Airway dimensional changes following bone anchored maxillary protraction: a systematic review.
The introduction of skeletal anchorage utilized for maxillary protraction with a face mask or class III elastics has been developed for the management of class III malocclusions with minimal dental effect. The objective of the present review was to evaluate the current evidence regarding airway dimensional changes following bone-anchored maxillary protraction. A search was conducted by two authors (S.A & B.A) in the following databases: MEDLINE via PubMed, Cochrane Library, Web of Science, Scopus, Google Scholar and Open Grey; besides a hand search in references of selected articles and developing a search alert in electronic databases. Selection criteria comprised randomized as well as prospective clinical trials evaluating airway dimensional changes following bone-anchored maxillary protraction. Relevant data were extracted after studies retrieval and selection. The risk of bias was thereafter evaluated using the revised RoB 2 tool for randomized clinical trials and the ROBINS-I tool was used for non-randomized clinical trials. The quality of studies was assessed using the modified Jadad score. After examining (eligibility) full-text articles, four clinical trials were ultimately included. These studies evaluated the airway dimensional changes, following bone-anchored maxillary protraction in comparison to different control study groups. Based on the available evidence, all the bone-anchored maxillary protraction devices used in the eligible studies in the present systematic review resulted in an improvement in the airway dimensions. However, due to the few numbers of studies available and the guarded evidence due to the low quality of evidence of three out of four included articles, there is no strong evidence to support a significant increase in the airway dimensions following bone-anchored maxillary protraction. Therefore, there is a need for more randomized controlled clinical trials with similar bone-anchored protraction devices and similar assessment methods for more valid comparisons, excluding any confounding factors, on airway dimensional changes.


Femtosecond Exciton Relaxation in Chlorosomes of the Photosynthetic Green Bacterium Chloroflexus aurantiacus.
Process of photosynthesis in the green bacteria Chloroflexus (Cfx.) aurantiacus starts from absorption of light by chlorosomes, peripheral antennas consisting of thousands of bacteriochlorophyll c (BChl c) molecules combined into oligomeric structures. In this case, the excited states are formed in BChl c, energy of which migrates along the chlorosome towards the baseplate and further to the reaction center, where the primary charge separation occurs. Energy migration is accompanied by non-radiative electronic transitions between the numerous exciton states, that is, exciton relaxation. In this work, we studied dynamics of the exciton relaxation in Cfx. aurantiacus chlorosomes using differential femtosecond spectroscopy at cryogenic temperature (80 K). Chlorosomes were excited by 20-fs light pulses at wavelengths in the range from 660 to 750 nm, and differential (light-dark) absorption kinetics were measured at a wavelength of 755 nm. Mathematical analysis of the obtained data revealed kinetic components with characteristic times of 140, 220, and 320 fs, which are responsible for exciton relaxation. As the excitation wavelength decreased, the number and relative contribution of these components increased. Theoretical modelling of the obtained data was carried out based of the cylindrical model of BChl c. Nonradiative transitions between the groups of exciton bands were described by a system of kinetic equations. The model that takes into account energy and structural disorder of chlorosomes turned out to be the most adequate.


Extracellular matrix for repair of type IV laryngotracheo-esophageal cleft.
Type IV laryngotracheo-esophageal cleft (LTEC) extending to the level of the carina presents unique challenges to operative repair, particularly with respect to soft tissue durability. This is the first report of CorMatrix(®) extra-cellular matrix (ECM) material use as an interposition graft in a four-layered LTEC repair. At day seven post-operatively, there was epithelialization along the surface of the trachea. At 3 months, she was stable for tracheotomy. At 6 months, the posterior wall resembled completely native tissue. CorMatrix(®) ECM(®) use intra-operatively and post-operative outcome were both highly satisfactory. No adverse reaction was seen in this case through 12-month follow up.


Comparison of Value at Risk (VaR) Multivariate Forecast Models.
We investigate the performance of VaR (Value at Risk) forecasts, considering different multivariate models: HS (Historical Simulation), DCC-GARCH (Dynamic Conditional Correlation-Generalized Autoregressive Conditional Heteroskedasticity) with normal and Student's t distribution, GO-GARCH (Generalized Orthogonal-Generalized Autoregressive Conditional Heteroskedasticity), and copulas Vine (C-Vine, D-Vine, and R-Vine). For copula models, we consider that marginal distribution follow normal, Student's t and skewed Student's t distribution. We assessed the performance of the models using stocks belonging to the Ibovespa index during the period from January 2012 to April 2022. We build portfolios with 6 and 12 stocks considering two strategies to form the portfolio weights. We use a rolling estimation window of 500 and 1000 observations and 1%, 2.5%, and 5% as significance levels for the risk estimation. To evaluate the quality of the risk forecasts, we compute the realized loss and cost. Our results show that the performance of the models is sensitive to the use of different significance levels, rolling windows, and strategies to determine portfolio weights. Furthermore, we find that the model that presents the best trade-off between the costs from risk overestimation and underestimation does not coincide with the model suggested by the realized loss.


Aflatoxin contamination of rice in the United Arab Emirates.
Many people in the United Arab Emirates store rice in large quantities for long periods of time before use. Five hundred samples of rice were collected from households in Al-Ain city during the summers of 1992-1994. Aflatoxin B1 was detected in 160 samples (64%) of long grain rice and 81 Samples (32%) of short grain rice at levels ranging from 1.2 to 16.5 µg/kg. The moisture content of samples varied between 5.7% and 15.3%. Species ofAspergillus andPenicillium (includingA. flavus andA. parasiticus) were isolated from discoloured, broken and insect damaged grain and it was confirmed that at least two of the isolates ofA. flavus were aflatoxigenic. These findings demonstrate that rice may contribute to dietary exposure to aflatoxins which are known to be carcinogenic and immunosuppressive.


Gene targeting and cloning in pigs using fetal liver derived cells.
Since there are no pig embryonic stem cells, pig genetic engineering is done in fetal fibroblasts that remain totipotent for only 3 to 5 wk. Nuclear donor cells that remain totipotent for longer periods of time would facilitate complicated genetic engineering in pigs. The goal of this study was to test the feasibility of using fetal liver-derived cells (FLDC) to perform gene targeting, and create a genetic knockout pig. FLDC were isolated and processed using a human liver stem cell protocol. Single copy α-1,3-galactosyl transferase knockout (GTKO) FLDCs were created using electroporation and neomycin resistant colonies were screened using PCR. Homozygous GTKO cells were created through loss of heterozygosity mutations in single GTKO FLDCs. Double GTKO FLDCs were used in somatic cell nuclear transfer (SCNT) to create GTKO pigs. FLDCs grew for more than 80 population doublings, maintaining normal karyotype. Gene targeting and loss of heterozygosity mutations produced homozygous GTKO FLDCs. FLDCs used in SCNT gave rise to homozygous GTKO pigs. FDLCs can be used in gene targeting and SCNT to produce genetically modified pigs. The increased life span in culture compared to fetal fibroblasts may facilitate genetic engineering in the pig.


Wilms tumor genes.
Multiple 'WT' genes exist. The WT1 gene at chromosomal band 11p13 has been cloned and is known to be important in the etiology of at least some tumors by virtue of the identification of both germline and somatic mutations in WT patients. Genes at 11p15 and 16q are also involved, either as initiating or tumor progression events. An unlocalized familial predisposition gene is also known to be important etiologically. The identification of several genes that are involved in the etiology or progression of WT, the preferential loss of maternally derived alleles in tumor tissue, and the observed reduction to 11p homozygosity in normal tissue DNA from some patients, all strikingly indicate that a simple, one-locus-'two-hit' genetic model for WT is inadequate. The question is not if this model needs to be modified, but how it should be modified, or if it is even valid enough to be a starting point for understanding the genetics of Wilms tumor. To begin to address this, several questions can be asked. Do all Wilms tumors carry mutations at the WT1 locus? Do both alleles at the WT1 locus need to be inactivated or lost for tumorigenesis? Or, instead, do some WT1 mutations act dominantly? Do patients with bilateral disease carry germline mutations as originally hypothesized, or, as more recently suggested, is bilateral disease the result of early somatic mutations, genomic imprinting, or multifactorial inheritance? Must mutations at an 11p15 locus and/or 11p15 LOH accompany WT1 mutations, or do 11p13 and 11p15 mutations act independently of each other? Have tumors from familial WT cases (who do not carry germline WT1 mutations) sustained somatic mutations at the WT1 locus, the 11p15 locus or the 16q locus? Conversely, do tumors from sporadic WT patients carry somatic mutations at the non-11p familial predisposition gene? Will most tumors be found to carry mutations at the same one or two loci, but differ only with regard to whether the mutations are somatic or germline? Are effects of genomic imprinting layered over, so to speak, a framework of classically mendelian mutations, or in some cases is imprinting the mechanism by which genes are inactivated or their normal function modulated? Although not definitive, there are data that bear on some of these questions. Germline mutations have been observed in patients with bilateral tumors, but may not prove to be a universal feature of bilateral disease.(ABSTRACT TRUNCATED AT 400 WORDS)


Studies on Some New Ru(III) Complexes Using aryl-azo Pentane- 2,4-dione and 2,6-bis (2'-Benzimidazolyl) Pyridine as Ligands: Synthesis, Spectroscopic, Luminescent, Electrochemical and Biological Activities.
Some ruthenium(III) complexes with aryl-azo 2,4-pentanedione as co-ligands (L(1)H - L(3)H(2)) have been synthesized and characterized spectroscopically IR, (1)H NMR, UV/Vis, ESR, conductimetric) along with elemental analysis and FAB-mass data. Their luminescent and redox properties have been studied. The antibacterial, anti-HIV and antitmnour activities have also been reported.


Does the choice of syndesmotic screw versus suture button in ankle surgery has a silver lining? - a technical note.
Unstable ankle fractures with associated syndesmotic injury are of considerable morbidity in the professional athlete population. The use of dynamic suture button versus static syndesmotic screws fixation, rehabilitation protocols and timing to return to play are still areas of debate. We report the use of novel algorithm of sequential static and dynamic syndesmotic fixation in an elite football player with Weber C ankle fracture. The patient underwent open reduction and internal fixation for a weber C ankle fracture with associated syndesmotic and deltoid ligament injury. The osteosynthesis included lateral malleolus neutralizing plate, two syndesmotic screws and deltoid anchor repair. At 6 weeks post-operative both syndesmotic screws were removed and one suture button was implanted in the proximal screw hole. After the second operation the patient was allowed full weight bearing and range of motion in all direction with accelerated rehabilitation protocol. The technique provided satisfactory results. At 4 month the player participated in a 90 min official football match. The fracture healed uneventfully with no recurrent syndesmotic diastasis. The presented technique of sequential dynamic and static fixation of associated syndesmotic injuries combined advantages of both syndesmotic screws and suture button implants. In an aim to allow earlier return to play in an elite football player. This opens the way for higher level of evidence clinical trials.


Estimation of the useful lifetime of polypropylene fiber in the anterior chamber.
A study of the stability of polypropylene fiber, size 4-0, to ultraviolet light was performed. Samples were radiated in physiological saline solution at 35.5 +/- 1.5 degrees C using a xenon-arc lamp at an intensity of 650 milliwatts per square centimeter. The light was filtered to remove wavelengths below 300 nanometers and thus simulated transmittance of the cornea. Tensile strength, elongation and modulus, and the surface morphology of the fiber by scanning electron microscopy (SEM) were determined as a function of exposure time. The average ultraviolet (UV) light intensity which irradiates the eye was determined from available meteorological data and was used to calculate human exposure at various geographical locations. This information along with the light energy of the xenon-arc lamp was used to calculate the useful lifetime of polypropylene fiber in the anterior chamber. Using an average exposure of 2.2 hours per day for a 60-year-old implant recipient, the useful lifetime ranges from 53 years in Miami, Florida, to 75 years in Seattle, Washington. Polypropylene loops from lenses which had been implanted in human eyes for up to 4.8 years showed no molecular degradation as compared to control material. Polypropylene fiber is therefore safe for use in anterior chamber implants.


Review of the Chinese medical approach to the management of fibromyalgia.
Traditional Chinese medicine (TCM) has a long history of efficacy in treating chronic illness. TCM views fibromyalgia and related conditions as disorders in the movement of energy (Qi) and body fluids (including blood) in the body and gets excellent treatment results using acupuncture, herbal medicine, massage, diet, and exercise to restore the proper flow of Qi and fluids. This article briefly introduces the TCM model of human physiology and TCM diagnostics and describes the TCM pathophysiology and treatment models for fibromyalgia.


Capillary electrochromatographic separation of enantiomers under aqueous mobile phases on a covalently bonded cellulose derivative chiral stationary phase.
A chemically bonded cellulose tris(3,5-dimethylphenylcarbamate) chiral stationary phase (CSP) was prepared by a radical polymerization reaction. The prepared CSP was packed into fused-silica capillaries with inner diameter of 75 microm to perform enantiomer separations in CEC. The electrochromatographic behavior of the CSP was investigated. On the prepared CSP, high EOF could be generated under acidic mobile phases, which represented an advantage for the separation of acidic enantiomers. Several neutral, acidic, and basic enantiomers were resolved on the prepared CSP under aqueous mobile phases. The column efficiencies were between 20,000 and 100,000 plates/m, which were much higher than those of HPLC. In addition, it was observed that the separation of some enantiomers benefited from the adoption of THF as mobile phase modifier.


Complete genome sequence of Paenibacillus xylanexedens PAMC 22703, a xylan-degrading bacterium.
Paenibacillus is widely distributed in various environments and has the potential for use as a biotechnological agent in industrial processes. Here, we report the complete genome sequence of the marine bacterium, Paenibacillus xylanexedens PAMC 22703, which utilizes xylan. The P. xylanexedens PAMC 22703 strain was isolated from marine sediments. P. xylanexedens PAMC 22703 utilizes xylan as a carbon source to grow. The genome sequence clarified that this strain possesses genes for utilizing xylan. The complete genome sequence contained one chromosome (7,053,622 bp with 46.0% GC content) and one plasmid (44,617 bp with 44.1% C + G content). The genome harbored genes that fully deploy the xylan assimilation pathway. The complete genome sequence of P. xylanexedens PAMC 22703 would prove useful in acquiring information for its application with xylan in various industries.


Formation of sarcomeres in the embryonic heart of the lobster.
Cardiomyoblasts in the myocardium of embryonic lobsters at 3-4 weeks and 6 months of development were examined with the transmission electron microscope in order to describe the events in the formation of sarcomeres in a neurogenic cardiac system. Thick and thin myofilaments appear first in the cell periphery near the sarcolemma. They align in parallel in a sequential fashion to form consecutive sarcomeric units. Well-defined A and I bands appear before any semblance of a Z line is present. The initial sarcomere is anchored to the sarcolemma by the insertion of thin myofilaments into a region of electron dense material associated intimately with the sarcolemma. Myofibrils grow outward in several planes away from the electron-dense regions of membrane that serve as focal points for myofibril formation.


The crystal structure of the cysteine protease Xylellain from Xylella fastidiosa reveals an intriguing activation mechanism.
Xylella fastidiosa is responsible for a wide range of economically important plant diseases. We report here the crystal structure and kinetic data of Xylellain, the first cysteine protease characterized from the genome of the pathogenic X. fastidiosa strain 9a5c. Xylellain has a papain-family fold, and part of the N-terminal sequence blocks the enzyme active site, thereby mediating protein activity. One novel feature identified in the structure is the presence of a ribonucleotide bound outside the active site. We show that this ribonucleotide plays an important regulatory role in Xylellain enzyme kinetics, possibly functioning as a physiological mediator.


Probing Vulnerability of the gp41 C-Terminal Heptad Repeat as Target for Miniprotein HIV Inhibitors.
One of the therapeutic strategies in HIV neutralization is blocking membrane fusion. In this process, tight interaction between the N-terminal and C-terminal heptad-repeat (NHR and CHR) regions of gp41 is essential to promote membranes apposition and merging. We have previously developed single-chain proteins (named covNHR) that accurately mimic the complete gp41 NHR region in its trimeric conformation. They tightly bind CHR-derived peptides and show a potent and broad HIV inhibitory activity in vitro. However, the extremely high binding affinity (sub-picomolar) is not in consonance with their inhibitory activity (nanomolar), likely due to partial or temporal accessibility of their target in the virus. Here, we have designed and characterized two single-chain covNHR miniproteins each encompassing one of the two halves of the NHR region and containing two of the four sub-pockets of the NHR crevice. The two miniproteins fold as trimeric helical bundles as expected but while the C-terminal covNHR (covNHR-C) miniprotein is highly stable, the N-terminal counterpart (covNHR-N) shows only marginal stability that could be improved by engineering an internal disulfide bond. Both miniproteins bind their respective complementary CHR peptides with moderate (micromolar) affinity. Moreover, the covNHR-N miniproteins can access their target in the context of trimeric native envelope proteins and show significant inhibitory activity for several HIV pseudoviruses. In contrast, covNHR-C cannot bind its target sequence and neither inhibits HIV, indicating a higher vulnerability of C-terminal part of CHR. These results may guide the development of novel HIV inhibitors targeting the gp41 CHR region.


Automated, portable, and high-throughput fluorescence analyzer (APHF-analyzer) and lateral flow strip based on CRISPR/Cas13a for sensitive and visual detection of SARS-CoV-2.
COVID-19 has erupted and quickly swept across the globe, causing huge losses to human health and wealth. It is of great value to develop a quick, accurate, visual, and high-throughput detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we developed a biosensor based on CRISPR/Cas13a combined with recombinase polymerase amplification (RPA) to detect S and Orf1ab genes of SARS-CoV-2 within 30 min. Most important of all, we developed an automated, portable, and high-throughput fluorescence analyzer (APHF-analyzer) with a 3D-printed microfluidic chip for sensitively detecting SARS-CoV-2, which addressed aerosol contamination issue and provided a more accurate and high-throughput detection during the on-site detection process. The detection limits of S gene and Orf1ab gene were as low as 0.68 fM and 4.16 fM. Furthermore, we used the lateral flow strip to realize visualization and point of care testing (POCT) of SARS-CoV-2. Therefore, profit from the efficient amplification of RPA and the high specificity of CRISPR/Cas13a, APHF-analyzer and the lateral flow strip to simultaneous detection of S gene and Orf1ab gene would be applied as a promising tool in the field of SARS-CoV-2 detection.


Genetic control of nucleoside transport in sheep erythrocytes.
Nucleoside transport in sheep erythrocytes is under the genetic control of two allelomorphic genes (NuI and Nui), where NuI codes for the functional absence of a high-affinity nucleoside transport system and is dominant to the gene (Nui) coding for the presence of the transport system. Kinetic and inhibitor experiments show that the high-affinity transport system is not present in heterozygous erythrocytes, demonstrating that the NuI gene is completely dominant over the Nui gene. It is suggested that the Nu locus may not represent the structural gene locus of the nucleoside transport system. Instead, it may be a regulator gene locus.


Differential diagnosis of fugue-like states.
Fugue-like states, though usually considered hysterical or epileptic in origin, can occur with many other psychiatric and neurologic conditions. The survey of literature should help the clinician with differential diagnosis. Nine illustrative cases are described and guidelines for investigating a case of fugue are outlined.


Metabolic burden in recombinant CHO cells: effect ofdhfr gene amplification andlacZ expression.
Foreign protein production levels in two recombinant Chinese hamster ovary (CHO) cell lines were compared in cells transfected with different expression vectors. One vector pNL1 contained the gene for neomycin resistance (neo ( r )) and thelacZ gene which codes for intracellular β-galactosidase, with both genes controlled by the constitutive simian virus (SV40) promoter. The other vector CDβG contained the amplifiabledhfr gene andlacZ gene, controlled by the constitutive SV40 and cytomegalovirus (CMV) promoters, respectively. Cell growth and β-galactosidase expression were compared quantitatively after cells were selected in different concentrations of the neomycin analog G418 and methotrexate, respectively. A 62% reduction in growth rate occurred in recombinant CHO cells in which thelacZ anddhfr genes were highly amplified and expressed. In contrast, the combined effects of the unamplifiedneo ( r ) gene andlacZ gene expression on the growth kinetics were small. Any metabolic burden caused bylacZ gene expression, which was evaluated separately from the effect ofneo ( r ) gene expression, must be negligible, as higher expression of β-galactosidase (1.5×10(-6) units/cell) occurred in unamplified cells compared to the cells in whichlacZ was amplified by thedhfr-containing vector (3×10(-7) units/cell). Thus, the main factor causing severe growth reduction ("metabolic burden") in cells containing the amplifieddhfr gene system was not overexpression of β-galactosidase butdhfr andlacZ gene co-amplification anddhfr gene expression.


Hemiparetic forms of cerebral palsy in relation to epilepsy and mental retardation.
Fifty-one children with hemiparetic cerebral palsy underwent clinical, EEG and CT examinations to assess mental performance, laterality of CP and incidence of epilepsy, 80 per cent of the children had epileptic abnormalities on EEG, but less than half had clinical signs of epilepsy. Clinical paroxysms were more frequent in those with right-sided hemiparesis. Focal or epileptic EEG changes were usual in those with right-hemisphere involvement, but unless clinical paroxysms developed, these had no bearing on mental performance. Lower IQ was found in the patients with clinical epilepsy--in nearly all cases with left-sided hemiparesis and in half of those with right-sided hemiparesis.


Retracted: Effects of the Ultrasound-Guided Stellate Ganglion Block on Hemodynamics, Stress Response, and Gastrointestinal Function in Postoperative Patients with Colorectal Cancer.
[This retracts the article DOI: 10.1155/2022/2056969.].


Blood Circulating Non-Coding RNAs for the Clinical Management of Triple-Negative Breast Cancer.
Triple negative breast cancer (TNBC) represents the most aggressive subtype of breast cancer, and is related to unfavorable prognosis and limited treatment strategies. Currently, there is a lack of reliable biomarkers allowing for the clinical management of TNBC. This is probably caused by a complex molecular background, leading to the development and establishment of a unique tumor phenotype. Recent studies have reported non-coding RNAs (ncRNAs) not only as the most promising class of molecular agents with a high applicability to manage human cancers, including TNBC, but also as robust and non-invasive biomarkers that are able to be monitored in blood circulation, with the application of liquid biopsy. There is a lack of papers discussing the role of blood-circulating ncRNAs as diagnostic, predictive, and prognostic biomarkers for TNBC. In this paper, we summarized the available literature reports on the utility of blood-circulating ncRNAs for TNBC management. Additionally, we supplemented this review by bioinformatics analysis, for better understanding of the role of ncRNAs' machinery in the development of a unique TNBC phenotype.


Role of Bioinformatics in the Study of Ionic Channels.
Ionic channels belong to the group of the most important proteins. Not only do they enable transmembrane transport but they are also the key factors for proper cell function. Mutations changing their structure and functionality often lead to severe diseases called channelopathies. On the other hand, transmembrane channels are very difficult objects for experimental studies. Only 2% of experimentally identified structures are transmembrane proteins, while genomic studies show that transmembrane proteins make up 30% of all coded proteins. This gap could be diminished by bioinformatical methods which enable modeling unknown protein structures, functions, transmembrane location, and ligand binding. Several in silico methods dedicated to transmembrane proteins have been developed; some general methods could also be used. They provide the information unavailable from experiments. Current modeling tools use a variety of computational methods, which provide results of surprisingly high quality.


Plaque Composition as a Predictor of Plaque Ulceration in Carotid Artery Atherosclerosis: The Plaque At RISK Study.
Plaque ulceration is a marker of previous plaque rupture. We studied the association between atherosclerotic plaque composition at baseline and plaque ulceration at baseline and follow-up. We included symptomatic patients with a carotid stenosis of <70% who underwent MDCTA and MR imaging at baseline (n = 180). MDCTA was repeated at 2 years (n = 73). We assessed the presence of ulceration using MDCTA. Baseline MR imaging was used to assess the vessel wall volume and the presence and volume of plaque components (intraplaque hemorrhage, lipid-rich necrotic core, and calcifications) and the fibrous cap status. Associations at baseline were evaluated with binary logistic regression and reported with an OR and its 95% CI. Simple statistical testing was performed in the follow-up analysis. At baseline, the prevalence of plaque ulceration was 27% (49/180). Increased wall volume (OR = 12.1; 95% CI, 3.5-42.0), higher relative lipid-rich necrotic core (OR = 1.7; 95% CI, 1.3-2.2), higher relative intraplaque hemorrhage volume (OR = 1.7; 95% CI, 1.3-2.2), and a thin-or-ruptured fibrous cap (OR = 3.4; 95% CI, 1.7-6.7) were associated with the presence of ulcerations at baseline. In 8% (6/73) of the patients, a new ulcer developed. Plaques with a new ulceration at follow-up had at baseline a larger wall volume (1.04 cm3 [IQR, 0.97-1.16 cm3] versus 0.86 cm3 [IQR, 0.73-1.00 cm3]; P = .029), a larger relative lipid-rich necrotic core volume (23% [IQR, 13-31%] versus 2% [IQR, 0-14%]; P = .002), and a larger relative intraplaque hemorrhage volume (14% [IQR, 8-24%] versus 0% [IQR, 0-5%]; P < .001). Large atherosclerotic plaques and plaques with intraplaque hemorrhage and lipid-rich necrotic cores were associated with plaque ulcerations at baseline and follow-up.


Cerebrovascular Doppler examination and cerebral angiography--alternative or complementary?
Obstructions in the extracranial cerebral arteries can be detected noninvasively by directional Doppler ultrasound technique using 'indirect' and 'direct' criteria. The indirect criteria are based on measurement of flow in the common carotid and in the terminal branches of the ophthalmic artery before and after the common carotid artery and branches of the external carotid artery are compressed. With the direct criteria, internal and external carotid artery are differentiated by diastolic flow, and local inhomogenetics of flow (turbulence) are detected. Flow in the vertebral artery is picked up transorally in the oropharynx. The Doppler examination was used in 2230 patients of whom 436 underwent angiography. The results of Doppler and angiography correlated in more than 90% of the cases.


The impact of repeated bladder surgery on successful bladder neck closure in classic bladder exstrophy: The role of mucosal violations.
Restoration of genitourinary anatomy with functional urinary continence is the reconstruction aim is the exstrophy-epispadias complex (EEC). In patients who do not achieve urinary continence or those who are not a candidate for bladder neck reconstruction (BNR), bladder neck closure (BNC) is considered. Interposing layers including human acellular dermis (HAD) and pedicled adipose tissue are routinely placed between the transected bladder neck and distal urethral stump to reinforce the BNC and minimize failure due to fistula development from the bladder. The aim of this study was to review classic bladder exstrophy (CBE) patients who underwent BNC to identify predictors of BNC failure. Specifically, we hypothesize that increased operations on the bladder urothelium leads to a higher rate of urinary fistula. CBE patients who underwent BNC were reviewed for predictors of failed BNC which was defined as bladder fistula development. Predictors included prior osteotomy, interposing tissue layer use and number of previous bladder mucosal violations (MV). A MV was defined as a procedure when the bladder mucosa was opened or closed for: exstrophy closure(s), BNR, augmentation cystoplasty or ureteral re-implantation. Predictors were evaluated using multivariate logistic regression. A total of 192 patients underwent BNC of which 23 failed. Patients were more likely to develop a fistula with a wider pubic diastasis at time of primary exstrophy closure (4.4 vs 4.0 cm, p=0.0016), have failed exstrophy closure (p=0.0084), or have 3 or more MVs before BNC (p=0.0002). Kaplan-Meier analysis of fistula-free survival after BNC, demonstrated an increased fistula rate with additional MVs (p=0.0004, Figure 1). MVs remained significant on multivariate logistic regression analysis with a per-violation odds ratio of 5.1 (p<0.0001). Of the 23 failed BNC's, 16 were surgically closed including 9 using a pedicled rectus abdominis muscle flap which was secured to the bladder and pelvic floor. This study conceptualized MVs and their role in bladder viability. Increased MVs confer an increased risk of failed BNC. When considering BNC, CBE patients with 3 or more prior MVs may benefit from a pedicled muscle flap, in addition to HAD and pedicled adipose tissue, to prevent fistula development by providing wellvascularized coverage to further reinforce the BNC.


Ethylene glycol monomethyl ether. I. Subchronic vapor inhalation study with rats and rabbits.
Male and female Sprague-Dawley rats and New Zealand White rabbits were exposed to 0, 30, 100 or 300 ppm ethylene glycol monomethyl ether (EGME) vapors 6 hours per day, 5 days per week, for a total of 13 weeks. No rats died prior to scheduled sacrifice, but some rabbits in the 100 and 300 ppm exposure groups died or were sacrificed when moribund during the study. Body weights as well as thymus and testicular weights of rats and rabbits in the 300 ppm group were reduced as a result of the exposures. Hematologic changes occurred in rats and rabbits exposed to 300 ppm. Concentrations of total protein, albumin and globulins in serum of rats (but not rabbits) in the 300 ppm group were lower than for controls. Gross lesions in rats and rabbits exposed to 300 ppm EGME included decreased size of thymus in both sexes, decreased abdominal fat, and small flaccid testes in males. In addition there was decreased lymphoid tissue in some rabbits, as well as a slight-to-moderate decrease in size of testes in 4 of 5 rabbits in the 100 ppm group and in 2 of 5 rabbits exposed to 30 ppm. Treatment-related microscopic lesions included degenerative changes in germinal epithelium of testes in all male rats and rabbits in the 300 ppm group, as well as in 3 of 5 rabbits in the 100 ppm group and 1 of 5 male rabbits in the 30 ppm group. The only effects attributed to exposure to 30 ppm EGME in this study were slight microscopic changes in testes of 1 of 5 male rabbits.


Insight into the mechanisms of activity promotion and SO2 resistance over Fe-doped Ce-W oxide catalyst for NOx reduction.
Ceria-based catalysts for the selective catalytic reduction of NOx with NH3 (NH3-SCR) are always subject to deactivation by sulfur poisoning. In this study, Fe-doped Ce-W mixed oxides, which were synthesized by the co-precipitation method, improved the SCR activity and SO2 durability at low temperatures of undoped Ce-W oxides. The improved low-temperature activity was mainly due to the enhancement of redox properties at low temperatures and more active oxygen species, together with the adsorption and activation of more abundant NOx species, facilitating the "fast SCR" reaction. In the presence of SO2, doping with Fe species effectively prevented sulfate deposition on the CeW catalyst, due to the interaction between Fe, Ce, and W species inducing electron transfer among different metal sites and altering the electron distribution. The competitive adsorption behavior between NO and SO2 was changed by Fe doping, in which the adsorption and oxidation of SO2 were restrained. Besides, the elevated NO oxidation accelerated the decomposition of ammonium bisulfate, causing the SCR reaction to not be greatly suppressed. Hence, Fe-doped Ce-W oxides catalysts showed excellent sulfur resistance. This study provides an in-depth understanding of efficient Ce-based catalysts for SO2-tolerance strategies.


Purification and characterization of a thermostable alkaline protease from alkalophilic Bacillus pumilus.
An investigation was carried out on the purification and characterization of an alkaline protease from Bacillus pumilus MK6-5. An alkalophilic Bacillus pumilus MK6-5 was grown in a laboratory fermenter containing 1% reverse osmosis concentrated cheese whey powder, 0.25% corn steep liquor, 1% glucose, 0.5% tryptone, 1% sodium citrate, 0.02% MgSO4.7H2O and 0.65% Na2CO3 at 35 degrees C and pH 9.6, agitation at 250 rev min(-1) and aeration of 1 vvm for 60 h. When the enzyme was purified using ammonium sulphate precipitation, ion exchange and gel filtration chromatographies, a 26.2% recovery of enzyme with 36.6-fold purification was recorded. The purified protease was found to be homogenous by SDS-PAGE with molecular mass estimate of 28 kDa. The enzyme was optimally active at pH 11.5 and temperature of 55-60 degrees C. The Km and kcat values observed with synthetic substrates at 37 degrees C and pH 8.0 were 1.1 mmol l(-1) and 624 s(-1) for Glu-Gly-Ala-Phe-pNA and 3.7 mmol l(-1) and 826 s(-1) for Glu-Ala-Ala-Ala-pNA, respectively. The kinetic data revealed that small aliphatic and aromatic residues were the preferred residues at the P1 position. Inhibition profile exhibited by PMSF suggested the B. pumilus protease to be an alkaline serine protease. Bacillus pumilus MK6-5 produced a calcium-dependent, thermostable alkaline serine protease. The thermostable alkaline protease from Bacillus pumilus MK6-5 will be extremely useful in ultrafiltration membrane cleaning due to its ability to work in broad pH and temperature ranges, and tolerance to detergents, unlike the mesophilic proteases which face these limitations.


Mechanism of mitochondrial dysfunction and cytotoxicity induced by tropolones in isolated rat hepatocytes.
The mechanism of mitochondrial dysfunction and toxicity induced by the tropolones, beta-thujaplicin (4-isopropyl tropolone), tropolone and tropone, has been studied in freshly isolated rat hepatocytes. Incubation of hepatocytes with beta-thujaplicin (1-4 mM) elicited a concentration and time-dependent cell killing. The toxicity was accompanied by losses of cellular ATP, total adenine nucleotides and glutathione, independently of lipid peroxidation and protein thiol oxidation. The beta-thujaplicin-induced cytotoxicity was enhanced by the pretreatment of hepatocyte suspensions with EDTA (4 mM), a hydrophilic chelator, or by incubation in Ca2+ and Mg2+-deficient Krebs-Henseleit buffer. The partition coefficient of beta-thujaplicin, which formed complex with the divalent cations in Krebs-Henseleit buffer, in n-octanol/buffer was increased either in the presence of EDTA or absence of divalent cations. Comparison of toxic effects based on cell viability and adenine nucleotide levels showed that beta-thujaplicin was more toxic than tropolone or tropone in Krebs-Henseleit buffer containing EDTA (4 mM). The addition of beta-thujaplicin to isolated hepatic mitochondria reduced state 3 respiration with NAD+-linked substrate (pyruvate plus malate) and/or with an FAD-linked substrate (succinate plus rotenone), whereas state 3 respiration of ascorbate plus tetramethyl-p-phenylenediamine (cytochrome oxidase-linked respiration) was not significantly affected by beta-thujaplicin. Further, the addition of these tropolones caused a concentration-dependent increase in the rate of state 4 oxygen consumption, indicating an uncoupling effect. These results indicate that beta-thujaplicin- and tropolone-induced cytotoxicity are associated with an acute ATP depletion via mitochondrial dysfunction related to oxidative phosphorylation and that the induction of cytotoxicity is affected by EDTA or divalent cations.


Downregulation of LAT1 expression suppresses cholangiocarcinoma cell invasion and migration.
Currently, there is no effective treatment for cholangiocarcinoma (CCA), which is the most prevalent in the northeastern part of Thailand. A new molecular target for the treatment of CCA is, therefore, urgently needed. Although L-type amino acid transporter 1 (LAT1) is highly expressed in CCA cells, its role in malignant phenotypes of CCA cells remains unclear. This study aimed to investigate the impact of LAT1 on proliferation, migration, and invasion of KKU-M213 cells, the CCA cells derived from Thai patients with intrahepatic cholangiocarcinoma. Results showed that KKU-M213 cells expressed all LAT isoforms (LAT1, LAT2, LAT3 and LAT4). The expressions of LAT1 and its associated protein 4F2hc were highest whereas those of LAT2 and LAT4 were extremely low. Treatment with 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) reduced L-leucine uptake concomitant with an inhibition of cell motility and, to a lesser extent, on cell proliferation. It also induced a time dependent up-regulation of LAT1 and 4F2hc expressions. Similarly, cell migration and invasion, but not proliferation, were reduced in LAT1 knockdown KKU-M213 cells. In addition, silencing of LAT1 inhibited the expressions of 4F2hc mRNA and protein whereas the expression of microRNA-7, the 4F2hc down-regulator, was increased. Furthermore, the phosphorylation levels of ERK1/2 and p70S6K were reduced after LAT1 knockdown. Collectively, these results suggest that suppression of cell invasion and migration in LAT1 knockdown KKU-M213 cells may be partly mediated through the inhibition of the 4F2hc-signaling pathway by the up-regulation of microRNA-7. Based on this finding, LAT1 may be a potential therapeutic target for treating CCA.


Propranolol in DOCA hypertensive rats: development of hypertension inhibited and pressor responsiveness enhanced.
D,L-Propranolol given in single doses by gavage or s.c. injection to awake rats, always slowed the heart without affecting blood pressure. Doses of 0.2 mg/100 g injected twice daily lowered systolic pressure after 3 days in DOCA hypertensive but not in normotensive or spontaneously hypertensive rats. When chronic treatment with propranolol preceded the induction of DOCA hypertension, the pressure elevation attained 14 weeks later was less in treated than in untreated rats. Pressor responses to injected norepinephrine and to posterior hypothalamic stimulation were significantly larger in DOCA hypertensive rats that had been treated chronically with propranolol than in those that had not. These results suggest that propranolol's antihypertensive effects are unimpressive because they are simultaneously opposed by an enhanced cardiovascular responsiveness to pressor stimuli.


Oral exposure to a hexafluoropropylene oxide trimer acid (HFPO-TA) disrupts mitochondrial function and biogenesis in mice.
Hexafluoropropylene oxide trimer acid (HFPO-TA) is reported to have hepatotoxicity, lipotoxicity, and cytotoxicity. In this study, the toxicological effects of HFPO-TA on mitochondrial function and biogenesis were studied. Mice were exposed to drinking water which contained either 2, 20, or 200 μg/L HFPO-TA. Results showed exposure to HFPO-TA induced disadvantageous physiological changes in mice, including increases in liver weight, altered cell morphology, and inflammatory responses. Specifically, exposure to 200 μg/L HFPO-TA increased mitochondria number, relative mitochondrial DNA (mtDNA) content, and mRNA levels of mitochondrial genes encoded by mtDNA. Significant increases in TFAM mRNA and protein levels were also observed. Liver metabolome analysis also showed exposure to 200 μg/L HFPO-TA further enhanced increases in metabolites and altered metabolic pathways that correlated with mitochondrial function, especially the production of ATP. HFPO-TA exposure increased protein expression of mitochondrial complex I-V, and the activities of key enzymes involved in TCA cycle (α-ketoglutarate dehydrogenase, citrate synthase, and succinate dehydrogenase). Furthermore, exposure to 200 μg/L HFPO-TA significantly up-regulating mRNA and protein levels of Opa1, Mfn1, Mfn2, Fis1, and Mff, but did not change Drp1. These findings suggest HFPO-TA could have detrimental effects on health of animals, particularly it was associated with disrupted mitochondrial energy metabolism.


Tight binding of glucocorticoid-receptor complexes to histone-agarose.
"Activated" glucocorticoid-receptor complexes purified about 3,000-fold from rat liver were found to bind to histone-agarose. Because of their tight binding, they could not be eluted from the column by high salt solution (3 M KCl) or low salt plus polyol buffer (50% ethylene glycol), but their binding could be disrupted by pyridoxal 5'-phosphate; more than 70% recovery of the "activated" receptor complexes was achieved with buffer containing 20 mM pyridoxal 5'-phosphate. This interaction of "activated" glucocorticoid-receptor complexes of rat liver with histone-agarose suggests a role of histones in the mechanism of action of steroid hormone.


Mode of action of amiloride in toad urinary bladder. An electrophysiological study of the drug action on sodium permeability of the mucosal border.
The effect of amiloride on the sensitivity to Na of the mucosal border of toad urinary bladder was investigated by recording Na concentration-dependent transepithelial potential difference (Vt) and the intracellular potential. When mucosal Na concentration was normal, amiloride added to the mucosal solution at 10(-4) M markedly reduced the mucosal membrane potential (Vm) and altered the potential profile from a two-step type to a well type. Similar changes were observed when Na was totally eliminated from the mucosal medium. The serosal membrane potential was insensitive to amiloride and elimination of mucosal Na. In the absence of amiloride, the Vt could be described by the Goldman-Hodgkin-Katz equation in the range of mucosal Na concentration from 0 to 16 mM, and amiloride extended this concentration range. By using the Goldman-Hodgkin-Katz equation. Na permeability was calculated from the data of Vt's obtained in the allowed ranges of Na concentration and compared before and after the addition of amiloride. The results show that Na permeability decreases to 1/600 of control when the maximum dose of amiloride (10(-4) M) is applied. The relationship between Na permeability and amiloride concentration is well explained on the basis of assumptions that amiloride binds to the Na site of the mucosal border in one-to-one fashion and in a competitive manner with Na and that Na permeability reduces in proportion to increase in number of the sites bound with amiloride.


An in vitro model of ethanol-dependent liver cell injury.
Primary cultures of adult rat hepatocytes were incubated (6 to 96 hr) with 50 to 150 mmol/L ethanol, 0.5 mmol/L linoleate, 0.5 mmol/L palmitate, 0.5 mmol/L 4-methylpyrazole, 0 to 25 mumol/L vitamin E phosphate or selected combinations of these agents. Agent-dependent changes in liver cell viability (AST release and reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and function (phospholipid peroxidation, hydrolysis, biosynthesis and triacylglycerol biosynthesis) were determined. The influence of ethanol on liver cell function and viability was dose and incubation time dependent. Short periods (24 hr or less) of exposure to 100 mmol/L ethanol increased liver cell triacylglycerol biosynthesis and phospholipid hydrolysis, peroxidation and biosynthesis without altering cell viability. However, longer periods (72 hr or more) of exposure to 100 or 150 mmol/L ethanol resulted in significant reductions (30% to 50%) in cell viability, function and phosphatidylcholine biosynthesis and content. The ethanol-dependent decreases in cell function and viability were potentiated by linoleate and reduced by vitamin E phosphate, palmitate and 4-methylpyrazole. These results suggest that ethanol-induced liver cell injury in vitro is not a result of ethanol per se, but factors such as acetaldehyde or oxyradicals produced as a consequence of ethanol metabolism. Therefore the incubation of cultured hepatocytes with ethanol may be an appropriate model in vitro for determining the mechanisms by which ethanol intake disrupts liver cell function in vivo.


Intrafollicular action of estrogen in regulating pituitary-induced ovarian progesterone synthesis and oocyte maturation in Rana pipiens: temporal relationship and locus of action.
Previous studies demonstrated that estrogen inhibited frog pituitary homogenate (FPH) and progesterone-induced oocyte maturation. In order to determine whether estrogen interfered with intrafollicular progesterone synthesis, experiments were designed to study the effect of exogenous estrogen (estradiol-17 beta) on FPH-induced progesterone production in amphibian (Rana pipiens) ovarian follicles cultured in vitro. Intrafollicular progesterone concentrations were monitored directly using radioimmunoassay and the occurrence of germinal vesicle breakdown (GVBD) was used as a biological indicator of the action of steroids on oocyte maturation. FPH elicited a rapid and dramatic increase in follicular progesterone concentration (1000-3000 pg per follicle) which preceded germinal vesicle breakdown. Addition of estrogen to the culture medium inhibited FPH-induced progesterone production and the accompanying GVBD in a dose-dependent fashion. The presence of estrogen did not enhance the degradation of preloaded progesterone, suggesting estrogen impeded progesterone synthesis rather than enhanced progesterone metabolism. The temporal relationship between estrogen and FPH interaction was assessed by varying the relative time of hormone addition, after which intrafollicular progesterone concentration and GVBD were monitored. Progesterone production and GVBD were drastically inhibited when estrogen was added before or simultaneously with FPH. However, when addition of estrogen was delayed until after FPH simulation, a progressive loss of the inhibitory effect of the steroid on progesterone accumulation and GVBD was observed. Thus, the estrogen-sensitive phase was confined to the early portion of FPH stimulation. Continuous presence of estrogen in the culture system was not required to inhibit FPH-induced events. A short exposure (15 min) of follicles to estrogen was sufficient to inhibit oocyte maturation, whereas progesterone synthesis was not significantly affected. With longer exposure, however, FPH-induced progesterone production was impeded. Washing estrogen-treated follicles did not reverse the inhibitory effect of estrogen, however the follicles remained responsive to exogenous progesterone stimulation and exhibited GVBD. Results suggest that the inhibitory effects of estrogen on FPH action and progesterone production were not reversible under the in vitro culture conditions. To determine whether specific follicular components were involved in estrogen inhibition, progesterone production was assessed following selective removal of different follicle components by microdissection prior to being treated with FPH and estrogen.(ABSTRACT TRUNCATED AT 400 WORDS)


Rutin-encapsulated chitosan nanoparticles targeted to the brain in the treatment of Cerebral Ischemia.
Rutin, a potent antioxidant, has been reported to reduce the risk of ischemic disease. Our study aims to prepare rutin-encapsulated-chitosan nanoparticles (RUT-CS-NPs) via ionic gelation method and determine its results, based on different parameters i.e. surface morphology characterization, in-vitro or ex-vivo release, dynamic light scattering and differential scanning calorimetry (DSC), for treating cerebral ischemia. UPLC-ESI-Q-TOF-MS/MS was used to evaluate the optimized RT-CS-NPs1 for brain-drug uptake as well as to follow-up the pharmacokinetics, bio-distrbution, brain-targeting efficiency and potential after intranasal administration (i.n.). A particle size of <100nm for the formulation, significantly affected by drug:CS ratio, and entrapment efficiency and loading capacity of 84.98%±4.18% and 39.48%±3.16%, respectively were observed for RUT. Pharmacokinetics, bio-distribution, brain-targeting efficiency (1443.48±39.39%) and brain drug-targeting potential (93.00±5.69%) showed enhanced bioavailability for RUT in brain as compared to intravenous administration. In addition; improved neurobehavioral activity, histopathology and reduced infarction volume effects were observed in middle cerebral artery occlusion (MCAO) induced cerebral ischemic rats model after i.n. administration of RUT-CS-NPs. A significant role of mucoadhesive-RT-CS-NPs1 as observed after high targeting potential and efficiency of the formulation prove; RUT-CS-NPs are more effectively accessed and target easily the brain.


Dynamics of cardiorespiratory function in Standardbred horses during different intensities of constant-load exercise.
Six Standardbred horses were used to evaluate the time course of pulmonary gas exchange, ventilation, heart rate (HR) and acid base balance during different intensities of constant-load treadmill exercise. Horses were exercised at approximately 50%, 75% and 100% maximum oxygen uptake (VO2 max) for 5 min and measurements taken every 30 s throughout exercise. At all work rates, the minute ventilation, respiratory frequency and tidal volume reached steady state values by 60 s of exercise. At 100% VO2 max, the oxygen consumption (VO2) increased to mean values of approximately 130 ml/kg.min, which represents a 40-fold increase above resting VO2. At the low and moderate work rates, VO2 showed no significant change from 30 s to 300 s of exercise. At the high work rate, the mean VO2 at 30 s was 80% of the value at 300 s. The HR showed no significant change over time at the moderate work rate but differing responses at the low and high work rates. At the low work rate, the mean HR decreased from 188 beats/min at 30 s to 172 beats/min at 300 s exercise, whereas at the high work rate the mean HR increased from 204 beats/min at 30 s to 221 beats/min at 300 s exercise. No changes in acid base status occurred during exercise at the low work rate. At the moderate work rate, a mild metabolic acidosis occurred which was nonprogressive with time, whereas the high work rate resulted in a progressive metabolic acidosis with a base deficit of 16 mmol/l by 300 s exercise.(ABSTRACT TRUNCATED AT 250 WORDS)


Peroxide solvation by a toroidal lithium inverse crown ether complex assembled by multidentate polyimido sulfonates.
In this communication we present the synthesis of the inverse crown ether complex [Li(2)O(2)·Li(4){CH(2)(N(Me)CH(2)S(NtBu)(2))(2)}(2)] (1) which is able to accommodate peroxide in a torus of lithium ions.


Using 3.0 eV Large Bandgap Conjugated Polymer as Host Donor to Construct Ternary Semi-Transparent Polymer Solar Cells: Increased Average Visible Transmittance and Modified Color Temperature.
Although optical engineering strategy has been utilized to optimize average visible transmittance (AVT) of semi-transparent organic solar cells (ST-OSCs), judicious selection of active layer materials should be more direct and basic. Herein, an efficient ternary active layer is constructed with a wide bandgap (3.0 eV) fluorescent polymer FC-S1 as host donor, a middle bandgap polymer PM6 as guest donor, and a narrow bandgap non-fullerene Y6-BO as acceptor. Using FC-S1 as the host donor can allow more visible photons to penetrate the device. In the absence of optical engineering, the ternary ST-OSC with FC-S1:PM6:Y6-BO = 1:0.3:1.5 active layer of 30 nm thickness displays a much higher AVT of 49.28% than that of 32.34% for a PM6:Y6-BO = 1.3:1.5 based binary ST-OSC. The ternary ST-OSC provides a good power conversion efficiency of 6.01%, only slightly lower than 7.15% for the binary ST-OSC. The ternary ST-OSC also demonstrates a color rendering index (CRI) of 87 and a correlated color temperature (CCT) of 6916 K, all better than CRI of 80 and CCT of 9022 K for the binary ST-OSC. Moreover, the backbone of FC-S1 is mainly composed by fluorene and carbazole, two easily-accessible aromatic rings, which would meet low-cost concern of ST-OSCs.


Magnetic resonance imaging of spinal meningiomas and neurinomas. Improvement of imaging by paramagnetic contrast enhancement.
The detection and delineation of spinal tumors by magnetic resonance imaging (MRI) after intravenous administration of gadolinium (Gd)-diethylenetriaminepenta-acetic acid (DTPA) is demonstrated in eight cases of neurinoma or meningioma. The advantages of Gd-DTPA-enhanced MRI over other MRI techniques used in more than 100 cases of spinal cord diseases are described.


Population forecasting standards: some considerations concerning their necessity and content.
This paper discusses the nature of population forecasting and provides guidelines for standards that are in line with good professional practice yet do not stifle creativity or technical advances.


The prognostic value of expression of HIF1α, EGFR and VEGF-A, in localized prostate cancer for intermediate- and high-risk patients treated with radiation therapy with or without androgen deprivation therapy.
Androgens stimulate the production of hypoxia-inducible factor (HIF1α) and ultimately vascular endothelial growth factor (VEGF-A). Additionally, epithelial growth factor (EGF) mediates HIF1α production. Carbonic anhydrase IX (CAIX) expression is associated with tumor cell hypoxia in a variety of malignancies. This study assesses the prognostic relation between HIF1α, VEGF-A, EGF Receptor and CAIX expression by immunochemistry in diagnostic samples of patients with intermediate- and high-risk localized prostate cancer treated with radiation therapy, with or without androgen deprivation therapy (ADT). Between 1994 and 2004, 103 prostate cancer patients (mean age, 68.7 ± 6.2), with prostate cancer (mean PSA, 13.3 ± 3.7), were treated with radiation therapy (RT, median dose, 74 Gy). Fifty seven (55.3%) patients received ADT (median duration, 6 months; range, 0 - 24). Median follow-up was 97.6 months (range, 5.9 - 206.8). Higher EGFR expression was significantly (p = 0.04) correlated with higher Gleason scores. On univariate analysis, HIF1α nuclear expression was a significant (p = 0.02) prognostic factor for biological progression-free survival (bPFS). A trend towards significance (p = 0.05) was observed with EGFR expression and bPFS. On multivariate analysis, low HIF1α nuclear (p = 0.01) and high EGFR (p = 0.04) expression remained significant adverse prognostic factors. Our study suggests that high nuclear expression of HIF1α and low EGFR expression in diagnostic biopsies of prostate cancer patients treated with RT ± ADT is associated with a good prognosis.


An investigation into bisphenol A leaching from materials used intraorally.
In this study, the authors quantitatively determined the bisphenol A (BPA) leached from intraoral materials during simulated intraoral exposure. The authors subjected samples of intraoral materials to simulated abrasion, immersion in artificial saliva, thermal shock via temperature cycling, and simulated intraoral exposure. The authors collected sample aliquots for up to 2 weeks after artificial saliva immersion, derivatized, and then analyzed the aliquots for BPA by gas chromatography and mass spectroscopy. Quantifiable amounts of leached BPA were observed from only 1 of 13 intraoral materials tested: a silicone baby bottle nipple (20 micrograms). BPA leaching was only observed after 3 days of artificial saliva immersion, with no additional leaching thereafter. Under the test conditions, BPA was observed to leach from a silicone baby bottle nipple. Although the quantities of leached BPA were below the reference dose for daily intake, investigators have shown a possible association between low levels of BPA and many medical disorders. BPA exposure, and thus the use of the leaching material identified in this study, should be reduced or eliminated.


Endoscopic or Surgical Resection for Patients with 2-5cm Gastric Gastrointestinal Stromal Tumors: A Single-Center 12-Year Experience from China.
The surgical or endoscopic resection is the current treatment modality for 2-5 cm gastric gastrointestinal stromal tumors (GISTs). However, evidence is lacking as to which treatment modality is better. Our objective is to provide a new reference for the standardization of the treatment of 2-5 cm gastric GISTs. A retrospective study was conducted on 177 patients who underwent resection for 2-5cm gastric GISTs between January 2007 and July 2019 at Xiangya Hospital of Central South University. The cases were divided into surgical group (n=118) and endoscopic group (n=59). The clinical data, pathological and genetic characteristics, short- and long-term outcomes were compared. Symptoms showed more obvious in the surgical group including abdominal pain and bleeding. In the endoscopic group, tumor size was smaller (p<0.001), and risk classification was lower (p<0.001). Patients in the endoscopic group had shorter anal exhaust time (p<0.001) and lesser hospital cost (p<0.001). However, the incidence rate of complications (25.42 vs 4.20%; p<0.001) and reoperation (22.03 vs 0.00%; p<0.001) in the endoscopic group was relatively higher than these in the surgical group. There was no significant difference in recurrence-free survival or overall survival between two groups. Gastric GISTs of 2-5cm may be suitable to select laparoscopic surgery.


Relation of 97T polymorphism in KCNE5 to risk of atrial fibrillation.
The 97T polymorphism of the KCNE5 gene, coding for an inhibitory beta-subunit, MiRP4, of the repolarizing cardiac potassium ion channel KCNQ1, was significantly more frequent in 96 controls than in 158 patients with atrial fibrillation (AF). KCNQ1 is involved in cardiac action potential, and increased function has been associated with AF. Because the KCNE5 gene is located on the X chromosome, the protection conferred by the 97T polymorphism may help explain the gender-related difference in the risk of AF.


A monolithic silicon based integrated signal generation and detection system for monitoring DNA hybridisation.
The aim of this work was to develop an integrated solution to DNA hybridisation monitoring for diagnostics on a monolithic silicon platform. A fabrication process was developed incorporating a gold initiation electrode patterned directly onto a PIN photodiode detector. Patterned interdigitated type electrodes exhibited the smallest reduction in photodiode sensitivity, therefore these were chosen as the ECL initiator design. A novel DNA hybridisation assay was developed based on the displacement of a partially mismatched complementary strand by a perfectly matched labelled complementary strand. Pre-hybridised thiolated oligonucleotide and unlabelled 25% mismatched oligonucleotide were assembled on the gold initiation electrode. On addition of the labelled perfectly complementary oligonucleotide, the mismatched strands were displaced and a signal was generated. The sensitivity of the photodiode to light emitted at 620 nm, the ruthenium emission wavelength, was determined and subsequently, the diode current response to light generated by flow addition of ruthenium solution was found to be measurable to a concentration of 10 fM. Pre-hybridised duplex DNA, consisting of thiolated oligonucleotide and ruthenium labelled complementary oligonucleotide, was assembled on the gold initiation electrode. The difference between the current measured during flow of buffer and the ECL co-reactant TPA was three orders of magnitude, indicating that DNA assembled on the surface comprised sufficient ruthenium to generate a measurable signal. Finally, the displacement of unlabelled partial mismatch oligonucleotide from the sensor surface was monitored on addition of the ruthenium labelled perfectly complementary oligonucleotide in TPA flow and the measured photodiode current response was up to 50 times greater.


Evaluation of a new radiographic technique: diagnostic accuracy for mandibular third molars.
To compare the accuracy of Scanora with that of traditional panoramic and intra-oral radiography for the assessment of impacted mandibular third molars. Two hundred and fifty-four patients referred for removal of impacted or partly erupted third molars were randomly allocated to one of two groups; 133 were examined by the Scanora system and 121 by a panoramic plus a series of three intra-oral radiographs. The radiographs were read by a trained oral radiologist and her diagnoses validated against the surgeons' findings at operation. There was agreement about the state of tooth eruption in 71.4% of Scanora and 74.4% of conventional examinations and about tooth position in 77.2 and 69.7% respectively (P < 0.05). The number of roots was assessed more accurately by Scanora (82.7% agreement) than by conventional (71% agreement) examination (P < 0.05). There was agreement about the root morphology in 70.4% of Scanora and 62.4% of conventional examinations. In 12% of the patients, the roots were in very close contact with the canal determined by the surgeon. In approximately 50% of these cases, the close contact to the canal was found by radiography with no significant differences between the methods. The Scanora method was more accurate when validated against the surgeons' findings for the position and number of roots of ectopic mandibular third molars while both methods were equally accurate in demonstrating the relation between the roots and the inferior alveolar nerve.


Self-assembly of pH-sensitive random copolymers: poly(styrene-co-4-vinylpyridine).
A series of pH-sensitive random copolymers, poly(styrene-co-4-vinylpyridine) (PSVP), with molecular weight about 10,000 and 4-vinylpyridine molar contents of 19-53%, were conveniently synthesized by free radical polymerization. The copolymers experience the formation, swell, and dissociation of multichain nanoparticles when the pH of the aqueous solutions/dispersions changes from 5.1 to 1.0. The nanoparticles have hydrodynamic diameters around 100 nm, a spherical shape, and a relatively uniform structure in a pH range of about 5-3 and a multicore structure at lower pH. The random distribution of the building units causes some of the hydrophilic units, protonated 4-vinylpyridine groups, to be trapped inside the nanoparticles. So the hydrophobicity of the nanoparticles is tunable by changing the 4-vinylpyridine content in the copolymers. For the copolymers with higher 4-vinylpyridine molar content, the pH range in which the multichain nanoparticles form shifts to higher values, the multichain nanoparticles dissociate, and the copolymers form single-chain hydrophobic domains at low pH.


Glucosinolates from Cardaria draba.
A new glucosinolate salt, L-prolinium 4-(methylsulfinyl)butyl glucosinolate, was isolated from the flowering heads of Cardaria draba and characterized by current spectroscopic methods.


Necrotizing myopathy as a remote effect of gastric cancer accompanied with Hashimoto's thyroiditis.
An autopsy case of a 74-year-old male who had shown clinically hypothyroidism due to chronic atrophic thyroiditis (Hashimoto's thyroiditis), and pathologically necrotizing myopathy as a remote effect of gastric cancer was reported. Morphological features of this necrotizing myopathy was those of carcinomatous myopathy rather than those of hypothyroid or diabetic myopathy. As for the pathogenesis of the necrotizing myopathy (as a Group IV of polymyositis of Walton and Adams), the malignancy might have played an important role as a trigger of the secondary immunological abnormality upon a pre-existing longstranding immune disorder of Hashimoto's thyroiditis. Pseudomembranous colitis, which was thought to be related to antibiotics. (Lincomycin), was also briefly discussed.


Diagnosis and management of the coronary-subclavian steal syndrome.
A patient is presented with recurrent angina due to a coronary-subclavian steal syndrome 3 years after left internal mammary to left anterior descending coronary artery bypass grafting. Myocardial ischaemia could easily be provoked by selective exercise of the left upper limb. Coronary angiography showed reversal of flow in the left internal mammary artery. Suggestions are given for prevention of the coronary-subclavian steal syndrome by identification of patients who are at risk of developing subclavian artery occlusive disease. Performance of coronary and brachiocephalic angiography is indicated in recurrence of angina in patients with internal mammary artery bypass grafts. Doppler spectral analysis may be a valuable technique for detection of a haemodynamically significant stenosis of the left subclavian artery. Carotid-subclavian bypass grafting is the procedure of choice for management of the coronary-subclavian steal syndrome.


Anxiety in multiple sclerosis is related to depressive symptoms and cognitive complaints.
Multiple sclerosis (MS) patients suffer from high levels of anxiety. However, it is unclear which factors are related to anxiety, since study results are inconsistent, and the associated factors have not been examined comprehensively. In this study, we investigated the demographic, disease-related and psychological factors associated with anxiety in MS patients. Cross-sectional data of 119 MS patients were used. Anxiety and depressive symptoms (Hospital Anxiety and Depression Scale), fatigue (Fatigue Severity Scale), cognitive complaints (Cognitive Failures Questionnaire) and cognitive functioning (Wisconsin Card Sorting Test, Controlled Oral Word Association Test, Letter Digit Substitution Test, Concept Shifting Test, Wechsler Memory Test Faces and the Dutch version of the California Verbal Learning Test) were measured. Bivariate and multivariable regression analyses were conducted to test the associations between anxiety and potential contributing factors. In this sample, 42% of the MS patients had clinically significant levels of anxiety, defined by a score ≥8 on the anxiety subscale of the Hospital Anxiety and Depression Scale (HADS). A significant correlation was found between anxiety and depressive symptoms, fatigue, cognitive complaints and psychiatric history. In the multivariable analysis, only depressive symptoms and cognitive complaints remained significantly related to anxiety. Anxiety is common in MS patients and most strongly related to psychological factors. This knowledge can be taken into account when treating patients with MS. Further research is needed using longitudinal designs and incorporating other factors known to influence anxiety, such as coping, negative affectivity and social support.


Magnetic orientation of sphingomyelin-lecithin bilayers.
Phospholipid bilayers consisting of a 60:40 mixture of N-palmitoylsphingomyelin and dimyristoylphosphatidylcholine orient in a strong magnetic field. The orientation is easily observed in 31P- and 2H-nuclear magnetic resonance spectra where the intensity of the perpendicular edges of the powder lineshapes are enhanced. The lineshapes indicate that the long axis of the molecule is perpendicular to the magnetic field.


Intimate partner violence in older South African women: An analysis of the 2016 Demographic and Health Survey.
South Africa (SA) has one of the highest rates of intimate partner violence (IPV) in the world. It is also in the midst of a demographic transition in which the number of people aged >60 years is expected to double by mid-century. Despite the confluence of these two public health issues, there are no published studies on the epidemiology and risk factors for IPV in older SA women. To provide a foundational understanding of IPV among women aged ≥50 years in SA. This study used the first-ever nationally representative sample of women aged >49 (N=2 265) that includes data on physical, sexual, and emotional IPV. Both lifetime experience of IPV and IPV within the past 12 months were reported, as was the presence of controlling behaviours by the partner. Four multilevel logistic models and one multilevel linear regression model were fit to examine the demographic, developmental and structural correlates of IPV in women aged 50 - 95. The lifetime prevalence rates for all types of IPV were slightly higher among older women than among women aged 15 - 49. Nine percent of respondents reported IPV in the past 12 months, and 35% reported at least one persistent controlling behaviour. Divorced/separated women and those who had witnessed IPV as a child had greater odds of reporting IPV. In contrast to the literature on younger women, education, race and wealth were not strong predictors of IPV in this sample of older women. This study is the first of its kind in the SA context, and shows that IPV is a persistent threat for women across the lifespan. It suggests that IPV may manifest differently in older women compared with women of reproductive age, necessitating future qualitative and quantitative studies that examine the correlates, causes and points of intervention unique to this growing population.


Inhibitory effects of suramin on androgen-dependent and -independent growth of neonatal mouse seminal vesicles in vitro.
The effects of suramin on the growth of seminal vesicles (SVs) of neonatal mice were investigated in vitro. SVs from 0-day-old male mice were cultured in serum-free chemically defined medium supplemented with 5 alpha-dihydrotestosterone (DHT, 10(-8) M) and insulin (10 micrograms/ml), alone and in combination. Prior to culture, SVs from 0-day-old mice had no epithelial branches. SVs cultured in medium with DHT formed numerous epithelial branches, while epithelial branching did not occur in SVs cultured without DHT. The addition of suramin (0.2 mM) to medium containing DHT inhibited the formation of epithelial branches almost completely. Removal of suramin from the medium on days 2, 4, and 6 of culture initiated the formation of epithelial branches. Suramin (0.2 mM) reversibly decreased 3H-thymidine-labeling indices (3H-LI) of both epithelium and mesenchyme of SVs cultured in medium with DHT plus insulin or DHT alone during 8 days of culture. Suramin also decreased 3H-LI of both epithelium and mesenchyme of SVs cultured in medium with insulin alone. The present study indicates that suramin reversibly inhibits not only androgen-dependent but also androgen-independent growth and ductal branching morphogenesis of neonatal mouse SVs.


Comprehensive two-dimensional gas chromatography in metabolomics.
One of the major objectives in metabolomics is the identification of subtle changes in metabolite profiles as affected by genetic or environmental factors. Comprehensive two-dimensional gas chromatography (GC × GC) hyphenated to a fast-acquisition mass spectrometer is a well-established analytical technique to study the composition of complex samples due to its enhanced separation capacity, sensitivity, peak resolution, and reproducibility. This review reports applications of GC × GC to metabolomics studies of sample of different types (biofluid, cells, tissue, bacteria, yeast, plants), and discusses its advantages and limitations.


Colorectal carcinoma prognosis can be predicted by alterations in gene p53 exons 5 and 8.
Gene p53 alteration is a genetic event described in the progression from adenoma to colorectal carcinoma. Most of the p53 mutations occur in exons 5 to 8 in highly preserved regions and in the three main structural domains of the p53 protein. It is possible that mutations affecting different structural regions may present different effects on the p53 protein function and, due to this, they may have different prognostic meaning. The study population consisted of 353 patients diagnosed with sporadic colorectal cancer. Mutations in 5-8 exons of p53 gene were detected by means of single strand conformation polymorphism (SSCP). All samples that showed different migration bands in SSCP were confirmed by sequencing. A total of 69 patients (19.7%) showed alterations of the gene p53. It was observed that mutation in codon 175 in exon 5 was related to tumors located in the colon (p = 0.01) and the mutation in the codon 288 in exon 8 was related to rectal tumors (p = 0.02). In the study of overall survival, mutation in codon 175 of exon 5 conferred a better prognosis and alterations of exon 8 were related to a worse prognosis in different population subgroups: in men, in patients younger than 71 years old, in the tumors located in the proximal colon, the ones moderately differentiated, and those that are mucinous. According to this study, mutations in different exons of p53 are related to different phenotypes in colorectal cancer. These phenotypes could mean differences in the clinical evolution of the patients.


Successful modulation of portal inflow by somatostatin in a porcine model of small-for-size syndrome.
Somatostatin may prevent the small-for-size syndrome in subjects undergoing extended hepatectomy by decreasing portal pressure. Twenty pigs underwent 70% hepatectomy (H70 group, n = 7), 90% hepatectomy (H90 group, n = 7), or sham laparotomy (control group, n = 6). Splanchnic hemodynamics was measured before and after an intraoperative infusion of somatostatin. The portal vein flow normalized to liver weight increased in both H70 and H90 groups (from 125 ± 42 to 342 ± 82 mL/min/100g, P = .031 and from 140 ± 46 to 530 ± 241, P = .016, respectively). The hepatic venous pressure gradient (HVPG) increased in the H90 group only (from 5.5 ± 5.8 to 13 ± 4.9 mm Hg, P = .004). Somatostatin decreased portal vein flow normalized to liver weight in both H70 and H90 groups (from 408 ± 224 to 360 ± 227 mL/min/100g, P = .031 and from 560 ± 190 to 466 ± 189 mL/min/100g, P = .016), and restored a normal HVPG in the H90 group (from 14.3 ± 4.8 to 7.7 ± 6.1 mm Hg, P = .047). Somatostatin restores a normal HVPG in the setting of small-for-size syndrome and can be considered as an effective pharmaceutical modality of portal inflow modulation after extended hepatectomy.


Combined orientation and colour information in human V1 for both L-M and S-cone chromatic axes.
Although it is widely held that colour and form are processed separately in early visual cortex, there is growing evidence that primary visual cortex (V1) may show some joint selectivity for orientation and colour. Colour is supplied to V1 via two very different pathways: the parvocellular pathway (which also supports detailed form processing) carries L-M ("red-green") chromatic information, while a koniocellular pathway carries S-cone ("lilac-yellow") information. Therefore on entering V1, S-cone information is segregated from the pathways carrying form information, while L-M information is not. Whether signals from neuronal populations in human V1 reflect combined orientation and S-cone information has not been systematically addressed. We used fMRI in combination with a multivariate data analysis technique to investigate whether BOLD signals recorded from V1 contain information that could directly discriminate between orientations based on different types of chromatic information. We found selectivity in V1 for L-M and luminance-defined orientation signals, and most interestingly, also for S-cone defined orientation. We also found similarly successful orientation discrimination for both colour dimensions in V2 and V3. These results imply that a proportion of cells throughout human visual cortex show joint sensitivity to both colour and orientation. We discuss also the potential role of feedback to V1 from higher visual areas.


Type 1 protein tyrosine kinases in benign and malignant breast lesions.
To determine their significance, we examined the expression pattern of the four epidermal growth factor receptor (EGFR) family members as well as the phosphotyrosine kinase activity in breast tumour tissues. Fifty-three malignant breast tumours, four breast cancer cell lines, and 10 benign breast tumours were investigated. Fifty-three per cent (28/53) of the malignant tumours expressed EGFR protein, and the majority of these positive tumours were strongly positive. Eighty per cent (8/10) of the benign tumours also expressed EGFR protein, but all in a lower or moderate level. An association between EGFR expression and increasing malignancy grade was found in the group of infiltrating ductal carcinomas. Of the malignant tumours, 35.8% (19/53) expressed c-erbB-2 protein and 17% (9/53) c-erbB-3 protein, while no expression of c-erbB-2 and c-erbB-3 proteins was found in the benign tumours. Contrary to previous reports, we observed c-erbB-4 receptor protein to be less expressed in the malignant breast tumours. The 'normal' breast epithelial cells adjacent to the malignant tumours and the benign tumours demonstrated intensified membrane staining for c-erbB-4, while a number of the malignant tumours demonstrated a weak cytoplasmic staining or were negative. However, several malignant tumours with strong membrane staining for the c-erbB-4 protein were also found. No simple association between the expression of the four receptors and phosphotyrosine kinase activity was found. Our study has revealed a complex expression pattern of the EGFR family members in breast tumour cells. While the data about EGFR, c-erbB-2, c-erbB-3 and phosphotyrosine are largely in line with what has been reported, we found the c-erbB-4 protein expression to be decreased in the malignant tumours.


Comparative tribology II-Measurable biphasic tissue properties have predictable impacts on cartilage rehydration and lubricity.
Healthy articular cartilage supports load bearing and frictional properties unmatched among biological tissues and man-made bearing materials. Balancing fluid exudation and recovery under loaded and articulated conditions is essential to the tissue's biological and mechanical longevity. Our prior tribological investigations, which leveraged the convergent stationary contact area (cSCA) configuration, revealed that sliding alone can modulate cartilage interstitial fluid pressurization and the recovery and maintenance of lubrication under load through a mechanism termed 'tribological rehydration.' Our recent comparative assessment of tribological rehydration revealed remarkably consistent sliding speed-dependent fluid recovery and lubrication behaviors across femoral condyle cartilage from five mammalian species (equine/horse, bovine/cow, porcine/pig, ovine/sheep, and caprine/goat). In the present study, we identified and characterized key predictive relationships among tissue properties, sliding-induced tribological rehydration, and the modulation/recovery of lubrication within healthy articular cartilage. Using correlational analysis, we linked observed speed-dependent tribological rehydration behaviors to cartilage's geometry and biphasic properties (tensile and compressive moduli, and permeability). Together, these findings demonstrate that easily measurable biphasic tissue characteristics (e.g., bulk tissue material properties, compressive strain magnitude, and strain rates) can be used to predict cartilage's rehydration and lubricating abilities, and ultimately its function in vivo. STATEMENT OF SIGNIFICANCE: In healthy cartilage, articulation recovers fluid lost to static loading thereby sustaining tissue lubricity. Osteoarthritis causes changes to cartilage composition, stiffness, and permeability associated with faster fluid exudation and presumably poorer frictional outcomes. Yet, the relationship between mechanical properties and fluid recovery during articulation/sliding remains unclear. Through innovative, high-speed benchtop sliding and indentation experiments, we found that cartilage's tissue properties regulate its exudation/hydration under slow sliding speeds but have minimal effect at high sliding speeds. In fact, cartilage rehydration appears insensitive to permeability and stiffness under high fluid load support conditions. This new understanding of the balance of cartilage exudation and rehydration during activity, based upon comparative tribology studies, may improve prevention and rehabilitation strategies for joint injuries and osteoarthritis.


New stereological method for obtaining unbiased and efficient estimates of total nerve cell number in human brain areas. Exemplified by the mediodorsal thalamic nucleus in schizophrenics.
Using a new stereological technique, the total number of nerve and glia cells can be estimated in selected brain regions. The method is completely independent of precise knowledge of nerve cell size, section thickness and of dimensional changes in brain tissue induced by histological procedures. It therefore provides an unbiased estimate of total nerve cell number. As an example, the total neuron number from the mediodorsal nucleus of thalamus in brains from schizophrenic patients is compared to control cases. The total neuron number was reduced by 40% in the brains from chronic schizophrenic patients.


[Cryotherapy of precancerous diseases of the cervix uteri].
In the COR of the USSR Academy of Medical Sciences cryotherapy was employed in 54 patients with pretumor lesions of the uterine cervix. The cryotherapy was performed by a "Spembly" machine (England) and a national apparatus. As a cryoagent nitrogen monoxide was used, which provided the cooling of a cryosonde up to -89 degrees C. This method offers such advantages as the absence of pain, bleeding and complications. An analysis of the immediate results of the treatment allows cryoexposure to be considered an effective method and to employ it under out-patient conditions.


Population-land urbanization and comprehensive development evaluation of the Beijing-Tianjin-Hebei urban agglomeration.
As the main form of the new urbanization strategy, urban agglomeration promotes inter-regional economic development, population flow, and industrial cooperation. It is not only an important platform for the country to participate in international competition, but also an important carrier to explore the multiple influencing factors of urbanization. Based on the Beijing-Tianjin-Hebei urban agglomeration, the temporal and spatial characteristics of its evolution from 1990 to 2020 are analyzed by using the models of urban evolution and industrial transfer. The results show that at the level of urban land use evolution intensity, Beijing > Tianjin > Hebei, and the evolution of urban land use showed an obvious pattern of concentration of resources in central cities (districts) and weak development in sub-central cities (counties). The overall level of urban sprawl showed a downward trend, and only 0.50% of districts and counties were in the stage of high sprawl. Before 2010, the urban sprawl of Beijing, Tangshan, and southern Hebei province remained at a high level, and after 2010, the urban sprawl of central Hebei province remained at a high level. In terms of comprehensive development, the index of cities decreased, including Beijing, Tianjin, and Tangshan, while the index of cities increased including Shijiazhuang, Handan, Xingtai, and Baoding. There is a trend of agglomeration and diffusion of regional industries in geographical space. Middle- and high-end manufacturing industry and service industry gather in the first city, and middle- and low-end processing industry, labor-intensive industry, and agriculture move to surrounding cities. The research results can provide policy suggestions for the coordinated development of regional integration in developing countries.


1,1,2,2,2,3,3,3-Octa-carbonyl-1,1,2,3-tetra-kis-(1,3,5-tri-aza-7-phosphatri-cyclo-[126.96.36.199,7]decane-κP)-triangulo-triosmium(0).
The title compound, [Os3(C6H12N3P)4(CO)8], crystallizes in the ortho-rhom-bic space group Pbca with Z = 8. The mol-ecule consists of a triangular triosmium(0) core surrounded by eight carbonyl ligands and four 1,3,5-tri-aza-7-phosphatri-cyclo-[126.96.36.199,7]decane (or PTA) ligands. One Os atom is coordinated by two PTA ligands and two CO ligands, while the other two Os atoms are each bonded to a single PTA ligand and three CO ligands. There is a small disorder associated with the Os3 unit so that a minor orientation has an occupancy of 2.17 (4)%. The title compound represents the first structurally characterized triangular Os3 carbonyl cluster with four monodentate tertiary phosphane ligands.


Advances in automated real-time flow cytometry for monitoring of bioreactor processes.
Flow cytometry and its technological possibilities have greatly advanced in the past decade as analysis tool for single cell properties and population distributions of different cell types in bioreactors. Along the way, some solutions for automated real-time flow cytometry (ART-FCM) were developed for monitoring of bioreactor processes without operator interference over extended periods with variable sampling frequency. However, there is still great potential for ART-FCM to evolve and possibly become a standard application in bioprocess monitoring and process control. This review first addresses different components of an ART-FCM, including the sampling device, the sample-processing unit, the unit for sample delivery to the flow cytometer and the settings for measurement of pre-processed samples. Also, available algorithms are presented for automated data analysis of multi-parameter fluorescence datasets derived from ART-FCM experiments. Furthermore, challenges are discussed for integration of fluorescence-activated cell sorting into an ART-FCM setup for isolation and separation of interesting subpopulations that can be further characterized by for instance omics-methods. As the application of ART-FCM is especially of interest for bioreactor process monitoring, including investigation of population heterogeneity and automated process control, a summary of already existing setups for these purposes is given. Additionally, the general future potential of ART-FCM is addressed.


Assessing trophic position from nitrogen isotope ratios: effective calibration against spatially varying baselines.
Nitrogen isotope signatures (δ(15)N) provide powerful measures of the trophic positions of individuals, populations and communities. Obtaining reliable consumer δ(15)N values depends upon controlling for spatial variation in plant δ(15)N values, which form the trophic 'baseline'. However, recent studies make differing assumptions about the scale over which plant δ(15)N values vary, and approaches to baseline control differ markedly. We examined spatial variation in the δ(15)N values of plants and ants sampled from eight 150-m transects in both unlogged and logged rainforests. We then investigated whether ant δ(15)N values were related to variation in plant δ(15)N values following baseline correction of ant values at two spatial scales: (1) using 'local' means of plants collected from the same transect and (2) using 'global' means of plants collected from all transects within each forest type. Plant δ(15)N baselines varied by the equivalent of one trophic level within each forest type. Correcting ant δ(15)N values using global plant means resulted in consumer values that were strongly positively related to the transect baseline, whereas local corrections yielded reliable estimates of consumer trophic positions that were largely independent of transect baselines. These results were consistent at the community level and when three trophically distinct ant subfamilies and eight abundant ant species were considered separately. Our results suggest that assuming baselines do not vary can produce misleading estimates of consumer trophic positions. We therefore emphasise the importance of clearly defining and applying baseline corrections at a scale that accounts for spatial variation in plant δ(15)N values.


The cell coat of the olfactory epithelium proper and vomeronasal neuroepithelium of the rat as revealed by means of the Ruthenium-red reaction.
The apical cell coat of the olfactory epithelium proper and the vomeronasal neuroepithelium of the rat was investigated electron-microscopically by means of the Ruthenium-red reaction. In the olfactory epithelium proper, the cilia of receptor cells and microvilli of supporting cells possess a cell coat measuring approximately 10 nm in thickness. In the vomeronasal neuroepithelium, the apical cell coat is thicker than in the olfactory epithelium proper. On microvilli of vomeronasal receptor cells the cell coat varies in thickness from 15 to 20 nm, and on microvilli of supporting cells it measures approximately 75 nm. The functional implications of these findings are discussed.


Investigating the impact of flowable composite liner on the fracture strength and microleakage of large composite resin restorations of primary anterior teeth.
To investigate the effect of pre-cured and co-cured flowable composite liner on fracture strength and microleakage of primary anterior teeth with extended composite resin restorations. In the current in vitro experimental study, the crowns of 54 extracted primary canine teeth were cut 1 mm above the CEJ, and a pulpectomy procedure was performed. The samples were randomly divided into three groups to restore the coronal part up to 4 mm above the CEJ. In group 1, the samples were built up with Filtek Z250 packable composite resin. In group 2 (pre-cure), first, 1 mm of Filtek Z350 XT flowable liner was applied to the sample, and after curing, the restoration process continued using packable composite resin. In group 3 (co-cure), the flowable composite liner was cured while the first layer of packable composite resin was applied; then, the same restorative procedure similar to the other groups was followed. The samples' cross-sectional area in the fracture strength test was calculated by AutoCAD software. Subsequently, the samples were subjected to a force in a universal testing machine. The samples related to the microleakage experiment were cut vertically, and then, the dye penetration percentage (10% methylene blue) was measured under a stereomicroscope. ANOVA was used to analyze the data. Mean fracture strength in group 2 was significantly higher than in group 1 (P = 0.016). The microleakage mean in group 3 was significantly lower than in groups 1 (P = 0.000) and 2 (P = 0.026). The flowable composite liner and its relevant separate curing increased the fracture strength of composite resin restorations. However, less microleakage was reported in the group where the liner was applied as a co-cure.


Ultrastructural and cytochemical analysis of Na+, K+, ATPase and H+, K+, ATPase in parietal cells of gastric mucosa in the rabbit.
Rabbit gastric secretion has the physiological peculiarity of being continuous and uninfluenced by food intake. In this respect, ultrastructural analysis of rabbit parietal cells has revealed morphofunctional features situated between states of rest and very active acid secretion. Our cytochemical study shows that Mg2+ ATPase and ADPase activities vary from cell to cell and can even be totally absent. These activities concern either microcanaliculi or laterobasal folds or both, but never tubulovesicles. Application of the technique of Mayahara to K+ pNPP, associated or not with inhibitors (ouabain, vanadate, N-ethyl-maleimide, sodium fluoride), enabled us to confirm the coexistence of H+, K+, ATPase and Na+, K+, ATPase activities in the rabbit and to determine that these activities concern basolateral folds, microcanaliculi, hyaloplasm and tubulovesicles. The global activity of K+, pNPPase varied considerably in intensity. The results of using inhibitors suggest that proton transport ceases completely in certain cells. The signs of functional alternation found in this study are in agreement with physiological data relative to this animal.


Inotropic effect of noradrenaline and acetylcholine in the rabbit auricle studied by a cut-end method.
Trans-gap application of noradrenaline or acetylcholine evoked pronounced inotropic but no chronotropic effects in spontaneously active rabbit auricle preparations. These results suggest the existence of intracellular receptors, both adrenergic and cholinergic, which were involved in the control of auricular contraction.


Sporadic childhood hepatoblastomas show activation of beta-catenin, mismatch repair defects and p53 mutations.
Hepatoblastoma, a rare embryonic tumor that may arise sporadically or in the context of hereditary syndromes (familial adenomatous polyposis and Beckwith-Wiedemann's) is the most frequent liver cancer of childhood. Deregulation of the APC/beta-catenin pathway occurs in a consistent fraction of hepatoblastomas, with mutations in the APC and beta-catenin genes implicated in familial adenomatous polyposis-associated and sporadic hepatoblastomas, respectively. Alterations in other cancer-related molecular pathways have not been reported. We investigated a series of 21 sporadic paraffin-embedded hepatoblastoma cases for mutations in the p53 (exons 5-8) and beta-catenin (exon 3) genes, loss of heterozygosity at APC, microsatellite instability and immunohistochemical expression of beta-catenin and of the two main mismatch repair proteins, MLH1 and MSH2. No loss of heterozygosity at APC was detected. We found mutations in beta-catenin and p53 in 4/21 (19%) and 5/21 (24%) cases respectively, beta-catenin protein accumulation in 14/21 cases (67%), microsatellite instability in 17/21 cases (81%), of which eight resulted positive for high-level of microsatellite instability (in four cases associated with loss of MLH1/MSH2 immunostaining). No correlations between involved molecular pathway(s) and hepatoblastoma histotype(s) emerged. This study confirms that beta-catenin deregulation is involved in sporadic hepatoblastoma and also suggests that mismatch repair defects and p53 mutations contribute to this rare liver cancer. Sporadic hepatoblastoma appears to be molecularly and phenotypically heterogeneous and may reflect different pathways of liver carcinogenesis.


A Two-Photon Ratiometric Sensing Platform Based on Solid-State Luminescent Benzocoumarin: Application to Prolonged Bioimaging of Hydrogen Peroxide.
Fluorescent probes provide essential tools for studying biological systems. For the prolonged imaging of cellular analytes, the fast clearance of small-molecular probes and products is a matter of concern in the quantitative analysis. Activatable probes that produce insoluble products inside cells can be used for prolonged imaging, but those with ratiometric imaging capability are rare. We disclose a novel sensing platform that is capable of prolonged imaging, in addition to ratiometric signaling for reliable quantitative analysis. Specifically, 3-(pyridin-4-yl)-8-(pyrrolidin-1-yl)-2H-benzo[g]chromen-2-one and its pyridinium salt as a product/probe couple constitute the ratiometric sensing platform. As the former dye produces highly emissive insoluble nanoaggregates inside cells, a fluorescent probe in the latter form enables prolonged imaging of the target analyte in cells as well as in tissue by two-photon microscopy.