Development of 3-D Intramural and Surface Potentials in the LV: Microstructural Basis of Preferential Transmural Conduction.
Extracellular potentials measured on the heart surfaces are used to infer events that originate deep within the heart wall. We have reconstructed intramural potentials in three dimensions for the first time, and compare these with epicardial and endocardial surface potentials and cardiac microstructure. Extracellular potentials from intramural point stimulation were measured from a high density 3-D electrode array in the in vivo pig LV. MR and extended volume imaging were used to register electrode locations and characterize fiber and laminar orientations throughout the recording volume. Measured potentials were compared with predictions of tissue-specific bidomain computer activation models. Positive potentials recorded in the LV wall preceded the depolarization wavefront as it spread in the fiber direction. Transverse to this, passive and active potentials spread preferentially in the laminar direction (anisotropy ratio ∼1.6:1). Epicardial surface potentials reflect initial intramural propagation at the stimulus location, but endocardial potentials do not, particularly adjacent to papillary muscles. Measured 3-D potentials were consistently better captured by computer models that incorporate three distinct conductivities aligned with local microstructural axes, but the preferential spread of potentials in the laminar direction was not fully predicted. This study provides evidence for preferential transmural conduction and raises questions about the extent to which intramural electrical events can be inferred from endocardial potentials.


Spatio-temporal changes in biomass carbon sinks in China's forests from 1977 to 2008.
Forests play a leading role in regional and global carbon (C) cycles. Detailed assessment of the temporal and spatial changes in C sinks/sources of China's forests is critical to the estimation of the national C budget and can help to constitute sustainable forest management policies for climate change. In this study, we explored the spatio-temporal changes in forest biomass C stocks in China between 1977 and 2008, using six periods of the national forest inventory data. According to the definition of the forest inventory, China's forest was categorized into three groups: forest stand, economic forest, and bamboo forest. We estimated forest biomass C stocks for each inventory period by using continuous biomass expansion factor (BEF) method for forest stands, and the mean biomass density method for economic and bamboo forests. As a result, China's forests have accumulated biomass C (i.e., biomass C sink) of 1896 Tg (1 Tg=10(12) g) during the study period, with 1710, 108 and 78 Tg C in forest stands, and economic and bamboo forests, respectively. Annual forest biomass C sink was 70.2 Tg C a(-1), offsetting 7.8% of the contemporary fossil CO2 emissions in the country. The results also showed that planted forests have functioned as a persistent C sink, sequestrating 818 Tg C and accounting for 47.8% of total C sink in forest stands, and that the old-, mid- and young-aged forests have sequestrated 930, 391 and 388 Tg C from 1977 to 2008. Our results suggest that China's forests have a big potential as biomass C sink in the future because of its large area of planted forests with young-aged growth and low C density.


Transforming growth factor-beta and insulin-like signalling pathways in parasitic helminths.
The signal transduction pathways involved in regulating developmental arrest in the free-living nematode, Caenorhabditis elegans, are fairly well characterised. However, much less is known about how these processes may influence the developmental timing and maturation in helminth parasites. Here, we provide an overview of two signalling pathways implicated in the regulation of dauer larva formation in C. elegans, the insulin-like signalling pathway and the transforming growth factor-beta pathway, and explore what is known about these signalling pathways in a variety of parasitic helminths. Understanding the differences about how these pathways are affected by environmental cues in free-living versus parasitic species of helminths may provide insights into novel mechanisms for the control or prevention of helminth-induced disease.


Adverse effects of faculty practice on diagnostic content of residents' outpatient experience.
The outpatient experience of two cohorts of family medicine residents was compared. Those who worked at a site with an existing faculty practice had fewer pregnancy-related patient encounters and proportionately more encounters for acute self-limited care compared with residents at a site without a faculty practice (P less than .001). More important, the faculty-associated residents also cared for fewer patients with a variety of chronic diseases and saw them less frequently. These findings suggest that a coexistent faculty practice may have adverse effects on outpatient training in primary care.


A remarkable reduction in the susceptibility of Neisseria gonorrhoeae isolates to cephems and the selection of antibiotic regimens for the single-dose treatment of gonococcal infection in Japan.
We compared the susceptibilities of 100 Neisseria gonorrhoeae isolates obtained from January to June 2000 to a variety of antimicrobial agents, including various cephems, with the susceptibilities of 55 isolates obtained from May to December 1995. In 11 of the 15 cephems tested, the MIC50 (minimum inhibitory concentration for 50% of isolates) ratios, calculated by dividing the MIC50 for isolates from 2000 by that for isolates from 1995, showed 4-fold to 16-fold differences. The MIC90 ratios of cefodizime and cefditoren showed only a 1-fold and 2-fold difference, respectively. However, the MIC90 ratios of the remaining 13 cephems showed 4-fold to 64-fold differences. We selected the most favorable antibiotic regimens for the single-dose treatment of gonorrhea in Japan according to the antigonococcal activity and pharmacokinetics, based on the criterion (therapeutic time) proposed by Moran and Levine i.e., the regimen should produce a concentration in the serum or plasma at least four times that of the MIC90 value for at least 10 h. Of the 20 single-dose regimens evaluated, only ceftriaxone 1 g intravenously and cefodizime 1 g intravenously were found to have a therapeutic time of more than 10 h for the isolates from 2000. Our results indicated that the susceptibilities of the isolates from 2000 to all the cephems tested, except for cefditoren and cefodizime, decreased remarkably in comparison with the susceptibilities of the isolates from 1995, while parenteral ceftriaxone 1 g and cefodizime 1 g appeared to be the most favorable single-dose regimens for the treatment of gonococcal infections in Japan.


Network-Guided Transcranial Magnetic Stimulation for Depression.
First, we will identify candidate predictive biomarkers of antidepressant response of TMS based on the neuroimaging literature. Next, we will review the effects of TMS on networks involved in depression. Finally, we will discuss ways in which our current understanding of network engagement by TMS may be used to optimize its antidepressant effect. The past few years has seen significant interest in the antidepressant mechanisms of TMS. Studies using functional neuroimaging and neurochemical imaging have demonstrated engagement of networks known to be important in depression. Current evidence supports a model whereby TMS normalizes network function gradually over the course of several treatments. This may, in turn, mediate its antidepressant effect. One strategy to optimize the antidepressant effect of TMS is to more precisely target networks relevant in depression. We propose methods to achieve this using functional and neurochemical imaging.


Identification of a soluble interleukin-8 inhibitor in the supernatant of polymorphonuclear leukocytes.
Interleukin-8 (IL-8) plays a crucial role in the pathogenesis of inflammatory and hyperproliferative diseases in various organs. The purpose of the present investigation was to establish whether there is any naturally occurring inhibitor of IL-8. Here we demonstrate that an IL-8 inhibitor (IL-8INH) is present in the supernatant of polymorphonuclear (PMN) leukocytes. The release of IL-8INH could be increased by stimulating the PMN leukocytes by concanavalin A. IL-81NH blocks the IL-8-induced chemotaxis and Candida albicans killing activity of PMN leukocytes and epidermal cells in vitro, and IL-8-induced neutrophil infiltration in the mouse ear in vivo. The mechanism of action of IL-8INH involves blocking of 125I-IL-8 binding to the IL-8 receptor. Binding of 125I-IL-8 to neutrophils could not be displaced by the IL-8INH, however, preincubation of 125I-IL-8 with IL-8INH increased binding inhibition, suggesting an interaction between IL-8 and the inhibitor. Crosslinking of 125I-IL-8 to IL-8INH shows that IL-8INH binds specifically to 125I-IL-8, and the IL-8INH protein has an apparent molecular weight of 52 kDa in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The partial purification of the IL-8INH on DEAE-Sephadex anion-exchange chromatography column also suggests a 50-60-kDa inhibitor protein which blocks IL-8-induced effects on neutrophils by binding to IL-8.


Circadian regulation of hemolymph and ovarian ecdysteroids during egg development in the insect Rhodnius prolixus (Hemiptera).
Ecdysteroids, classically studied as the molting hormones of insects, occur at lower levels in the adult stage, but their source and significance in adult physiology is debated. In Rhodnius prolixus, a blood meal initiates a cycle of egg development and ecdysteroids appeared in the hemolymph within 1-2h of feeding. Systematic changes in hemolymph ecdysteroid titer then occurred during egg development. There was a clear circadian rhythm in the hemolymph ecdysteroid titer throughout egg development. This is the first report of an ecdysteroid rhythm in any adult female insect. Of various tissues examined in vitro, only ovaries released ecdysteroids. The amounts released were adequate to account for observed hemolymph ecdysteroid titers. Therefore, ovaries are the primary, perhaps sole, source of hemolymph ecdysteroids. Ovaries in vitro showed a circadian rhythm of changes in ecdysteroid content and release that was in synchrony with the hemolymph ecdysteroid rhythm, indicating that ovarian ecdysteroid release drives the rhythm seen in the hemolymph. Potential regulation of ovarian ecdysteroids is discussed in relation to the known rhythms in prothoracicotropic hormone and insulin-like peptides that occur during egg development. The prospect of circadian regulation of egg development itself by hormones and/or an ovarian clock is also discussed.


[Intestinal schistosomiasis in the freshwater mangrove of Guadalupe (French Antilles). Ecology of the vector, Biomphalaria glabrata and its parasite Schistosoma mansoni (author's transl)].
In the freshwater mangrove of Dubelloy-Devarieux (Guadalupe), the dynamics of populations of B. glabrata and the transmission of S. mansoni, mostly depends on the alternation of dry and rainy season. The flooding of the mangrove (in september), permits a yearly renewal of the malacological populations. The sizes analysis of the snails shows that the life cycle of B. glabrata include two rainy seasons separated by one dry season. The prevalence of B. glabrata (0,25%) and cercariae densities (0,8 c/l) are very slow. The acrophase of the rhythm of presence in standing waters is reached at 2 pm. Men and rats are infected. The infections of rats is of 20% at the beginning of the rainy season and of 100% at the end of the rainy season. Principal factors involved in the infection of rats are discussed.


Procalcitonin for differential diagnosis of graft rejection and infection in patients with heart and/or lung grafts.
Investigation of the reliability of Procalcitonin (PCT) for differential diagnosis of acute rejections and non-viral infections in heart and lung transplanted patients. Retrospective study. Transplant intensive care unit (ICU) at a university hospital. 57 heart, 18 lung and 3 heart-lung transplant patients. PCT was measured in plasma samples of heart and lung transplanted patients using a commercial immuno-luminescence assay and was compared with values of C-reactive protein (CRP) and leukocytes (WBC). PCT was elevated in patients suffering from bacterial and fungal infections. The magnitude of values was clearly associated with the severity of the infection. Rejections and viral infections did not interfere with the PCT release. PCT is a reliable predictor with discriminating power for non-viral systemic infections in patients after heart and/or lung transplantation. PCT allows an early differential diagnosis between rejection (AR) and bacterial/fungal infection (IF) and thus a rapid and focused therapeutic intervention. It avoids unnecessary antibiotic treatment which could be toxic for the graft itself in patients with rejection only. PCT provides vital information early to clinicians and allows them to improve the management of bacterial/fungal infections in immunocompromized transplant patients. PCT thus facilitates and improves the outcome of survival rate and the quality of life in the postoperative period of patients with heart and/or lung grafts.


Cerebral ganglioglioma. A Golgi study.
The morphological characteristics of neurons revealed by Golgi's method are reported in a case of cerebral ganglioglioma. Spindle-shaped (leptodendritic) neurons and radiated type I neurons form the bulk of this tumour. According to Ramon-Moliner (1968) isodendritic neurons (both leptodendritic and radiate type I) are philogenetically primitive cells and differ greatly from those observed in most of the deep cerebral nuclei of the mammalian's brain.


Man vs. machine: comparison of pharmacogenetic expert counselling with a clinical medication support system in a study with 200 genotyped patients.
Medication problems such as strong side effects or inefficacy occur frequently. At our university hospital, a consultation group of specialists takes care of patients suffering from medication problems. Nevertheless, the counselling of poly-treated patients is complex, as it requires the consideration of a large network of interactions between drugs and their targets, their metabolizing enzymes, and their transporters, etc. PURPOSE: This study aims to check whether a score-based decision-support system (1) reduces the time and effort and (2) suggests solutions at the same quality level. A total of 200 multimorbid, poly-treated patients with medication problems were included. All patients were considered twice: manually, as clinically established, and using the Drug-PIN decision-support system. Besides diagnoses, lab data (kidney, liver), phenotype (age, gender, BMI, habits), and genotype (genetic variants with actionable clinical evidence I or IIa) were considered, to eliminate potentially inappropriate medications and to select individually favourable drugs from existing medication classes. The algorithm is connected to automatically updated knowledge resources to provide reproducible up-to-date decision support. The average turnaround time for manual poly-therapy counselling per patient ranges from 3 to 6 working hours, while it can be reduced to ten minutes using Drug-PIN. At the same time, the results of the novel computerized approach coincide with the manual approach at a level of > 90%. The holistic medication score can be used to find favourable drugs within a class of drugs and also to judge the severity of medication problems, to identify critical cases early and automatically. With the computerized version of this approach, it became possible to score all combinations of all alternative drugs from each class of drugs administered ("personalized medication landscape ") and to identify critical patients even before problems are reported ("medication alert"). Careful comparison of manual and score-based results shows that the incomplete manual consideration of genetic specialties and pharmacokinetic conflicts is responsible for most of the (minor) deviations between the two approaches. The meaning of the reduction of working time for experts by about 2 orders of magnitude should not be underestimated, as it enables practical application of personalized medicine in clinical routine.


Molecular cloning of human GABABR1 and its tissue distribution.
GABABR1 clones were isolated from a human cerebellum library. The human sequence is very similar to rat GABABR1 with the cDNAs sharing 91.3% sequence identity and the receptors sharing 98.6% amino acid sequence identity. Northern blotting has shown that the receptor is brain-specific with a widespread distribution throughout the brain but none detected in the spinal cord.


Influence of digoxin on sinus node function after pharmacologic autonomic blockade.
The effect of iv digoxin on normal sinus node function was studied after pharmacologic autonomic blockade (AB) in ten patients. Sinus cycle length (SCL), sinus node recovery time (SNRT) and sinoatrial conduction time (SACT) were determined before and after AB with propranolol (0.2 mg/kg body weight) and atropine sulfate (0.04 mg/kg body weight) iv, and 15 min, 30 min, and 45 min after 1 mg iv digoxin. AB resulted in a significant decrease (P less than 0.01) in SCL (916 +/- 158 to 716 +/- 120 ms), in SNRT (1,229 +/- 221 to 871 +/- 190 ms), and in SACT (79 +/- 34 to 44 +/- 10 ms). Fifteen minutes after iv digoxin there was no significant change observed in SCL (716 +/- 120 to 708 +/- 92 ms), in SNRT (871 +/- 190 to 864 +/- 148 ms), or in SACT (44 +/- 10 to 46 +/- 15 ms). Similar results were obtained 30 min after digoxin administration. It is concluded that a single therapeutic dose of digoxin has no direct effect on electrophysiologic parameters of normal intrinsic sinus node function.


Structural and functional studies of a large winged Z-DNA-binding domain of Danio rerio protein kinase PKZ.
The Z-DNA-binding domain of PKZ from zebrafish (Danio rerio; drZαPKZ ) contains the largest β-wing among known Z-DNA-binding domains. To elucidate the functional implication of the β-wing, we solved the crystal structure of apo-drZαPKZ . Structural comparison with its Z-DNA-bound form revealed a large conformational change within the β-wing during Z-DNA binding. Biochemical studies of protein mutants revealed that two basic residues in the β-wing are responsible for Z-DNA recognition as well as fast B-Z transition. Therefore, the extra basic residues in the β-wing of drZαPKZ are necessary for the fast B-Z transition activity.


A global bibliometric and visualized analysis of bacteria-mediated cancer therapy.
Bacteriotherapy has proved to be a powerful tool to fight against cancer. Herein, we used VOSviewer, CiteSpace, and Python to perform the first global bibliometric analysis of the literature from 2012 to 2021 on bacteria-mediated cancer therapy. Based on the results, East Asia and North America contributed the most publications to this research area. Additionally, the keyword analysis indicated that immunotherapy and nanoparticle (NP)-based drug delivery systems have long been popular topics in cancer bacteriotherapy, whereas the gut microbiota and probiotics are emerging research hotspots. This study provides crucial insights into the historical development of bacteria-mediated cancer therapy from 2012 to 2021, which will be helpful for scientists to conduct further investigation into this promising field.


Bone mineral density and intervertebral disc height in type 2 diabetes.
Studies of the effect of type 2 diabetes (T2D) on bone mineral density (BMD have produced conflicting results, possibly due to failure to adjust for potential confounding factors. Nonetheless, T2D has consistently been associated with increased fracture risk, suggesting that other factors might play a role. This study assesses the relationship between T2D and BMD at the femoral neck and spine in diabetic and non-diabetic subjects, after adjusting for multiple covariates which may affect BMD. Intervertebral disc height was also investigated in view of its possible relation to fracture risk. A cross-sectional study of 100 patients with T2DM of at least 5 years duration and 86 non-diabetic subjects was carried out. There were no significant differences in T scores in either the spine or femoral neck after adjustment for potential confounding variables between T2D subjects and controls. Diabetic patients had a statistically lower intervertebral disc height between the 2nd and 3rd lumbar vertebrae (D3) after adjustment for potential confounders (p=0.004). Urinary albumin:creatinine ratio, total cholesterol, LDL-cholesterol and cigarette smoking were independently associated with lower height of D3 in diabetic subjects. There is no significant independent association between T2D and BMD. However we found a novel association of significantly lower disc height in patients with T2D. This may contribute to the increased vertebral fracture risk in subjects with T2D. Further studies are needed to investigate the relationship of disc height, T2D and fracture risk.


Chemosensitive serotonergic neurons are closely associated with large medullary arteries.
We have previously shown that serotonergic neurons of the medulla are strongly stimulated by an increase in CO(2), suggesting that they are central respiratory chemoreceptors. Here we used confocal imaging and electron microscopy to show that neurons immunoreactive for tryptophan hydroxylase (TpOH) are tightly apposed to large arteries in the rat medulla. We used patch-clamp recordings from brain slices to confirm that neurons with this anatomical specialization are chemosensitive. Serotonergic neurons are ideally situated for sensing arterial blood CO(2), and may help maintain pH homeostasis via wide-ranging effects on brain function. The results reported here support a recent proposal that sudden infant death syndrome (SIDS) results from a developmental abnormality of medullary serotonergic neurons.


Targeting p53, hdm2, and CD19: vaccination and immunologic strategies.
Peptides presented by class I major histocompatibility complex (MHC) molecules and derived from normal self-proteins that are expressed at elevated levels by cells from a variety of human (Hu) malignancies provide, in theory, potential target antigens for a broad-spectrum, cytotoxic T lymphocyte (CTL)-based immunotherapy of cancer and hematologic malignancies. However, as such tumor- and leukemia-associated self-proteins are also expressed at low levels in some types of normal tissues, such as thymus, spleen and lymphohemopoietic cells, these self-MHC-self-peptide complexes may also represent thymic and/or peripheral tolerogens, thereby preventing immune responses. This is particularly true for class I MHC-peptide complexes expressed by bone marrow-derived cells in the thymus, as such expression would cause negative selection of immature thymic T cells with high avidity for self-MHC-self-peptide complexes. This intrathymic deletion of potentially self-reactive T cells could result in a peripheral T cell repertoire purged of CTL precursors with sufficient avidity to recognize natural tumor associated self-epitopes presented by class I MHC molecules on tumor cells. HLA-transgenic (Tg) mice provide the basis of an experimental strategy that exploits species differences between Hu and murine (Mu) protein sequences in order to circumvent self-tolerance and obtain HLA-restricted CTL specific for epitopes derived from tumor- and leukemia-associated Hu self proteins, such as p53, Her-2/neu, hdm2 and CD19.


Determination of androstenone in pig fat using packed column supercritical fluid chromatography-mass spectrometry.
Packed column supercritical fluid chromatography (SFC) in combination with atmospheric pressure chemical ionisation mass spectrometry was applied to the analysis of androstenone in pig fat samples. Liquefied fat samples were dissolved in dichloromethane and analysed directly by SFC without any sample purification. Chromatographic separation was achieved with a density/pressure gradient using pure carbon dioxide as the mobile phase and the analysis resulted in a quantitation limit of 0.25 microg/g with 1 microl injection volume. Good agreement was found between the SFC method and time-resolved fluoroimmunoassay by the analysis of 15 boar back fat samples.


The influence of gender on survival after heart transplantation.
Because of a shortage of deceased donors, more than one-third of patients die during the waiting period for transplantation. This study was conducted to analyze the influence of gender on survival after heart transplantation. We retrospectively reviewed the recipients after primary orthotopic heart transplantation. According to gender, patients were divided into four groups: male donor to male recipient, male donor to female recipient, female donor to male recipient, and female donor to female recipient. Kaplan-Meier survival curves were plotted with log-rank tests. Cox regression analysis with dummy variables were used to examine the effects of donor gender, recipient gender, and donor-recipient gender combinations on survival after heart transplantation. The data did not show any significant effect of donor gender, recipient gender, or donor-recipient gender combinations on patient survival, using the methods of log-rank test and Cox regression with dummy variables. Based on our results, we concluded that gender was not an important factor in organ allocation.


Prevalence and risk factors of gammaherpesvirus infection in domestic cats in Central Europe.
Gammaherpesviruses (GHVs) are a large group of dsDNA viruses that can infect humans and several animal species. The two human GHVs, Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus are known for their oncogenic properties in individuals with immunodeficiency. Recently, the first feline GHV, Felis catus gammaherpesvirus 1 (FcaGHV1) was discovered and frequently found in domestic cats in Australia, Singapore and the USA. FcaGHV1 is more likely to be detected in cats co-infected with the feline immunodeficiency virus (FIV). The prevalence of FcaGHV1 in pet cats from Germany and Austria was 16.2 % (95 % CI = 12.38-20.02). The odds for GHV infection were greater for FIV positive (OR = 4.5), male (OR = 13.32) and older (OR = 2.36) cats. Furthermore, FcaGHV1 viral loads were significantly higher in FIV-infected cats compared to matched controls. GHV infections are common in domestic cats in Central Europe. The worldwide distribution of FcaGHV1 can be assumed. A potential role as a co-factor in FIV-induced pathogeneses is supported.


Exploration and comparison of methods for combining population- and family-based genetic association using the Genetic Analysis Workshop 17 mini-exome.
We examine the performance of various methods for combining family- and population-based genetic association data. Several approaches have been proposed for situations in which information is collected from both a subset of unrelated subjects and a subset of family members. Analyzing these samples separately is known to be inefficient, and it is important to determine the scenarios for which differing methods perform well. Others have investigated this question; however, no extensive simulations have been conducted, nor have these methods been applied to mini-exome-style data such as that provided by Genetic Analysis Workshop 17. We quantify the empirical power and false-positive rates for three existing methods applied to the Genetic Analysis Workshop 17 mini-exome data and compare relative performance. We use knowledge of the underlying data simulation model to make these assessments.


Structural comparison of the active site channels in rodent and primate vascular adhesion protein-1.
In this study, we have made homology models of mouse, rat, and monkey vascular adhesion protein-1 (VAP-1) to reveal basis for the species-specific ligand recognition of VAP-1. Based on the structural comparisons, rodent VAP-1s have a narrower active site channel than primate VAP-1s. The variable residues in mouse and rat VAP-1, Phe447 from arm I and the polar residues from the first α-helix of the D3 domain together with C-terminal residues are likely to affect ligand recognition and binding.


An integrative transcriptomic analysis reveals p53 regulated miRNA, mRNA, and lncRNA networks in nasopharyngeal carcinoma.
It has been reported that p53 dysfunction is closely related to the carcinogenesis of nasopharyngeal carcinoma (NPC). Recently, an increasing body of evidence has indicated that microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) participate in p53-associated signaling pathways and, in addition to mRNAs, form a complex regulation network to promote tumor occurrence and progression. The aim of this study was to elucidate the p53-regulated miRNAs, mRNAs, and lncRNAs and their regulating networks in NPC. Firstly, we overexpressed p53 in the NPC cell line HNE2 and performed transcriptomic gene expression profiling (GEP) analysis, which included miRNAs, mRNAs, and lncRNAs, using microarray technology at 0, 12, 24, and 48 h after transfection. There were 38 miRNAs (33 upregulated and 5 downregulated), 2107 mRNAs (296 upregulated and 1811 downregulated), and 1190 lncRNAs (133 upregulated and 1057 downregulated) that were significantly dysregulated by p53. Some of the dysregulated molecules were confirmed by quantitative real-time polymerase chain reaction (qRT-PCR). Then, we integrated previously published miRNAs, mRNAs, and lncRNAs GEP datasets from NPC biopsies to investigate the expression of these p53 regulated molecules and found that 7 miRNAs, 218 mRNAs, and 101 lncRNAs regulated by p53 were also differentially expressed in NPC tissues. Finally, p53-regulated miRNA, mRNA, and lncRNA networks were constructed using bioinformatics methods. These miRNAs, mRNAs, and lncRNAs may participate in p53 downstream signaling pathways and play important roles in the carcinogenesis of NPC. Thorough investigations of their biological functions and regulating relationships will provide a novel view of the p53 signaling pathway, and the restoration of p53 functioning or its downstream gene regulating network is potentially of great value in treating NPC patients.


Investigation of resistance mechanisms to fomesafen in Ipomoea nil from China.
Recently, the herbicide fomesafen has frequently failed to control the troublesome weed Ipomoea nil in soybean fields in Liaoning Province, China. Hence, we collected 10 suspected resistant populations and evaluated their sensitivity to fomesafen. The results revealed various degrees of Ipomoea nil resistance to fomesafen, with a resistance index of 2.88 to 22.43; the highest value occurred in the LN3 population. Therefore, the mechanisms of the resistance in LN3 to fomesafen were explored. After fomesafen treatment, the expression levels of InPPX1 and InPPX2 genes were 4.19- and 9.29-fold higher, respectively, in LN3 than those in the susceptible (LN1) population. However, mutations and copy number variations were not detected between the two populations. Additionally, malathion pretreatment reduced the dose necessary to halve the growth rate of LN3 by 58%. Liquid chromatography with tandem mass spectrometry demonstrated that metabolism of fomesafen was significantly suppressed by malathion. Moreover, LN3 displayed increased reactive oxygen species scavenging capacity, which was represented by higher superoxide dismutase and peroxidase activities after fomesafen application than those in LN1. An orthogonal partial least squares-discriminant analysis revealed that the high resistance in LN3 could be attributed mainly to enhanced metabolism. Fortunately, the fomesafen-resistant I. nil remained sensitive to 2,4-D-ethylhexylester and bentazon, providing methods for its control.


Correction to: The Expression of Immunomodulation-Related Cytokines and Genes of Adipose- and Bone Marrow-Derived Human Mesenchymal Stromal Cells from Early to Late Passages.
[This corrects the article DOI: 10.1007/s13770-018-0147-5.].


Possible role of an iron-oxygen complex in 4(S)-4-hydroxyochratoxin a formation by rat liver microsomes.
Rat liver microsomes were examined for their ability to oxidize the mycotoxin ochratoxin A (OTA) to 4(R)-4-hydroxyochratoxin A [(R)-4-OH-OTA] and 4(S)-4-hydroxyochratoxin A [(S)-4-OH-OTA] and to induce OTA-dependent lipid peroxidation. Microsomes isolated from rats pretreated with pregnenolone-16 alpha-carbonitrile greatly induced both (R)-4-OH-OTA and (S)-4-OH-OTA formation whereas isoniazid pretreatment primarily induced (S)-4-OH-OTA. (R)-4-OH-OTA and (S)-4-OH-OTA formation showed significant differences with respect to pH optima, effect of antioxidants, and iron chelators. (R)-4-OH-OTA showed a pH optimum of 6.5 and was not inhibited by the antioxidants butylated hydroxyanisole or N,N-diphenyl-1,4-phenylenediamine or the iron chelators. Desferal or bathophenanthrolinedisulfonic acid. In contrast, both (S)-4-OH-OTA and lipid peroxidation showed a pH optimum of 7.0 and both activities were sensitive to inhibition by the above antioxidants and iron chelators. Lipid peroxidation was not involved in (S)-4-OH-OTA formation since addition of linoleic acid hydroperoxide to microsomes did not give rise to (S)-4-OH-OTA. Cytochrome P450 appeared to be essential since other hemoproteins like horseradish peroxidase and hemoglobin were ineffective in metabolizing OTA in the presence of hydroperoxides. The results suggest that (R)-4-OH-OTA is formed by normal mixed-function oxidation but that (S)-4-OH-OTA formation may involve free iron. It is likely that an active Fe2(+)-oxygen complex, formed via NADPH-cytochrome P450 reductase and cytochrome P450-dependent reduction of free Fe3+ followed by oxygen binding, serves as the species inducing lipid peroxidation and at least part of (S)-4-OH-OTA formation.


Anthropogenic rare earth elements in urban lakes: Their spatial distributions and tracing application.
Anthropogenic activities associated with various new technologies are increasingly disrupting the geochemical cycles of rare earth elements (REEs). For example, samarium (Sm) and gadolinium (Gd) have emerged as microcontaminants in the natural waters of developed areas. Surface water samples of 13 urban lakes were collected in Wuhan, the largest city in central China, with a population of over 11 million. The aim of this study was to examine to what extent REE anomalies occur and the relationship between the concentration of anthropogenic REEs in lakes and the surrounding environment. In this study, based on land-use type and point of interest (POIs) data, buffer extraction, density estimation and Spearman correlation analysis were first proposed to identify different sources of anthropogenic REEs, which mainly included hospitals, factories, population, urban land and cropland. The PAAS-normalized REE patterns indicate that all lake samples display pronounced positive Sm and Gd anomalies, ranging from 5.92 to 19.88 and 1.73 to 14.97, respectively. Spearman correlation analysis showed that hospital density was positively correlated with anthropogenic Gd concentration, and a positive relationship between proportion of cropland and the concentration of anthropogenic Sm. By utilizing Gdanth, Smanth, and the conventional ion ratio (NO3-/Cl-), a three-dimensional tracer system was established, and the system accurately obtained a characterization of the impact of WWTPs, hospitals, factories and agriculture on the lakes. Moreover, the results from this hydrochemical method were consistent with the analysis of geographic information systems, which indicated that this anthropogenic contaminant as a tracer was reliable for analysing the source of urban water pollution.


Fractionated anthracycline therapy in acute myeloblastic leukaemia in adults.
A total of nine adults with newly diagnosed acute myeloblastic leukaemia (AML) and seven with relapsed disease were treated with fractionated daunorubicin in combination with cytosine arabinoside and 6-thioguanine. Remissions were seen in 89% and 57%, respectively. The side effects associated with bolus injections of daunorubicin were much less severe with fractionated treatment, and there was no significant cardiotoxicity despite total doses of up to 1363 mg/m2 daunorubicin. These results show that fractionated anthracyclines are effective in the treatment of AML and that this mode of administration may permit an upward revision of the accepted dose limits for anthracyclines.


Human CYP1A1 variants lead to differential eicosapentaenoic acid metabolite patterns.
To answer the question whether the most common allelic variants of human CYP1A1, namely CYP1A1.1 (wild type), CYP1A1.2 (Ile462Val), and CYP1A1.4 (Thr461Asn), differ in their catalytic activity towards eicosapentaenoic acid (EPA), in vitro enzymatic assays were performed in reconstituted CYP1A1 systems. All CYP1A1 variants catalyzed EPA epoxygenation and hydroxylation to 17(R),18(S)-epoxyeicosatetraenoic acid (17(R),18(S)-EETeTr) and 19-OH-EPA, yet with varying catalytic efficiency and distinct regiospecificity. CYP1A1.1 and CYP1A1.4 formed 17(R),18(S)-EETeTr as main product (K(m)=53 and 50 microM; V(max)=0.60 and 0.50 pmol/min/pmol; V(max)/K(m)=0.11 and 0.10 microM(-1)min(-1), respectively), followed by 19-OH-EPA (K(m)=76 and 93 microM; V(max)=0.37 and 0.37 pmol/min/pmol; V(max)/K(m)=0.005 and 0.004 microM(-1)min(-1), respectively). The variant CYP1A1.2 produced almost equal amounts of both metabolites, but its catalytic efficiency for hydroxylation was five times higher (K(m)=66 microM; V(max)=1.7 pmol/min/pmol; V(max)/K(m)=0.026 microM(-1)min(-1)) and that for epoxygenation was twice higher (K(m)=66 microM; V(max)=1.5 pmol/min/pmol; V(max)/K(m)=0.023 microM(-1)min(-1)) than those of the wild-type enzyme. Thus, the Ile462Val polymorphism in human CYP1A1 affects EPA metabolism and may contribute to interindividual variance in the local production of physiologically active fatty acid metabolites in the cardiovascular system and other extrahepatic tissues, where CYP1A1 is expressed or induced by polycyclic aromatic hydrocarbons and other xenobiotics.


Isoledene from Mesua ferrea oleo-gum resin induces apoptosis in HCT 116 cells through ROS-mediated modulation of multiple proteins in the apoptotic pathways: A mechanistic study.
Colorectal cancer (CRC) is one of the most common human malignant tumors worldwide. Arising from the transformation of epithelial cells in the colon and/or rectum into malignant cells, the foundation of CRC pathogenesis lies in the progressive accumulation of mutations in oncogenes and tumor-suppressor genes, such as KRAS and APC. Resistance to apoptosis is one of the key mechanisms in the development of CRC as it is for any other kind of cancer. Natural products have been shown to induce the expression of apoptosis regulators that are blocked in cancer cells. In the present study, a series of in vitro assays were employed to study the apoptosis-inducing attributes of Isoledene rich sub-fraction (IR-SF) collected from the oleo-gum resin of M. ferrea. Data obtained, showed that IR-SF inhibited cell proliferation and induced typical apoptotic changes in the overall morphology of all the CRC cell lines tested. Fluorescent staining assays revealed characteristic nuclear condensation, and marked decrease in mitochondrial outer membrane potential in the treated cells. In addition, an increment in the levels of ROS, caspase-8, -9 and -3 was observed. Proteomic analysis revealed that IR-SF up-regulated the expression of pro-apoptotic proteins, i.e., Bid, Bim and cytochrome c. Cytochrome c in turn activated caspases cascade resulting in the induction of apoptosis. Moreover, IR-SF significantly down-regulated Bcl-2, Bcl-w, survivin, xIAP and HSPs pro-survival proteins and induced DNA fragmentation and G0/G1-phase arrest in HCT 116 cells. Chemical characterization of IR-SF by GC-MS and HPLC methods identified Isoledene as one of the major compounds. Altogether, results of the present study demonstrate that IR-SF may induce apoptosis in human colorectal carcinoma cells through activation of ROS-mediated apoptotic pathways.


[Clinical characteristics and genetic analysis of two children with neonatal severe hyperparathyroidism].
To explore the clinical features and genetic variants in two children with neonatal severe hyperparathyroidism (NSHPT). Two children who were diagnosed with NSHPT at the Children's Hospital Affiliated to Xi'an Jiaotong University respectively in August 2019 and April 2022 were selected as the study subjects. Clinical data were collected, and both children were subjected to whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing. The main clinical features of the two children have included growth delay, hypotonia, hypercalcemia, hypophosphatemia, hyperparathyroid hormonemia, and renal calcium deposition. WES results showed that child 1 has harbored a homozygous c.1378_1G>A splicing variant of the CASR gene, which was unreported previously, whilst child 2 has harbored a homozygous c.2038C>T missense variant of the CASR gene, which was known to be likely pathogenic. Sanger sequencing confirmed that the parents of both children were heterozygous carriers. The homozygous c.1378_1G>A and c.2038C>T variants of the CASR gene probably underlay the NSHPT in the two children. Discovery of the c.1378_1G>A variant has enriched the mutational spectrum of the CASR gene.


Mechanisms for motor timing in the cerebellar cortex.
In classical eyeblink conditioning a subject learns to blink to a previously neutral stimulus. This conditional response is timed to occur just before an air puff to the eye. The learning is known to depend on the cerebellar cortex where Purkinje cells respond with adaptively timed pauses in their spontaneous firing. The pauses in the inhibitory Purkinje cells cause disinhibition of the cerebellar nuclei, which elicit the overt blinks. The timing of a Purkinje cell response was previously thought to require a temporal code in the input signal but recent work suggests that the Purkinje cells can learn to time their responses through an intrinsic mechanism that is activated by metabotropic glutamate receptors (mGluR7).


Differences in the self-depictions of female alcoholics and psychiatric outpatients: towards a depiction of the modal female alcoholic.
Forty-one Minnesota Multiphasic Personality Inventory (MMPI) items that differentiated modal female alcoholics from modal nonsubstance-abusing psychiatric outpatients at the p less than .0001 level of significance were located. A principal factor analysis of the 41 X 41 item-intercorrelation matrix yielded three factors which were labeled (1) Deviant Thrill-Seeking, (2) Remorseful Intrapunitiveness and (3) Blackouts. Nonmodal alcoholics, who comprised approximately 20% of the present sample, were found to be indistinguishable from modal psychiatric outpatients except for their excessive consumption of alcohol.


Deep learning-based detection system for multiclass lesions on chest radiographs: comparison with observer readings.
To investigate the feasibility of a deep learning-based detection (DLD) system for multiclass lesions on chest radiograph, in comparison with observers. A total of 15,809 chest radiographs were collected from two tertiary hospitals (7204 normal and 8605 abnormal with nodule/mass, interstitial opacity, pleural effusion, or pneumothorax). Except for the test set (100 normal and 100 abnormal (nodule/mass, 70; interstitial opacity, 10; pleural effusion, 10; pneumothorax, 10)), radiographs were used to develop a DLD system for detecting multiclass lesions. The diagnostic performance of the developed model and that of nine observers with varying experiences were evaluated and compared using area under the receiver operating characteristic curve (AUROC), on a per-image basis, and jackknife alternative free-response receiver operating characteristic figure of merit (FOM) on a per-lesion basis. The false-positive fraction was also calculated. Compared with the group-averaged observations, the DLD system demonstrated significantly higher performances on image-wise normal/abnormal classification and lesion-wise detection with pattern classification (AUROC, 0.985 vs. 0.958; p = 0.001; FOM, 0.962 vs. 0.886; p < 0.001). In lesion-wise detection, the DLD system outperformed all nine observers. In the subgroup analysis, the DLD system exhibited consistently better performance for both nodule/mass (FOM, 0.913 vs. 0.847; p < 0.001) and the other three abnormal classes (FOM, 0.995 vs. 0.843; p < 0.001). The false-positive fraction of all abnormalities was 0.11 for the DLD system and 0.19 for the observers. The DLD system showed the potential for detection of lesions and pattern classification on chest radiographs, performing normal/abnormal classifications and achieving high diagnostic performance. • The DLD system was feasible for detection with pattern classification of multiclass lesions on chest radiograph. • The DLD system had high performance of image-wise classification as normal or abnormal chest radiographs (AUROC, 0.985) and showed especially high specificity (99.0%). • In lesion-wise detection of multiclass lesions, the DLD system outperformed all 9 observers (FOM, 0.962 vs. 0.886; p < 0.001).


W-band PELDOR with 1 kW microwave power: molecular geometry, flexibility and exchange coupling.
A technique that is increasingly being used to determine the structure and conformational flexibility of biomacromolecules is Pulsed Electron-Electron Double Resonance (PELDOR or DEER), an Electron Paramagnetic Resonance (EPR) based technique. At X-band frequencies (9.5 GHz), PELDOR is capable of precisely measuring distances in the range of 1.5-8 nm between paramagnetic centres but the orientation selectivity is weak. In contrast, working at higher frequencies increases the orientation selection but usually at the expense of decreased microwave power and PELDOR modulation depth. Here it is shown that a home-built high-power pulsed W-band EPR spectrometer (HiPER) with a large instantaneous bandwidth enables one to achieve PELDOR data with a high degree of orientation selectivity and large modulation depths. We demonstrate a measurement methodology that gives a set of PELDOR time traces that yield highly constrained data sets. Simulating the resulting time traces provides a deeper insight into the conformational flexibility and exchange coupling of three bisnitroxide model systems. These measurements provide strong evidence that W-band PELDOR may prove to be an accurate and quantitative tool in assessing the relative orientations of nitroxide spin labels and to correlate those orientations to the underlying biological structure and dynamics.


Follow-up study of 232 patients with occupational asthma caused by western red cedar (Thuja plicata).
A total of 232 patients with red cedar asthma diagnosed by inhalation provocation tests were observed an average of 4 years after the initial diagnosis. The status during the follow-up examination was as follows: 96 patients continued to work with red cedar, and 136 left the industry and had no further exposure to red cedar in their jobs or hobbies. Of the 136 patients who left the industry, only 55 (40.4%) recovered completely, whereas the remaining 81 (59.6%) continued to experience attacks of asthma of varying severity. The initial pulmonary function tests were significantly higher among the asymptomatic group compared to the symptomatic group (FEV1 99.3 +/- 2.7% versus 90.5 +/- 2.2% predicted, respectively). Methacholine PC20 during the initial examination was higher among the asymptomatic group than in the symptomatic group (1.46 +/- 3.96 mg/ml versus 0.77 +/- 4.52 mg/ml, respectively). These findings indicate that the patients in the asymptomatic group were diagnosed at an earlier stage of the disease. This observation was confirmed by the significantly shorter duration of symptoms before diagnosis among the asymptomatic patients compared to the symptomatic patients (1.6 +/- 1.9 versus 2.6 +/- 4.3 years). Race, smoking status, immediate skin reactivity, and presence of plicatic acid-specific IgE antibodies did not influence the outcome of these patients. Of the 96 patients who continued to work with red cedar, 47 were exposed daily, whereas 41 were exposed intermittently.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of high pressure gaseous carbon dioxide on the germination of bacterial spores.
Effect of high pressure gaseous carbon dioxide treatment (HGCT) at 6.5 MPa, 35 degrees C on the germination of bacterial spores was investigated. Germination of bacterial spores was estimated by the decrease of heat tolerance. Approximately, 40% of Bacillus coagulans and 70% of Bacillus licheniformis were germinated by HGCT for 120 min at 35 degrees C, respectively. Germination was confirmed by phase contrast microscopy. The effect of hydrostatic pressure treatment (HPT) at 6.5 MPa, 35 degrees C on the germination of B. coagulans and B. licheniformis spores were also investigated. Spores did not germinate by HPT alone at 6.5 MPa for 120 min.


[Reopening of completely closed aortocoronary venous bypasses using angioplasty and 24-hour local fibrinolysis].
Recent occlusion of aortocoronary venous bypass grafts had occurred in three patients, aged between 64 and 67 years. In all three recanalization was achieved after 8 hours, two and five days, respectively, of coronary angioplasty combined with local urokinase infusion for 24 hours. The procedure consisted of passing a guide-wire through the occluded bypass graft, the tip of the wire then being advanced to the periphery of the native coronary artery. The balloon was then repeatedly dilated along the length of the graft. Primary opening was not achieved in one of the grafts, and the other two closed again, despite repeated and prolonged balloon dilatation. In all three patients a coronary infusion catheter was then placed into the graft lumen and urokinase (3 mill. units) infused over 24 hours. An angiogram 24 hours later demonstrated an open bypass graft (residual stenosis < 50%). Angiography 9 to 14 weeks later revealed restenosis in one case, but it was reopened by balloon dilatation and stent insertion, while the other two had remained open without significant stenosis.


Plasma concentrations of voriconazole in falcons.
Doses of 12.5 mg voriconazole/kg bodyweight administered every 12 hours by crop gavage to six falcons for 14 days provided peak plasma concentrations of more than 1 microg/ml, but the trough concentrations were lower and sometimes undetectable. Administering the same doses incorporated into meat that was fed to one falcon for seven days and to three falcons for up to 91 days provided similar plasma concentrations.


Reliability and Reproducibility of Subject Positioning with EOS Low-Dose Biplanar X-ray.
EOS low-dose biplanar X-ray used with tantalum bead implantation is an appealing imaging modality to evaluate limb length and physeal growth due its relatively low radiation exposure, excellent inter- and intra-observer reliability, and minimal magnification/shrinkage error. The purpose of this study was to establish the error in total length and inter-bead distances using EOS and tantalum beads due to variable positioning in the EOS gantry, by assessing variation in measurements made on the same subject repeatedly positioning by one positioner (intra-positioner measurement error) and variation in measurements made on the same subject with positioning by multiple positioners (inter-positioner measurement error). Tantalum bead markers were placed about the distal femoral physis of a cadaveric lamb femur. Three investigators positioned the femur in the EOS gantry 10 times, totaling 30 EOS scans. Total limb length and inter-bead distances were measured on AP and lateral views; mean and standard error were calculated. A random effects analysis of variance for nested data was used to determine the proportion of variation due to differences between positioners and differences between positioning by the same positioner. Intra-positioner measurement error ranged from 0.01 to 0.06 mm. Inter-positioner measurement error ranged from 0.00 to 0.09 mm. EOS has relatively low radiation and allows standing assessment of limb length and alignment. In this study, length measurements and inter-bead distances demonstrated minimal error due to positioning in the EOS gantry, documenting that there is minimal error from positioning, minimal magnification/shrinkage error, and exceptional inter and intra-rater reliability. EOS is the preferred method for length and angular measurements, and with tantalum beads, is ideal for measuring growth about the physis.


Effect of surfactant assisted ultrasonic pretreatment on production of volatile fatty acids from mixed food waste.
In this study, the potential effect of surfactant assisted ultrasonic pretreatment on mixed food waste was investigated. Surfactants, such as Rhamnolipid, Sodium dodecyl sulfate; Glucopon and Triton X 100 were evaluated in this work. Among them, the maximum solubilization of chemical oxygen demand of 45.5 % and the highest release of soluble COD of 31 g/L were observed for ultrasonication assisted by Triton X 100 at a dose of 0.01 g/g TS in 30 min. The presence of a surfactant also reduced 27.5 % of energy demand when compared to ultrasonic pretreatment alone. Compared to the non-pretreated samples after anaerobic digestion, ultrasonication assisted by Triton X 100 led to 95 % increase of volatile fatty acid titers and 83 % increase of carbon conversion efficiency. Thus, sonication with the addition of Triton X 100 was proven to be highly effective toward increasing digestibility of and yield of volatile fatty acid from mixed food waste.


Meta-analysis demonstrates Gly482Ser variant of PPARGC1A is associated with components of metabolic syndrome within Asian populations.
To determine the association of peroxisome proliferator activated receptor gamma coactivator 1 Gly482Ser variant with components of metabolic syndrome. A systematic search was carried out using Web of Science, PubMed, EMBASE and the Cochrane library using the key words: Peroxisome proliferator activator receptor gamma coactivator 1, PPARGC1A, PGC-1, PGC-1alpha, and PGC1alpha alone or with polymorphism, Gly482Ser and rs8192678. Data from 19 articles generated 28 separate data sets. Under the recessive model fasting plasma glucose was significantly lower in AA genotypes when compared to GG + GA in the total sample group and in non-Asian group (p < .001). The AA genotype showed significantly lower levels of total cholesterol compared to GG + GA genotype using the recessive model with the non-Asian group (p < .05). Under the dominant model, body mass index of the GG genotype was significantly higher in Asian subgroups (p < .05). PPARGC1A Gly482Ser variant impacts differently in Asian population groups.


PCSK9 Inhibition in Patients After Heart Transplantation: a Retrospective Review and Literature Analysis.
Following cardiac transplantation, patients have an increased risk of developing cardiac allograft vasculopathy and atherosclerotic cardiovascular disease. Therefore, aggressive lipid management is indicated. Some patients do not achieve optimal lipid profiles with statin monotherapy, however, or discontinue statins due to intolerance. In this review, we investigated the use of PCSK9 inhibitors as an alternative treatment for hyperlipidemia following cardiac transplantation. Nine published articles were identified that included 110 patients treated with alirocumab or evolocumab after cardiac transplantation. PCSK9 inhibitors were tolerated by all patients, and each study demonstrated an effective reduction of low-density lipoprotein ranging from 40 to 87% decrease from baseline. In our study, the 110 patients from literature review were added to a cohort of 7 similar patients from our institution for combined analysis. This report supports that PCSK9 inhibitors should be considered following cardiac transplantation when conventional medial therapy is not tolerated or ineffective.


Spatiotemporal complexity patterns of resting-state bioelectrical activity explain fluid intelligence: Sex matters.
Neural complexity is thought to be associated with efficient information processing but the exact nature of this relation remains unclear. Here, the relationship of fluid intelligence (gf) with the resting-state EEG (rsEEG) complexity over different timescales and different electrodes was investigated. A 6-min rsEEG blocks of eyes open were analyzed. The results of 119 subjects (57 men, mean age = 22.85 ± 2.84 years) were examined using multivariate multiscale sample entropy (mMSE) that quantifies changes in information richness of rsEEG in multiple data channels at fine and coarse timescales. gf factor was extracted from six intelligence tests. Partial least square regression analysis revealed that mainly predictors of the rsEEG complexity at coarse timescales in the frontoparietal network (FPN) and the temporo-parietal complexities at fine timescales were relevant to higher gf. Sex differently affected the relationship between fluid intelligence and EEG complexity at rest. In men, gf was mainly positively related to the complexity at coarse timescales in the FPN. Furthermore, at fine and coarse timescales positive relations in the parietal region were revealed. In women, positive relations with gf were mostly observed for the overall and the coarse complexity in the FPN, whereas negative associations with gf were found for the complexity at fine timescales in the parietal and centro-temporal region. These outcomes indicate that two separate time pathways (corresponding to fine and coarse timescales) used to characterize rsEEG complexity (expressed by mMSE features) are beneficial for effective information processing.


Malnutrition-Inflammation Complex Syndrome and Bone Fractures and Cardiovascular Disease Events in Patients Undergoing Hemodialysis: The Q-Cohort Study.
Malnutrition-inflammation complex syndrome (MICS) is common in patients receiving hemodialysis and increases the risks of morbidity and mortality. However, few studies have examined the overall impact of MICS on disorders of the bone-cardiovascular axis. Prospective, multicenter, observational cohort study. A total of 3,030 patients receiving maintenance hemodialysis registered in the Q-Cohort Study. A newly developed score for MICS composed of elements chosen from 8 baseline parameters related to nutrition and inflammation by bootstrap resampling, multivariable-adjusted Cox proportional hazard risk analysis for all-cause mortality, and the risk prediction rule. β-coefficients of each element analyzed in the multivariable-adjusted model were used for the creation of the MICS score. Bone fractures, cardiovascular disease events, and the composite outcome of bone fractures and cardiovascular disease events. Cox proportional hazard regression and Fine-Gray proportional subdistribution hazards regression. During a median follow-up of 4 years, 140 patients developed bone fractures and 539 developed cardiovascular disease events. Age; serum levels of creatinine, albumin, and C-reactive protein; and body mass index were selected for the creation of the MICS score. The median (IQR) MICS score was 196 (181-212). The multivariable-adjusted Cox proportional hazard risk model and the competing risk model showed that a higher MICS score was incrementally associated with elevated risks of bone fractures, cardiovascular disease events, and the composite outcome; hazard risks (95% CIs) of fractures, cardiovascular disease events, and the composite outcome for each 10-point increase in the MICS score were 1.18 (1.01-1.38), 1.16 (1.07-1.26), and 1.15 (1.07-1.24), respectively. One-time measurement of the parameters used for the creation of the MICS score. Malnutrition and inflammation represented by the MICS score were associated with increased risks of bone-cardiovascular axis disorders in patients receiving maintenance hemodialysis.


Genetic Structure and Genetic Diversity of the Endemic Korean Aucha Perch, Coreoperca herzi (Centropomidae), in Korea.
The Korean endemic aucha perch, Coreoperca herzi, belongs to the family Centropomidae. Thus far, studies on C. herzi have focused on mitochondrial genomes, egg development, and early life history, while studies on their genetic diversity or genetic structure are lacking. We investigated these aspects in this study using mitochondrial DNA data. Haplotypes were divided into the Hangang River, Nakdonggang River, Geumgang River, and southwest region water system populations. A translocated population, the Yangyang Namdaechun Stream, was confirmed to have originated from the Hangang River water system population based on haplotype distribution and genetic structure results. The FST of the mitochondrial DNA indicated distinct genetic differentiation in the Hangang, Nakdonggang, Geumgang, and southwest regions. According to COI and analyses, the analysis of molecular variance revealed a higher variance in the four water system groups (98.41%) than in the southwest region water system versus the Hangang River water system (80.27%) groups. This study presents basic data for conservation by providing extensive information on the genetic diversity, genetic structure, and translocation population of C. herzi.


Lung immunoglobulin A immunity dysregulation in cystic fibrosis.
In cystic fibrosis (CF), recurrent infections suggest impaired mucosal immunity but whether production of secretory immunoglobulin A (S-IgA) is impaired remains elusive. S-IgA is generated following polymeric immunoglobulin receptor (pIgR)-mediated transepithelial transport of dimeric (d-)IgA and represents a major defence through neutralisation of inhaled pathogens like Pseudomonas aeruginosa (Pa). Human lung tissue (n = 74), human sputum (n = 118), primary human bronchial epithelial cells (HBEC) (cultured in air-liquid interface) (n = 19) and mouse lung tissue and bronchoalveolar lavage were studied for pIgR expression, IgA secretion and regulation. Increased epithelial pIgR immunostaining was observed in CF lung explants, associated with more IgA-producing plasma cells, sputum and serum IgA, especially Pa-specific IgA. In contrast, pIgR and IgA transport were downregulated in F508del mice, CFTR-inhibited HBEC, and CF HBEC. Moreover, the unfolded protein response (UPR) due to F508del mutation, inhibited IgA transport in Calu-3 cells. Conversely, pIgR expression and IgA secretion were strongly upregulated following Pa lung infection in control and F508del mice, through an inflammatory host response involving interleukin-17. A complex regulation of IgA secretion occurs in the CF lung, UPR induced by CFTR mutation/dysfunction inhibiting d-IgA transcytosis, and Pa infection unexpectedly unleashing this secretory defence mechanism. This work was supported by the Forton's grant of the King Baudouin's Foundation, Belgium, the Fondazione Ricerca Fibrosi Cistica, Italy, and the Fonds National de la Recherche Scientifique, Belgium.


Biophilic virtual reality on children's anxiety and pain during circumcision: A randomized controlled study.
The aim of this study was to evaluate the effects of the biophilic virtual reality (BVR) method on children's pain and anxiety undergoing circumcision. This randomized controlled study used a parallel trial design guided by the CONSORT checklist. A total of 106 children were included in the analysis. Intraoperative anxiety was assessed by using the simplified Chinese version of the modified Yale Preoperative Anxiety Scale (CmYPAS), Visual Analogue Scale (VAS), heart rate (HR), and Anxiety index (Ai). Intraoperative pain was assessed by using the Faces Pain Scale-Revised (FPS-R), and Pain index (Pi). The Pearson correlation analysis was used to analyze the relationship between Ai and the CmYPAS. The primary outcomes were CmYPAS, VAS, and FPS-R, which were analyzed using the Kruskal-Wallis test. Baseline variables were not significantly different between the BVR group (34 patients), the indoor virtual reality (IVR) group (36 patients), and the blank control group (36 patients). The CmYPAS scores during surgery were significantly lower in the BVR group and the IVR group versus the blank control group (25.0[22.9-29.2], 22.9[22.9-29.2], 33.3[33.3-38.5] respectively; P < 0.001). The VAS scores during surgery were significantly lower in the BVR group and the IVR group versus the blank control group (5.0[3.0-7.0], 3.0[2.0-5.0], 6.0[5.0-8.8] respectively; P < 0.001). The FPS-R scores during surgery were significantly lower in the BVR group and IVR group versus the blank control group (2.0[1.8-4.2], 3.0[2.0-4.8], 5.5[5.0-8.0], respectively; P < 0.001). At removal of the foreskin, Pi were significantly lower in the BVR group and IVR group versus the blank control group (6.9[4.1], 7.7[3.3], 9.8[6.2] respectively; P = 0.033). The Ai scores at each time point were significantly lower in the BVR group and IVR group versus the control (P = 0.015, P = 0.006 respectively). The correlation analysis of Ai (at removal of the foreskin) and CmYPAS scores in children showed that the Pearson correlation coefficient was 0.194 (P = 0.046). This is the first RCT to investigate the effects of BVR in children undergoing circumcision. This study demonstrates a reduction in pediatric intraoperative pain and anxiety with the use of virtual reality (VR). Intraoperative VR may be an effective noninvasive modality for reducing pain and anxiety during circumcision. Pi and Ai might be used to assess subjective pain and anxiety in patients.


Claudin 1 expression in basal-like breast cancer is related to patient age.
Defects in tight junctions, gate-keepers of the integrity of the epidermal barrier function, are known to contribute to cancer development. As such, enhancing our understanding of how the expression of proteins involved in these junctions is regulated in cancer, remains a priority. Although the expression of one of these proteins, claudin 1, is down regulated in most invasive human breast cancers (HBC), we have recently shown that high levels of claudin 1, characterized tumors belonging to the very aggressive basal-like breast cancer (BLBC) subtype. In these tumors, the claudin 1 protein, usually localized in the cell membrane, is often mislocalized to the cytoplasm. To examine the clinical relevance of this observation, we have generated and analyzed an invasive HBC tissue microarray consisting of 151 breast tumor samples; 79 of which presented a basal-like phenotype (i.e. ER-ve, PR-ve HER2-ve, CK5/6 or EGFR+ve). We also interrogated the outcome of claudin 1 knockdown in a human BLBC cell line, BT-20. Immunohistochemical analysis of this patient cohort revealed a significant association between high claudin 1 expression and BLBCs in women 55 years of age and older. Interestingly, no significant association was found between claudin 1 and nodal involvement, tumor grade or tumor size. Regression analysis however, showed a significant positive association between claudin 1 and claudin 4, even though claudin 4 did not significantly correlate with patient age. Claudin 1 knockdown in BT-20 cells resulted in decreased cell migration. It also significantly altered the expression of several genes involved in epithelial-mesenchymal-transition (EMT); in particular, SERPINE 1 (PAI1) and SSP1 (osteopontin), known to inhibit EMT and cancer cell migration. Conversely, genes known to maintain EMT through their interaction, SNAIL2, TCF4 and FOXC2 were significantly down regulated. The association of high claudin 1 protein levels observed in tumors derived from older women with BLBC, suggests that claudin 1 has the potential to serve as a marker which can identify a specific subgroup of patients within the BLBC subtype and thus, further contribute to the characterization of these ill-defined breast cancers. More importantly, our studies strongly suggest that claudin 1 directly participates in promoting breast cancer progression, possibly through the alteration of expression of EMT genes.


Ventilation-induced neutrophil infiltration and apoptosis depend on apoptosis signal-regulated kinase 1 pathway.
Positive pressure ventilation with large tidal volumes has been shown to cause release of cytokines, including macrophage inflammatory protein (MIP)-2, a functional equivalent of human interleukin-8, neutrophil infiltration, and apoptosis. The mechanisms regulating ventilation-induced cytokine production and lung cell death are unclear. Based on our previous in vitro and in vivo models of lung cell stretch, we hypothesized that high tidal volume ventilation-induced MIP-2 production, neutrophil infiltration, and apoptosis are dependent on the activation of apoptosis signal-regulated kinase 1 (ASK1), the upstream activator of c-Jun N-terminal kinase (JNK). : Prospective, controlled animal experiment. University research laboratory. Male C57BL/6 mice, weighting 20-25 g. C57BL/6 mice were exposed to high tidal volume (30 mL/kg) or low tidal volume (6 mL/kg) mechanical ventilation for 15 mins to 5 hrs. High tidal volume ventilation induced MIP-2 messenger RNA expression, MIP-2 protein production, neutrophil migration into the lung, airway epithelial cell apoptosis, and activation of ASK1, JNK, and activator protein (AP)-1 DNA binding in a dose-dependent and time-dependent manner. ASK1 inhibition with thioredoxin attenuated high tidal volume ventilation-induced MIP-2 messenger RNA expression, MIP-2 protein production, neutrophil migration into the lung, airway epithelial cell apoptosis, activation of JNK, and AP-1 DNA binding. Our data showed that high tidal volume ventilation-induced MIP-2 production, neutrophil sequestration, and apoptotic cell death were dependent, in part, on activation of the ASK1/JNK/AP-1 pathway.


Topographic distribution of neurofibrillary tangles and granulovacuolar degeneration in hippocampal cortex of aging and demented patients. A quantitative study.
Topographic analysis was performed of the distribution of Alzheimer's neurofibrillary tangles and the granulovacuolar degeneration of Simchowicz in the hippocampal cortex of patients with Alzheimer's dementia and mentally normal aged controls. A semiautomated scanning stage microscope was linked potentiometrically to an XY pen recorder in order to plot cytoarchitectonic "scattergrams" from the sequentially screened hippocampal formations. The density of both lesions per cubic mm of pyramidal cortex was quantified by measuring the area of each of six "zones", using a digitizer and programmable calculator. In elderly normal brains as well as those of Alzheimer's disease, the statistically most representative ranking order of predilection for neurofibrillary tangles (in decreasing severity) was: entorhinal cortex greater than subiculum greater than H1 greater than end-plate greater than presubiculum greater than H2. For granulovacuolar degeneration the best rank order was: subiculum greater than H1 greater than H2 greater than end-plate greater than entorhinal cortex greater than presubiculum. The notable similarities of both such orders of predilection to the well-recognized "selective vulnerability" of certain hippocampal neurones in clinical conditions of hypoxia, ischemia and epilepsy suggest some common, focally accentuated cytotoxic mechanism may underlie all these regional predispositions.


Genome size and GC content of myxomycetes.
More than 1272 myxomycetes species have been described, accounting for more than half of all Amoebozoa species. However, the genome size of only three myxomycetes species has been reported. Therefore, we used flow cytometry to present an extensive survey and a phylogeny-based analysis of genome size and GC content evolution in 144 myxomycetes species. The genome size of myxomycetes ranged from 18.7 Mb to 470.3 Mb, and the GC content ranged from 38.7% to 70.1%. Bright-spored clade showed larger genome sizes and more intra-order genome size variations than the dark-spored clade. GC content and genome size were positively correlated in both bright-spored and dark-spored clades, and spore size was positively correlated with genome size and GC content in the bright-spored clade. We provided the first genome size data set in Myxomycetes, and our results will provide helpful information for future Myxomycetes studies, such as genome sequencing.


Optimization of ultrasonic transducers.
The so-called KLM-model for ultrasonic transducers is employed to optimize transducer design. Some new performance characteristics are defined which change monotonically with design parameters. These characteristics are based on the area of the envelope of the echo waveform produced by the transducer and of the corresponding amplitude spectrum. The efficiency of the transducer is defined by the round trip energy factor. The performance characteristics are used in a composite performance measure, which is then employed as a criterion in the optimization procedure. Two transducers are investigated: for medical imaging purposes and for spectral analysis of clinical echograms. The influence of electrical matching, backing impedance, matching layer impedance, bond line thickness and series induction on the optimized transducers is investigated.


[Improving production and bioactivity of recombinant human disintegrin domain of ADAM15 (rhADAM15) in Escherichia coli].
To enhance the production and bioactivity of recombinant human disintegrin domain of ADAM15 (A Disintegrin and Metalloproteinase 15) (rhADAM15) in Escherichia coli. The expression host was chose and the recombinant expression plasmid pGEX-ADAM15 was constructed, based on analysis of the cDNA sequence of rhADAM15. (1) 298 mg/L GST (Glutathione-S-transferase)-ADAM15 and 42 mg/L rhADAM15 were achieved when choosing E. coli Rosetta (DE3) as the expression host that could supply additional tRNA for rare codons. (2) The GST-ADAM15 expression level increased to 326 mg/L after changing the rare codon GGA (Gly425) to GGC by PCR (Polymerase Chain Reaction)-based site-directed mutagenesis. (3) The rhADAM15 concentration increased to 57 mg/L by deleting the "Pro-Glu-Phe" at the GST-ADAM15 junction to improve the thrombin cleavage efficiency. (4) Finally, by combinational introduction of the favorable codons and suitably eliminating of certain amino acid sequence, rhADAM15 concentration reached the highest level (68 mg/L). The high expression of heterologous protein could be achieved by releasing rare codon usage and amino acids residues restriction.


Effects of administration of dopamine and L-DOPA to dogs on their plasma level of dopamine sulfate.
The effect of intravenous administration of dopamine (DA) or L-3,4-dihydroxyphenylalanine (L-DOPA), its immediate precursor, on the level of DA sulfate in dog plasma was examined, to clarify the source and physiological significance of DA sulfate which is present at high level in the plasma. After DA administration, the plasma level of free DA increased markedly, but the level of DA sulfate did not change. However, after administration of L-DOPA, the levels of both free DA and DA sulfate increased greatly. After a single injection of L-DOPA, increase in the level of free DA was transient, but that of DA sulfate persisted for a long time. These results suggest that some of the DA sulfate in dog plasma is formed from circulating L-DOPA, not from circulating DA, and that formation of DA conjugate may play a role in regulating the plasma level of free DA.


Establishment and validation of an AI-aid method in the diagnosis of myocardial perfusion imaging.
This study aimed to develop and validate an AI (artificial intelligence)-aid method in myocardial perfusion imaging (MPI) to differentiate ischemia in coronary artery disease. We retrospectively selected 599 patients who had received gated-MPI protocol. Images were acquired using hybrid SPECT-CT systems. A training set was used to train and develop the neural network and a validation set was used to test the predictive ability of the neural network. We used a learning technique named "YOLO" to carry out the training process. We compared the predictive accuracy of AI with that of physician interpreters (beginner, inexperienced, and experienced interpreters). Training performance showed that the accuracy ranged from 66.20% to 94.64%, the recall rate ranged from 76.96% to 98.76%, and the average precision ranged from 80.17% to 98.15%. In the ROC analysis of the validation set, the sensitivity range was 88.9 ~ 93.8%, the specificity range was 93.0 ~ 97.6%, and the AUC range was 94.1 ~ 96.1%. In the comparison between AI and different interpreters, AI outperformed the other interpreters (most P-value < 0.05). The AI system of our study showed excellent predictive accuracy in the diagnosis of MPI protocols, and therefore might be potentially helpful to aid radiologists in clinical practice and develop more sophisticated models.


Predicting the size of salt-containing aqueous Na-AOT reverse micellar water-in-oil microemulsions with consideration for specific ion effects.
Reverse micellar solutions are thermodynamically stable systems in which surfactant molecules surround water droplets within a continuous organic phase. Among their many applications, they can be used for the synthesis of nanoparticles of controlled agglomeration. Here, we consider the role specific ion effects play in reverse micelle size reduction. Dynamic light scattering measurements and the Gouy-Chapman electrical double layer model were combined to study water/AOT/isooctane reverse micellar systems (wo = 10). Linear relationships between the solvodynamic diameter (D) of reverse micelles containing various concentrations of FeSO4, Mg(NO3)2, CuCl2, Al(NO3)3, Fe(NO3)3, Y(NO3)3, NaBH4, ZrOCl2, and NH4OH, and their calculated Debye screening lengths, κ-1, were observed with decreasing D and increasing salt concentration (c). By comparing the linear fits for reverse micelle size as a function of c-1/2, we determined the size can be described as a function of the Debye screening length, cation valency (z), and specific anion hydrated radius (ran), where D = 3.1z κ-1 + bi, and bi is linearly related to ran. Our model accurately predicts reverse micelle sizes with the addition of monovalent, divalent, and trivalent salts for which the primary hydrolyzed cation species has a charge that is equal to the cation valency.


A description of teaching methods using an on-site instructor versus a distant site instructor to train laryngoscopy to medical students in Hanoi, Vietnam, from Omaha, Nebraska, by video communication.
This study demonstrated a method to train medical students at Hanoi Medical School in airway management from Omaha, Nebraska, using tele-mentoring techniques. Correct placement of the endotracheal tube was documented by tele-broncoscopy following intubation. This technology may increase medical training capabilities in remote or developing areas of the world. Medical care delivery could be performed using this technology by tele-mentoring a lesser trained medical provider at a distant site enabling them to accomplish complex medical tasks.


Pneumonia due to aspiration of povidine iodine after preoperative disinfection of the oral cavity.
Povidone-iodine (PI) is thought to be an effective disinfectant and safe for many surgeons. Aspiration pneumonia is usually caused by gastric contents, but if PI solution will be aspirated, pneumonia or other complications may occur. We present a case of pneumonia to aspiration of PI solution in a 91-year-old man patient who underwent oral-maxillofacial surgery. When surgeons used PI solution for disinfection into the oral cavity, the solution seems to be sinking gradually. The patient showed severe respiratory distress and developed hypoxia. There were much frothy fluids into a tracheal tube. We suctioned through the endotracheal tube and performed bronchoscopy, that revealed a redness which appeared associated to a chemical injury on the left trachea and bronchus. His condition was complicated by ARDS and DIC. Periodical bronchial suction and guideline-based treatments of ARDS were carried in ICU. He recovered without severe complication. Although PI solution for an oral disinfection is used routinely, all operators need to be aware of the risk for PI aspiration.


Variable and invariable DNA repeat characters revealed by taxonprint approach are useful for molecular systematics.
A specially optimized restriction analysis of highly repetitive DNA elements, called DNA taxonprint, was applied for phylogenetic study of primates and lizards. It was shown that electrophoretic bands of DNA repeats revealed by the taxonprint technique have valuable properties for molecular systematics. Approximately half of taxonprint bands (TB) are invariable and do not disappear from the genomes during evolution or change spontaneously. Presumably these invariable bands are restriction fragments of dispersed DNA repeats. Another group represents variable taxonprint bands that differ even between closely related species. These variable bands are probably represented by tandem DNA repeats and could be used as species-specific markers. It was shown that taxonprint bands are independent characters since the appearance of a new taxonprint band does not change the previous band pattern. Phylogenetic reconstruction carried out on taxonprint data demonstrated that this approach could be of general utility for molecular systematics and species identification.


Expression of SFT (stimulator of Fe transport) is enhanced by iron chelation in HeLa cells and by hemochromatosis in liver.
SFT (stimulator of Fe transport) is a novel transport protein that has been found to facilitate uptake of iron presented to cells as either Fe(II) or Fe(III). When HeLa cells are exposed to the iron chelator desferrioxamine, levels of SFT mRNA increase in an actinomycin D-sensitive manner. In contrast, cells exposed to high levels of iron down-regulate SFT expression in a time-dependent and reversible fashion. Thus, homeostatic regulation of SFT expression not only ensures that sufficient levels of iron are maintained but also limits excessive assimilation to prevent potentially harmful effects of this toxic metal. The unexpected observation that SFT transcript levels are up-regulated in hemochromatosis patients therefore suggests that enhanced SFT expression contributes to the etiology of this iron overload disorder.


[Laparoscopic rectal resection technique].
The quality of radical oncological operations for patients with rectal cancer determines the rate of local recurrence and long-term survival. Neoadjuvant chemoradiotherapy for locally advanced tumors, a standardized surgical procedure for rectal tumors less than 12 cm from the anus with total mesorectal excision (TME) and preservation of the autonomous nerve system for sexual and bladder function have significantly improved the oncological results and quality of life of patients. The TME procedure for rectal resection has been performed laparoscopically in Germany for almost 20 years; however, no reliable data are available on the frequency of laparoscopic procedures in rectal cancer patients in Germany. The rate of minimally invasive procedures is estimated to be less than 20 %. A prerequisite for using the laparoscopic approach is implicit adherence to the described standards of open surgery. Available data from prospective randomized trials, systematic reviews and meta-analyses indicate that in the early postoperative phase the generally well-known positive effects of the minimally invasive approach to the benefit of patients can be realized without any long-term negative impact on the oncological results; however, the results of many of these studies are difficult to interpret because it could not be confirmed whether the hospitals and surgeons involved had successfully completed the learning curve. In this article we would like to present our technique, which we have developed over the past 17 years in more than 1000 patients. Based on our experiences the laparoscopic approach can be highly recommended as a suitable alternative to the open procedure.


Enkephalin degrading enzymes in cerebrospinal fluid.
Enkephalins were rapidly degraded by specific enzyme systems in vivo. In cerebrospinal fluid (CSF), however, it has been undefined whether these enzyme systems existed. Our experiments showed enkephalins were hydrolyzed by the enzymatic activity in both CSF of human and monkey. The results by the thin layer chromatography and the high performance liquid chromatography revealed the reaction products of CSF and enkephalin were tyrosine, tyrosyl-glycine and tyrosyl-glycyl-glycine. Therefore, the enzymes in CSF were considered to be an aminopeptidase, a dipeptidyl aminopeptidase and a dipeptidyl carboxypeptidase. Our results suggest that in the assay of enkephalin in CSF, the effects of these enzymes should be considered.


An R2R3-MYB transcription factor, OjMYB1, functions in anthocyanin biosynthesis in Oenanthe javanica.
This study showed that an R2R3-MYB transcription factor, OjMYB1, is involved in anthocyanin biosynthesis and accumulation in Oenanthe javanica. Anthocyanins can be used as safe natural food colorants, obtained from many plants. R2R3-MYB transcription factors (TFs) play important roles in anthocyanins biosynthesis during plant development. Oenanthe javanica is a popular vegetable with high nutritional values and numerous medical functions. O. javanica has purple petioles that are mainly due to anthocyanins accumulation. In the present study, the gene encoding an R2R3-MYB TF, OjMYB1, was isolated from purple O. javanica. Sequencing results showed that OjMYB1 contained a 912-bp open reading frame encoding 303 amino acids. Sequence alignments revealed that OjMYB1 contained bHLH-interaction motif ([DE]Lx2[RK]x3Lx6Lx3R) and ANDV motif ([A/G]NDV). Phylogenetic analysis indicated that the OjMYB1 classified into the anthocyanins biosynthesis clade. Subcellular localization assay showed that OjMYB1 was a nuclear protein in vivo. The heterologous expression of OjMYB1 in Arabidopsis could enhance the anthocyanins content and up-regulate the expression levels of the structural genes-related anthocyanins biosynthesis. Yeast two-hybrid assay indicated that OjMYB1 could interact with AtTT8 and AtEGL3 proteins. Enzymatic analysis revealed that overexpression of OjMYB1 gene up-regulated the enzyme activity of 3-O-glycosyltransferase encoded by AtUGT78D2 in transgenic Arabidopsis. Our results provided a comprehensive understanding of the structure and function of OjMYB1 TF in O. javanica.


Solid phase chemical technologies for combinatorial chemistry.
This article describes the exploration of synthetic methodologies on solid phase for combinatorial chemistry. Examples will cover various cyclisation strategies that include; the intramolecular Heck cyclisation leading to the formation of oxindoles, the radical cyclisation mechanism in the synthesis of furans, and a stereoselective cyclisation to form oxopiperazines.


Neuroprotective potential of Myrica esulenta in Haloperidol induced Parkinson's disease.
Myrica esculenta is a notable therapeutic plant widely utilized in Indian system of medicine. Ayurvedic literature reported fruit and bark of this plant is used in gulma, jvara, arsa, grahani, pandu roga, hrillasa, mukha roga, kasa, svasa, agnimandhya, aruchi, meha, and kantharoga. The present study aimed to investigate the neuroprotective potential of "Himalayan Bayberry" (Myrica esculenta Buch.-Ham. ex D. Don) leaves methanol extract in Parkinson's disease induced by haloperidol. The present investigation was completed in wistar rats, in which Parkinson's disease (PD) was induced with haloperidol 1 mg/kg, intraperitoneally. The rats were randomly divided into six gatherings and the test animals received the methanolic extract of M. esculenta (MEME) at a dose of 50, 100 and 200 mg/kg, orally for one week. Various behavioural, biochemical and histopathological parameters were estimated in haloperidol exposed rats. MEME demonstrated significant and dose-dependent increment in behavioural activity and improved muscle coordination. The significant diminution in malonaldehyde level while improved the level of antioxidant enzymes like catalase, superoxide dismutase and reduced glutathione in extract treated group were observed as compared to the control group. Histopathological changes revealed MEME significantly reduced haloperidol-induced damage in the substantia nigra and there was very little neuronal atrophy. The outcomes showed the defensive role of M. esculenta against PD. The mechanism of protection may be due to an escalation of cellular antioxidants.


Expression of Multiple Functional RNAs or Proteins from One Viral Vector.
In this chapter, we will cover the available design choices for enabling expression of two functional protein or RNA sequences from a single viral vector. Such vectors are very useful in the neuroscience-related field of neuronal control and modulation, e.g., using optogenetics or DREADDs, but are also desirable in applications of CRISPR/Cas9 in situ genome editing and more refined therapeutic approaches. Each approach to achieving this combined expression has its own strengths and limitations, which makes them more or less suitable for different applications. In this chapter, we describe the available alternatives and provide tips on how they can be implemented.


The Structure of Sub-nm Platinum Clusters at Elevated Temperatures.
Little is known about metallic clusters consisting merely of a dozen of atoms or even less, despite of their importance in catalysis and crystal nucleation. Scanning transmission electron microscopy (STEM) provides direct atomic structure information but has inherently suffered from limited time resolution. We employ fast dynamic STEM combined with a spatio-temporal image denoising algorithm to explore the structure and stability of Pt clusters on carbon, which represents a highly relevant catalysis system. At room temperature, dynamic amorphous 2D structures are found, while above ≈300 °C, the clusters transform into a crystalline state. Our experimental and theoretical data reveal an unexpected strong trend of the crystalline clusters to exhibit the face-centered cubic, bulk structure of Pt with cuboidal geometries being most prominent.


Correction to: Adrenocortical incidentalomas and bone: from molecular insights to clinical perspectives.
The original version of this article unfortunately contained a mistake in Figure 1. There is a typo in the word "osteoclastogenesis" and the word "activity" is missing in the same entity. It should be "osteoclastogenesis" instead of "osteoclestogenesis".


Performance of bovine genital campylobacteriosis diagnostic tests in bulls from Uruguay: a Bayesian latent class model approach.
The sensitivity (Se) and specificity (Sp) of three diagnostic tests for the detection of Campylobacter fetus venerealis (Cfv) using field samples were estimated using a Bayesian latent class model (BLCM), accounting for the absence of a gold standard. The tests included in this study were direct immunofluorescence antibody test (IFAT), polymerase chain reaction (PCR), and real-time PCR (RT-PCR). Twelve farms from two different populations were selected and bull prepuce samples were collected. The IFAT was performed according to the OIE Manual. The conventional PCR was performed as multiplex, targeting the gene nahE for C. fetus species identification and insertion element ISCfe1 for Cfv identification. The RT-PCR was performed as uniplex: one targeting the gene nahE for C. fetus and the other targeting the insertion ISCfe1 (ISC2) for Cfv. Results from the BLCM showed a median Se of 11.7% (Bayesian credibility interval (BCI): 1.93-29.79%), 53.7% (BCI: 23.1-95.0%), and 36.1% (BCI: 14.5-71.7%) for IFAT, PCR, and RT-PCR respectively. The Sp were 94.5% (BCI: 90.1-97.9%), 97.0% (BCI: 92.9-99.3%), and 98.4% (BCI: 95.3-99.7%) for IFAT, PCR, and RT-PCR respectively. The correlation between PCR and RT-PCR was positive and low in samples from both sampled population (0.63% vs 8.47%). These results suggest that diagnostic sensitivity of the studied tests is lower using field samples than using pure Cfv strains.


Hepatitis B mother-to-child transmission in the Eastern Region of Ghana: a cross-sectional pilot study.
Hepatitis B is a major health concern in Ghana, where prevalence of the virus remains high and most chronic patients are infected during childhood or at birth. This study aimed to determine the prevalence and main factors associated with mother-to-child transmission of hepatitis B in the context of Ghana. In this cross-sectional pilot study, we tested infants born to hepatitis B positive mothers at a hospital in the Eastern Region of Ghana to determine the prevalence of mother-to-child transmission. A questionnaire was completed by hepatitis B positive mothers to investigate the association between factors surrounding the birth of the child and whether transmission had occurred. These factors were analyzed independently using Fisher's exact test. To investigate the relationship between mother's age at the time of delivery and viral transmission, a univariate logistic regression analysis was performed. The prevalence of mother-to-child transmission was 5.9%, with 51 hepatitis B positive mothers included in the study and three infants testing positive. A majority of infants received the standard hepatitis B vaccination schedule (96.1%) while two-thirds received the birth dose. There was no significant association observed between the clinical interventions reported in the study and mother-to-child transmission. No significant association was observed between the age of the mother at the time of delivery and viral transmission (OR: 1.077, 95% CI: 0.828 - 1.403, p = 0.58). Viral marker testing during pregnancy was absent in the population and could not be reliably assessed. There was a low prevalence of HBV mother-to-child transmission observed despite a clear absence of viral marker and viral load testing. It is recommended that viral profile analysis is performed for hepatitis B positive pregnancies to identify high risk cases.


[Thermovibrotherapy in the combined rehabilitation of children with a history of acute pneumonia].
A clinical response and the effect on local bronchopulmonary immunity have been assessed for thermotherapy and vibrotherapeutics used in convalescent young children who had acute pneumonia. The clinical and immunological appearance of the children was found to improve due to combined rehabilitation measures involving thermovibrotherapy.


Left Lateralization of the Cortical Auditory-Evoked Potential Reflects Aided Processing and Speech-in-Noise Performance of Older Listeners With a Hearing Loss.
We analyzed the lateralization of the cortical auditory-evoked potential recorded previously from aided hearing-impaired listeners as part of a study on noise-mitigating hearing aid technologies. Specifically, we asked whether the degree of leftward lateralization in the magnitudes and latencies of these components was reduced by noise and, conversely, enhanced/restored by hearing aid technology. We further explored if individual differences in lateralization could predict speech-in-noise abilities in listeners when tested in the aided mode. The study followed a double-blind within-subjects design. Nineteen older adults (8 females; mean age = 73.6 years, range = 56 to 86 years) with moderate to severe hearing loss participated. The cortical auditory-evoked potential was measured over 400 presentations of a synthetic /da/ stimulus which was delivered binaurally in a simulated aided mode using shielded ear-insert transducers. Sequences of the /da/ syllable were presented from the front at 75 dB SPL-C with continuous speech-shaped noise presented from the back at signal-to-noise ratios of 0, 5, and 10 dB. Four hearing aid conditions were tested: (1) omnidirectional microphone (OM) with noise reduction (NR) disabled, (2) OM with NR enabled, (3) directional microphone (DM) with NR disabled, and (4) DM with NR enabled. Lateralization of the P1 component and N1P2 complex was quantified across electrodes spanning the mid-coronal plane. Subsequently, listener speech-in-noise performance was assessed using the Repeat-Recall Test at the same signal-to-noise ratios and hearing aid conditions used to measure cortical activity. As expected, both the P1 component and the N1P2 complex were of greater magnitude in electrodes over the left compared to the right hemisphere. In addition, N1 and P2 peaks tended to occur earlier over the left hemisphere, although the effect was mediated by an interaction of signal-to-noise ratio and hearing aid technology. At a group level, degrees of lateralization for the P1 component and the N1P2 complex were enhanced in the DM relative to the OM mode. Moreover, linear mixed-effects models suggested that the degree of leftward lateralization in the N1P2 complex, but not the P1 component, accounted for a significant portion of variability in speech-in-noise performance that was not related to age, hearing loss, hearing aid processing, or signal-to-noise ratio. A robust leftward lateralization of cortical potentials was observed in older listeners when tested in the aided mode. Moreover, the degree of lateralization was enhanced by hearing aid technologies that improve the signal-to-noise ratio for speech. Accounting for the effects of signal-to-noise ratio, hearing aid technology, semantic context, and audiometric thresholds, individual differences in left-lateralized speech-evoked cortical activity were found to predict listeners' speech-in-noise abilities. Quantifying cortical auditory-evoked potential component lateralization may then be useful for profiling listeners' likelihood of communication success following clinical amplification.