice of valve surgery. We describe the case of a 17-year-old woman with HES complicated by congestive cardiac failure secondary to severe mitral and tricuspid regurgitation. Because of refractory heart failure despite medical therapy, surgical mitral and tricuspid valve repair was performed, and an excellent 24-month outcome was achieved. We believe this is the first report of double valve repair in this rare condition.