Epigenetic modifications of triterpenoid ursolic acid in activating Nrf2 and blocking cellular transformation of mouse epidermal cells.
Ursolic acid (UA), a well-known natural triterpenoid found in abundance in blueberries, cranberries and apple peels, has been reported to possess many beneficial health effects. These effects include anticancer activity in various cancers, such as skin cancer. Skin cancer is the most common cancer in the world. Nuclear factor E2-related factor 2 (Nrf2) is a master regulator of antioxidative stress response with anticarcinogenic activity against UV- and chemical-induced tumor formation in the skin. Recent studies show that epigenetic modifications of Nrf2 play an important role in cancer prevention. However, the epigenetic impact of UA on Nrf2 signaling remains poorly understood in skin cancer. In this study, we investigated the epigenetic effects of UA on mouse epidermal JB6 P+ cells. UA inhibited cellular transformation by 12-O-tetradecanoylphorbol-13-acetate at a concentration at which the cytotoxicity was no more than 25%. Under this condition, UA induced the expression of the Nrf2-mediated detoxifying/antioxidant enzymes heme oxygenase-1, NAD(P)H:quinone oxidoreductase 1 and UDP-glucuronosyltransferase 1A1. DNA methylation analysis revealed that UA demethylated the first 15 CpG sites of the Nrf2 promoter region, which correlated with the reexpression of Nrf2. Furthermore, UA reduced the expression of epigenetic modifying enzymes, including the DNA methyltransferases DNMT1 and DNMT3a and the histone deacetylases (HDACs) HDAC1, HDAC2, HDAC3 and HDAC8 (Class I) and HDAC6 and HDAC7 (Class II), and HDAC activity. Taken together, these results suggest that the epigenetic effects of the triterpenoid UA could potentially contribute to its beneficial effects, including the prevention of skin cancer.


Elucidation of the molecular responses to waterlogging in Jatropha roots by transcriptome profiling.
Jatropha (Jatropha curcas) is a promising oil-seed crop for biodiesel production. However, the species is highly sensitive to waterlogging, which can result in stunted growth and yield loss. To date, the molecular mechanisms underlying the responses to waterlogging in Jatropha remain elusive. Here, the transcriptome adjustment of Jatropha roots to waterlogging was examined by high-throughput RNA-sequencing (RNA-seq). The results indicated that 24 h of waterlogging caused significant changes in mRNA abundance of 1968 genes. Comprehensive gene ontology and functional enrichment analysis of root transcriptome revealed that waterlogging promoted responses to hypoxia and anaerobic respiration. On the other hand, the stress inhibited carbohydrate synthesis, cell wall biogenesis, and growth. The results also highlighted the roles of ethylene, nitrate, and nitric oxide in waterlogging acclimation. In addition, transcriptome profiling identified 85 waterlogging-induced transcription factors including members of AP2/ERF, MYB, and WRKY families implying that reprogramming of gene expression is a vital mechanism for waterlogging acclimation. Comparative analysis of differentially regulated transcripts in response to waterlogging among Arabidopsis, gray poplar, Jatropha, and rice further revealed not only conserved but species-specific regulation. Our findings unraveled the molecular responses to waterlogging in Jatropha and provided new perspectives for developing a waterlogging tolerant cultivar in the future.


[Reversible suppression of cellular aggregation by cytochalasin B and kolkhamin].
Aggregation of normal mouse fibroblast-like cells plated on the surface of millipore filter was studied quantitatively. It was shown that addition of 10 mug/ml of cytochalasin B (a drug which blocked active cell locomotion) or 0.1 mug/ml of colcemid (a drug which destroyed polarization processes in the cells and therefore interfered with the oriented cell movement) completely inhibited such aggregation. This inhibition was reversible: after the drugs were washed off the cells did aggregate. It was concluded that cell aggregation in this experimental system required active cell movement and cell polarization.


Perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), and perfluorononanoic acid (PFNA) increase triglyceride levels and decrease cholesterogenic gene expression in human HepaRG liver cells.
Per- and polyfluoroalkyl substances (PFASs) are omnipresent in the environment, food chain, and humans. Epidemiological studies have shown a positive association between serum levels of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS), and increased serum cholesterol and, in some cases, also triglyceride levels. However, causality has been questioned, as animal studies, as well as a human trial, showed a decrease in serum cholesterol and no effects or a decrease in plasma triglycerides. To obtain more insight into the effects of PFASs on these processes, the present study investigated the effects of PFOA, PFOS, and perfluorononanoic acid (PFNA) on intracellular triglyceride and cholesterol levels in human HepaRG liver cells. DNA microarray analyses were performed to provide insight into underlying mechanisms. All PFASs induced an increase in cellular triglyceride levels, but had no effect on cholesterol levels. Gene set enrichment analysis (GSEA) of the microarray data indicated that gene sets related to cholesterol biosynthesis were repressed by PFOA, PFOS, and PFNA. Other gene sets commonly affected by all PFAS were related to PERK/ATF4 signaling (induced), tRNA amino-acylation (induced), amino acid transport (induced), and glycolysis/gluconeogenesis (repressed). Moreover, numerous target genes of peroxisome proliferator-activated receptor α (PPARα) were found to be upregulated. Altogether, the present study shows that PFOA, PFOS, and PFNA increase triglyceride levels and inhibit cholesterogenic gene expression in HepaRG cells. In addition, the present study indicates that PFASs induce endoplasmic reticulum stress, which may be an important mechanism underlying some of the toxic effects of these chemicals.


Sustainable and Ecofriendly Approach of Managing Soil Born Bacterium Ralstonia solanacearum (Smith) Using Dried Powder of Conyza canadensis.
Bacterial wilt disease caused by Ralstonia solanacearum is a devastating plant disease that inflicts heavy losses to the large number of economic host plants it infects. The potential of dried powder of the Conyza canadensis to control bacterial wilt (BW) of tomato was explored in vitro and in planta. Three application times (16 days before transplanting (DBT), 8 DBT and 0 DBT), three plastic-mulch durations (10 days plastic mulching (DPM), 5DPM and 0DPM) and four doses viz. 0 g, 8 g, 16 g and 24 g of the plant powder were evaluated. SEM analysis was also conducted to observe the change in bacterial cell morphology. Ethanol extract of dried C. canadensis in different concentrations inhibited the in vitro growth of R. solanacearum by as much as 98% of that produced by ampicillin. As evident from the scanning electron micrograph, the highest concentration produced severe morphologic changes, such as rupture of the bacterial cell walls and cell contents leaked out. Results from application time and dose experiment demonstrated that the highest powder dose viz. 24 g kg-1 mixed with infested soil 16 DBT gave maximum root length (34.0 ± 2.5 cm), plant height (74.3 ± 4.7 cm), fresh biomass (58.3 ± 4.3 g), reduction in bacterial population (1.52 log10) and resulted in lowest AUDPC value (1156.6). In case of mulching duration and dose experiment the maximum root length (39.6 ± 3.2 cm), plant height (78.3 ± 5.8 cm), fresh biomass (65.6 ± 4.9 g) reduction in bacterial population (1.59 log10) and lowest AUDPC value (1251.6) was achieved through the application of highest powder dose viz. 24 g kg-1 and longest plastic mulching duration of 10 DPM. The better results of highest dose and longer application time can be explained on the basis of higher amounts of anti-microbial plant bio-active compounds in highest dose and the longer exposure time of the pathogen to these chemicals. The better results of longer mulching duration are due to faster and more complete decomposition (because of 10-days-long plastic-mulch-provided increased solar heat) of the dried powder which produced more amounts of volatile and non-volatile bactericidal compounds. Our results clearly suggest that the use of 24 g kg-1 dried plant powder of C. canadensis plastic-mulched for two weeks could be used as a reliable component of the integrated disease management program against BW.


ZC3H12A/MCPIP1/Regnase-1-related endonucleases: An evolutionary perspective on molecular mechanisms and biological functions.
The mammalian Zc3h12a/MCPIP1/Regnase-1, an extensively studied regulator of inflammatory response, is the founding member of a ribonuclease family, which includes proteins related by the presence of the so-called Zc3h12a-like NYN domain. Recently, several related proteins have been described in Caenorhabditis elegans, allowing comparative evaluation of molecular functions and biological roles of these ribonucleases. We discuss the structural features of these proteins, which endow some members with ribonuclease (RNase) activity while others with auxiliary or RNA-independent functions. We also consider their RNA specificity and highlight a common role for these proteins in cellular defense, which is remarkable considering the evolutionary distance and fundamental differences in cellular defense mechanisms between mammals and nematodes.


Differential induction of interleukin-10 in monocytes by HIV-1 clade B and clade C Tat proteins.
The clade B human immunodeficiency virus, type 1 (HIV-1) Tat (trans-acting regulatory protein) induces interleukin-10 (IL-10) production in monocytes. IL-10, an anti-inflammatory cytokine, down-regulates proinflammatory cytokines and suppresses the immune response, leading to a rapid progression from HIV-1 infection to AIDS. Nine clades of HIV-1 are responsible for the majority of infections worldwide. Recent studies demonstrate that different HIV-1 clades have biological differences in relation to transmission, replication, and disease progression. In this study, we show that the cysteine to serine mutation at position 31, found in >90% of HIV-1 clade C Tat proteins, results in a marked decrease in IL-10 production in monocytes compared with clade B Tat. Additionally, the C31S mutation found in C Tat is responsible for the inability of these Tat proteins to produce high IL-10 levels in monocytes due to its inability to induce intracellular calcium flux through L-type calcium channels. Moreover, we show that p38alpha/p38beta and phosphoinositide 3-kinase are crucial to Tat-induced IL-10 production. These findings provide further evidence that HIV-1 clades differ in their biological properties that may impact HIV-1 pathogenesis and disease progression.


The DNA polymerase beta replication error spectrum in the adenomatous polyposis coli gene contains human colon tumor mutational hotspots.
We have found a significant concordance between the in vitro replication errors of human DNA polymerase beta and in vivo point mutations of the adenomatous polyposis coli (APC) gene that leads to colon cancer. We determined the error spectrum of DNA polymerase beta in the human APC gene under PCR conditions and compared it with the set of mutations reported in human colon tumors. Polymerase beta created seven hotspot mutations within 141 target bp analyzed in APC exon 15. Three of these polymerase beta hotspots, 2 frameshifts and a bp substitution mutation, were concordant with 3 of 13 APC hotspots detected in human colon cancers in the same DNA sequences. These 3 concordant hotspots accounted for some 54% of reported in vivo APC hotspot mutations. Using the assumption of a hypergeometric distribution of hotspot mutations among bp of the scanned sequences, the probability of this concordance occurring by chance is <4 x 10(-4). These data support the hypothesis that DNA polymerase beta errors are an important fraction of cancer-causing APC mutations.


Endoluminal fundoplication--the Hill procedure.
Endoluminal operations for reflux are currently limited by the inability to visualise and manipulate structures outside the wall of the gut. This may be possible using endoscopic ultrasound (EUS). The aim of this study was to define EUS-anatomy of structures outside the gut which influence reflux; to place stitches in the median arcuate ligament (MAL); to perform posterior gastropexy (Hill procedure) and test the feasibility of crural repair under EUS control in pigs. In survival experiments in 14 pigs, using linear array echo-endoscopes the MAL and part of the right crus were identified and punctured with a needle, which served as a carrier for a tag and thread. These were anchored into the muscle. An endoscopic sewing device was used allowing stitches to be placed through a 2.8 mm accessory channel to any predetermined depth. New methods allowed knot-tying and thread-cutting through the 2.8 mm channel of the echo-endoscope. Stitches were placed through the gastric wall into the MAL and one just beyond the wall of the lower esophageal sphincter (LES). They were tied together and locked against the gastric wall. Preoperative manometry showed a median LES pressure of 11 mm/Hg and 21 mm/Hg after stitch placement (p = 0.0028). The length of the LES increased from median 2.8 cm pre-procedure to 3.5 cm post-procedure. At post mortem, the force to pull the tags out of the MAL was 2.8 kg median. This study shows that transgastric gastro-esophageal reflux surgery using stitching under EUS control can significantly increase the lower oesophageal sphincter pressure in pigs.


High-Resolution QTOF-MRM for Highly Accurate Identification and Quantification of Trace Levels of Triterpenoids in Ganoderma lucidum Mycelium.
The accurate quantification of triterpenoids in Ganoderma lucidum mushroom in the mycelium stage is challenging due to their low concentrations, interference from other possible isomers, and the complex matrix. Here, a high-resolution quadrupole-time-of-flight mass spectrometry "multiple reaction monitoring" with target enhancement (HR-QTOF-MRM) method was developed to quantify seven target triterpenoids in G. lucidum. The performance of this method was compared against an optimized QQQ-MRM method. The HR-QTOF-MRM was shown to be capable of distinguishing target triterpenoids from interferent peaks in the presence of matrices. The HR-QTOF-MRM LOD and LLOQ values were found to be one to two times lower than those derived from the QQQ-MRM method. Intraday and interday variabilities of the HR-QTOF-MRM demonstrated better reproducibility than the QQQ-MRM. In addition, excellent recoveries of the analytes ranging from 80 to 117% were achieved. Spiking experiments were carried out to verify and compare the quantitative accuracy of the two methods. The HR-QTOF-MRM method provided better percent accuracy, ranging from 84% to 99% (<3% RSD), compared with the range of 69 to 114% (<4%RSD) given by the QQQ-MRM method. These results demonstrate that the new HR-QTOF-MRM mode is able to improve sensitivity, reproducibility, and accuracy of trace level analysis of triterpenoids in the complex biological samples. The triterpenoid concentrations were in the range of nondetect to 0.06-6.72 mg/g of dried weight in fruiting body and to 0.0009-0.01 mg/g of dried weight in mycelium.


An HIV intervention tailored for black young men who have sex with men in the House Ball Community.
Black young men who have sex with men (BYMSM) are the group most disproportionately impacted by HIV in the USA and most in need of efficacious interventions to address community-level factors that increase their vulnerability to HIV. The House Ball Community (HBC) is a distinct social network within the larger BYMSM community that may be particularly vulnerable to social norms and stigma around HIV. This study tailored an evidence-based, community-level popular opinion leader (OL) intervention for use within the HBC. The intervention, called Promoting Ovahness through Safer Sex Education (POSSE), was then piloted to evaluate feasibility, acceptability, and preliminary efficacy. Recruiting OLs from the community and training them to deliver risk reduction messages were found to be feasible and highly acceptable. Community-level surveys (n = 406) were completed over five waves of data collection. Overall exposure to the intervention increased across waves. Statistically significant (p < .05) declines were observed for multiple sexual partners, condomless anal intercourse with any male partners, and with male partners of unknown HIV status. HIV stigma declined as well, but the trend was not statistically significant.


[DIGITAL DESIGN OF STANDARD PARTS DATABASE FOR PROXIMAL TIBIA FRACTURES TREATED WITH PLATING VIA THREE-DIMENSIONAL PRINTING].
To explore the method and feasibility of digital internal fixation for proximal tibia fractures using standard parts database and three-dimensional (3D) printing technology. Ten adult lower extremity specimens were selected to take continuously thin-layer scanning. After Dicom image was imported into the Mimics software, the model of Schatzker II-VI types proximal tibia fracture was established, 2 cases each type. The virtual internal fixation was performed with plate and screw from standard parts database. The pilot hole of the navigation module design was printed by 3D printing technique. The plate and screw were inserted by the navigation module. X-ray film and CT were taken postoperatively to observe the position. Thirty patients with proximal tibia fracture underwent digital internal fixation using standard parts database and 3D printing technology (study group), and another 30 patients underwent traditional open reduction and internal fixation (control group). There was no significant difference in sex, age, side, causes, fracture classification, associated injury, and course of disease between 2 groups (P > 0.05). The preparative time, incision length, fracture healing time, operation time, and intraoperative blood loss were recorded. Follow up of imaging evaluation, clinical efficacy was evaluated by MacNab criteria. The navigation models were designed to fit the bony structure of proximal tibia and to guide implant insertion. The parameters of orientation, length, diameter, and angle were consistent with the preoperative plan. No statistically significant difference was found in the preparative times of pre-operation between 2 groups (t = 1.393, P = 0.169). The incision length, wound healing time, blood loss, operation time, and the cost of treatment in study group were significantly less than those in control group (P < 0.05). All patients were followed up 12-16 months (mean, 13.5 months). The fracture healing time of study group was significantly shorter than that of control group (t = 4.070, P = 0.000). At 12 months postoperatively, there was no significant difference in the efficacy based on MacNab criteria between 2 groups (U = 377.000, P = 0.238). Digital internal fixation for proximal tibia fractures using standard parts database and 3D printing technology has the advantages of short process, less blood loss, high safety and rapid fracture healing.


Placental cartography of NADPH oxidase (NOX) family proteins: Involvement in the pathophysiology of preeclampsia.
The placenta is an essential organ for fetal development. During the first trimester, it undergoes dramatic changes as it develops in an environment poor in oxygen (around 2-3%). From about 10 gestational weeks, oxygen levels increase to 8% in the intervillous chamber. These changes are accompanied by modulation of the activity of NADPH oxidase, a major source of production of reactive oxygen species in the first trimester of pregnancy. The NOX complex is composed of seven different proteins (NOX1-5 and DUOX1-2) whose placental involvements during physiological and pathological pregnancies are largely unknown. The aim of the study was to produce a cartography of NOX family proteins, in terms of RNA, protein expression, and localization during physiological pregnancy and in the case of preeclampsia (PE), in a cohort of early-onset PE (n = 11) and late-onset PE (n = 7) cases. NOX family proteins were mainly expressed in trophoblastic cells (NOX4-5, DUOX1) and modulated during physiological pregnancy. NOX4 underwent an unexpected and hitherto unreported nuclear translocation at term. In the case of PE, two groups stood out: NOX1-3, superoxide producers, were down-regulated (p < 0.05) while NOX4-DUOX1, hydrogen peroxide producers, were up-regulated (p < 0.05), compared to the control group. Mapping of placental NOX will constitute a reference and guide for future investigations concerning its involvement in the pathophysiology of PE.


Memory deficits with intact cognitive control in the methylazoxymethanol acetate (MAM) exposure model of neurodevelopmental insult.
Cognitive impairments are amongst the most debilitating deficits of schizophrenia and the best predictor of functional outcome. Schizophrenia is hypothesized to have a neurodevelopmental origin, making animal models of neurodevelopmental insult important for testing predictions that early insults will impair cognitive function. Rats exposed to methylazoxymethanol acetate (MAM) at gestational day 17 display morphological, physiological and behavioral abnormalities relevant to schizophrenia. Here we investigate the cognitive abilities of adult MAM rats. We examined brain activity in MAM rats by histochemically assessing cytochrome oxidase enzyme activity, a metabolic marker of neuronal activity. To assess cognition, we used a hippocampus-dependent two-frame active place avoidance paradigm to examine learning and spatial memory, as well as cognitive control and flexibility using the same environment and evaluating the same set of behaviors. We confirmed that adult MAM rats have altered hippocampal morphology and brain function, and that they are hyperactive in an open field. The latter likely indicates MAM rats have a sensorimotor gating deficit that is common to many animal models used for schizophrenia research. On first inspection, cognitive control seems impaired in MAM rats, indicated by more errors during the two-frame active place avoidance task. Because MAM rats are hyperactive throughout place avoidance training, we considered the possibility that the hyperlocomotion may account for the apparent cognitive deficits. These deficits were reduced on the basis of measures of cognitive performance that account for motor activity differences. However, though other aspects of memory are intact, the ability of MAM rats to express trial-to-trial memory is delayed compared to control rats. These findings suggest that spatial learning and cognitive abilities are largely intact, that the most prominent cognitive deficit is specific to acquiring memory in the MAM neurodevelopmental model, and that hyperactivity can confound assessments of cognition in animal models of mental dysfunction.


National survey on outbreaks associated with whirlpool spas.
A national survey of state epidemiologists sought information on reported outbreaks of illness associated with non-residential whirlpool spas for the period April 1972-July 1, 1982. Reports were received from 49 states. Of the 74 whirlpool-associated outbreaks reported, 72 were characterized as having patients with papular or pustular rash and two were associated with cases of Pontiac fever.


Facility implementation and comparative performance evaluation of probe-corrected TEM/STEM with Schottky and cold field emission illumination.
We report the installation and performance evaluation of a probe aberration-corrected high-resolution JEOL JEM-ARM200F transmission electron microscope (TEM). We provide details on construction of the room that enables us to obtain scanning transmission electron microscope (STEM) data without any evident distortions/noise from the external environment. The microscope routinely delivers expected performance. We show that the highest STEM spatial resolution and energy resolution achieved with this microscope are 0.078 nm and 0.34 eV, respectively. We report a direct comparative evaluation of the performance of this microscope with a Schottky thermal field-emission gun versus a cold field-emission gun. Cold field-emission illumination improves spatial resolution of the high current probe for analytical spectroscopy, the TEM information limit, and the electron energy resolution compared to the Schottky thermal field-emission source.


Application of agents active at the alpha 2-adrenoceptor of fat cells to the treatment of obesity--a critical appraisal.
The extent of cyclic AMP (cAMP) mediated lipolysis in adipose tissue cells of man and several other animal species is regulated by the interplay of alpha- and beta-adrenoceptors modulating adenyl cyclase activity. Although the naturally-occurring catecholamines, and isoprenaline, are thought to act at the same pro-lipolytic beta-adrenoceptor antilipolytic agents, working through the alpha 2-adrenoceptor moiety of adenyl cyclase, appear to act at separate sites for: true alpha 2-agonists such as clonidine, for adenosine and for prostaglandins. Further, such antilipolytic agents are conspicuously more potent against lipolysis stimulated by methyl-isobutylxanthine (MIX) than against that stimulated by catecholamines. The nature of the dual character of adenyl cyclase remains to be elucidated. alpha 2 Adrenoceptor antagonists which promote lipolysis, and may possibly serve a therapeutic role in the treatment of obesity, may also provoke inappropriate insulin release which is contraindicated. Thus a problem in chemotherapy exists which may be resolved by new agents with differential tissue specificities. An example of this chemotherapeutic dilemma is possibly provided by the body weight accruing actions of tricyclic antidepressant compounds whose mechanism of action involves also (central) alpha 2-adrenoceptors.


Energy-landscape-model analysis for irreversibility and its pulse-width dependence in cells subjected to a high-intensity ultrashort electric pulse.
We provide a simple, but physical analysis for cell irreversibility and apoptosis in response to an ultrashort (nanosecond), high-intensity electric pulse. Our approach is based on an energy landscape model for determining the temporal evolution of the configurational probability function p(q). The primary focus is on obtaining qualitative predictions of a pulse width dependence to apoptotic cell irreversibility that has been observed experimentally. The analysis couples a distributed electrical model for current flow with the Smoluchowski equation to provide self-consistent, time-dependent transmembrane voltages. The model captures the essence of the experimentally observed pulse-width dependence, and provides a possible physical picture that depends only on the electrical trigger. A number of interesting features are predicted.


A high-fidelity method for genomic sequencing of single somatic cells reveals a very high mutational burden.
Postzygotic mutations in somatic cells lead to genome mosaicism and can be the cause of cancer, possibly other human diseases and aging. Somatic mutations are difficult to detect in bulk tissue samples. Here, we review the available assays for measuring somatic mutations, with a focus on recent single-cell, whole genome sequencing methods. Impact statement Somatic mutations cause cancer, possibly other diseases and aging. Yet, very little is known about the frequency of such mutations in vivo, their distribution across the genome, and their possible functional consequences other than cancer. Even in cancer, we do not know the heterogeneity of mutations within a tumor and if seemingly normal cells in its surroundings already have elevated mutation frequencies. Here, we review a new, whole genome amplification system that allows accurate quantification and characterization of single-cell mutational landscapes in human cells and tissues in relation to disease.


The δ18 O and δ2 H of water in the leaf growth-and-differentiation zone of grasses is close to source water in both humid and dry atmospheres.
The oxygen and hydrogen isotope composition of water in the leaf growth-and-differentiation zone, LGDZ, (δ18 OLGDZ , δ2 HLGDZ ) of grasses influences the isotopic composition of leaf cellulose (oxygen) and wax (hydrogen) - important for understanding (paleo)environmental and physiological information contained in these biological archives - but is presently unknown. This work determined δ18 OLGDZ and δ2 HLGDZ , 18 O- and 2 H-enrichment of LGDZ (∆18 OLGDZ and ∆2 HLGDZ ), and the 18 O- and 2 H-enrichment of leaf blade water (∆18 OLW, ∆2 HLW ) in two C3 and three C4 grasses grown at high and low vapor pressure deficit (VPD). The proportion of unenriched water (px ) in the LGDZ ranged from 0.9 to 1.0 for 18 O and 1.0 to 1.2 for 2 H. VPD had no effect on the proportion of 18 O- and 2 H-enriched water in the LGDZ, and species effects were small or nonsignificant. Deuterium discrimination caused depletion of 2 H in LGDZ water, increasing (apparent) px -values > 1.0 in some cases. The isotopic composition of water in the LGDZ was close to that of source water, independent of VPD and much less enriched than previously supposed, but similar to reported xylem water in trees. The well-constrained px will be useful in future investigations of oxygen and hydrogen isotopic fractionation during cellulose and wax synthesis, respectively.


[Dynamic monitoring of serum pepsinogen among high risk populations of gastric cancer in Zhuanghe county].
To investigate the dynamic changes of serum pepsinogen (PG) among the high risk populations of gastric cancer. Peripheral blood samples were collected from 444 subjects in the high risk areas of gastric cancer in Zhuanghe county, Liaoning province, who underwent screening of gastric cancer, 225 males and 219 females, aged 48.31 (21 - 76). ELISA was used to measure the serum PG I and PG II. The PG I/II ratio was calculated. Gastroscopy was conducted to take 4 pieces of biopsy specimens from each subject to undergo pathological examination. Histological examination and serum Hp-IgG antibody determination by ELISA were performed to detect the infection of Helicobacter pylori (Hp). The above mentioned examinations were carried out at the first screening and 6, 12, and 30 months later during follow-up. (1) In the age group 51 - 60, the percentage change in PG II of 6-month follow-up was 0.84, significantly lower than those of the 12-month follow-up (1.22, P = 0.019) and 30-month follow-up (1.24, P = 0.004), and the percentage change in PG I/II of the 6-month follow-up was 1.09, significantly higher than those of the 12-month follow-up (0.75, P = 0.027) and 30-month follow-up (0.69, P = 0.001). However, there were no significant differences in serum PG I, serum PG II, and PG I/II ratio in other age groups. (2) The percentage change in serum PG I of the patients of superficial gastritis (SG) with mitigation of the 6-month follow-up was 0.69, significantly lower than that of the 12-month follow-up (0.97, P = 0.002). The percentage change in PG I/II of the patients of atrophic gastritis (AG) with mitigation of the 6-month follow-up was 1.13, significantly higher than that of the 12-month follow-up (0.75, P = 0.042). (3) The percentage change in PG I of the SG-->NOR (normal) group was 0.94, significantly higher than that of the SG-->AG group (0.79, P = 0.002). The percentage changes in PG I and PG II of the AG-->NOR group were 0.43 and 0.60 respectively, both significantly lower than those of the AG-->SG group (0.87, P = 0.000, and 1.11, P = 0.010). (4) The percentage change in PG I of the Hp negative-->Hp positive group was 0.94, significantly higher than that of the Hp negative-->Hp negative group (0.81, P = 0.026). The percentage changes in PG I and PG II of the Hp positive-->Hp negative group were 0.74 and 0.86 respectively, both significantly lower than those of Hp positive-->Hp positive group (0.93 and 1.15 respectively, both P = 0.000), and the percentage change in PG I/II of the Hp positive-->Hp negative group was 0.90, significantly higher than that of the Hp positive-->Hp positive group (0.70, P = 0.022). The percentage change of serum PG is correlated with time of follow-up, feature of stomach disease, and status of Hp infection. Dynamic detection of serum PG can be applied in monitoring the populations in high risk area of gastric cancer.


Brownian dynamics study of flux ratios in sodium channels.
Measurements of unidirectional fluxes in ion channels provide one of the experimental methods for studying the steps involved in ion permeation in biological pores. Conventionally, the number of ions in the pore is inferred by fitting the ratio of inward and outward currents to an exponential function with an adjustable parameter known as the flux ratio exponent. Here we investigate the relationship between the number of ions in the pore and the flux ratio exponent in a model sodium channel under a range of conditions. Brownian dynamics simulations enable us to count the precise number of ions in the channel and at the same time measure the currents flowing across the pore in both directions. We show here that the values of the flux ratio exponent n' ranges between 1 and 3 and is highly dependent on the ionic concentrations in which measurements are made. This is a consequence of the fact that both inward and outward currents are susceptible to saturation with increasing concentration. These results indicate that measurements of the flux ratio exponent cannot be directly related to the number of ions in the pore and that interpretation of such experimental measurements requires careful consideration of the conditions in which the study is made.


Surveillance Indicators for Women's Preconception Care.
Background: Limited surveillance of preconception care (PCC) impedes states' ability to monitor access and provision of quality PCC. In response, we describe PCC indicators and the evaluation process used to identify a set of PCC indicators for state use. Materials and Methods: The Surveillance and Research Workgroup and Clinical Workgroup of the National Preconception Health and Health Care Initiative used a systematic process to identify, evaluate, and prioritize PCC indicators from nationwide public health surveillance systems that Maternal and Child Health (MCH) programs can use for state-level surveillance using the Pregnancy Risk Assessment Monitoring System (PRAMS) and Behavioral Risk Factor Surveillance System (BRFSS). For each indicator, we assessed target population, prevalence, measurement simplicity, data availability, clinical utility, and whether it was related to the 10 prioritized preconception health indicators. We also assessed relevance to clinical recommendations, Healthy People (HP)2020 objectives, and the National Quality Forum measures. Lastly, we considered input from stakeholders and subject matter experts. Results: Eighty potential PCC indicators were initially identified. After conducting evaluations, obtaining stakeholder input, and consulting with subject matter experts, the list was narrowed to 30 PCC indicators for states to consider using in their MCH programs to inform the need for new strategies and monitor programmatic activities. PRAMS is the data source for 27 of the indicators, and BRFSS is the data source for three indicators. Conclusions: The identification and evaluation of population-based PCC indicators that are available at the state level increase opportunities for state MCH programs to document, monitor, and address PCC in their locales.


Frequency of borderline personality disorder among psychiatric outpatients in Shanghai.
The objective of this study was to investigate the frequency, clinical characteristics, and comorbidity of borderline personality disorder (BPD) among psychiatric outpatients in two clinics at Shanghai Mental Health Center. A cross-sectional investigation was conducted. From 3,075 outpatients screened using the Personality Diagnostic Questionnaire-IV+, 2,284 patients positive for a personality disorder were assessed using the Structured Clinical Interview for DSM-IV Personality Disorders. The frequency of BPD among the psychiatric outpatients was 5.8%, with a frequency of 3.5% among males and 7.5% among females (p < .01). BPD was found to have extensive comorbidity with Axis I and II disorders. This study proves that BPD does occur in China. The detected frequency among outpatients is lower than that reported in North America.


The E3 ubiquitin ligases HOIP and cIAP1 are recruited to the TNFR2 signaling complex and mediate TNFR2-induced canonical NF-κB signaling.
Tumor Necrosis Factor (TNF) is a proinflammatory cytokine that elicits its action by binding to two cell surface TNF receptors (TNFR), TNFR1 and TNFR2, which are expressed by many different cell types. Stimulation of TNFR1 activates canonical NF-κB signaling, leading to the NF-κB dependent expression of a large number of genes. Canonical NF-κB signaling requires the assembly of a TNFR1 signaling complex at the cell membrane, whose formation is regulated by different protein ubiquitination events. In this context, recruitment of the Linear Ubiquitin Chain Assembly Complex (LUBAC) to TNFR1 plays an important role by mediating M1-linked polyubiquitination of specific NF-κB signaling proteins. In contrast to TNFR1, much less is known about the role of ubiquitination in TNFR2 signaling. Here we demonstrate that specific TNFR2 stimulation rapidly triggers M1- and K63-linked polyubiquitination at the TNFR2 signaling complex. In agreement, TNFR2 stimulation induces the recruitment of HOIP, a LUBAC component and the only known E3 ubiquitin ligase for M1-polyubiquitination, to the TNFR2 signaling complex. Also cIAP1, a E3 ubiquitin ligase able to modify proteins with K63-polyubiquitin chains, was recruited to the TNFR2 signaling complex. Treatment of cells with a cIAP antagonist inhibited the recruitment of HOIP and prevented HOIP-mediated M1-ubiquitination of the TNFR2 signaling complex, indicating that HOIP recruitment to the TNFR2 relies on cIAPs. Finally, we show that both HOIP and cIAP1 are required for TNFR2-induced canonical NF-κB activation. Together, our findings demonstrate an important role for M1- and K63-linked polyubiquitination in TNFR2 signaling.


A microfluidic chip for visual investigation of the interaction of nanoemulsion of Satureja Khuzistanica essential oil and a model gram-negative bacteria.
Nanotechnology has provided novel approaches against food born and pathogenic bacteria. Within the present study, the effects of pure and nanoemulsified essential oil derived from Satureja Khuzistanica essential oil (SKEO) on Escherichia coli (E. coli ATCC 25922) as a human pathogen has been studied using a microfluidic chip. The morphology and antibacterial activity of E. coli at disparate residence durations (from 2 to 30 min) and various nanoemulsified or pure essential oil concentrations (8.0-62.5 μg mL-1) and numerous nanoemulsion's droplet sizes from 32 to 124 nm, have been investigated in the microfluidic system. Also, the quantitative analysis including optical density, time killing assay, protein, nucleic acid and potassium release were employed to confirm the effects of bacterial inhibition taking advantage of the chip apparatus. It was revealed that the prepared nanoemulsion left a considerable destructive effect on E. coli bacterial membrane, confirmed by fast release of cytoplasmic elements including protein, nucleic acid and potassium. However, this process was remarkably intensified for both nanoemulsion and pure essential oil using the microfluidic chip versus the conventional methods. The results also revealed that after 4 min of bacterium treatment by 12.5 μg mL-1 nanoemulsion with 32 nm mean particle size, the bacterial membrane wall began to degrade rapidly, and bacterial activity was almost completely inhibited in a 20-min period. These findings may have implications in the similarly structured and phospholipid-encapsulated bacteria and viruses, like COVID-19.


Awareness of Polish undergraduate and graduate students regarding the impact of viral infections and high-risk sexual behaviors on the occurrence of oral cancer.
With every passing year, more and more studies and observations demonstrate growing incidence of oral cancer, a decrease in patients' age, and an increasing number of epidemiological factors. The aim of the study was to determine the level of awareness among undergraduate and graduate university students regarding the incidence of oral cancer linked with viral infections and high-risk sexual behavior, including oral sex. Self-administered questionnaire-based survey was carried out among 196 Polish students aged 19 to 25 years. It was found that the young adults understood the meaning of human papillomavirus (HPV), but associated it only with the squamous cell carcinoma of the cervix. A total of 43.4% did not realize that there was any correlation between HPV infection and the development of oral cancer. The students who were aware of this correlation constituted 40.3% of the total. The majority of the participants, that is, 82 subjects (41.8%), did not associate the occurrence of malignant neoplasms of the oral cavity with oral sex. The study group did not present adequate awareness of the fact that occurrence of oral cancer may be associated with high-risk sexual behaviors. Knowledge of oral cancer was not significantly related to the level of university education (P < .005).


Sleep quality predicts quality of life and mortality risk in haemodialysis patients: results from the Dialysis Outcomes and Practice Patterns Study (DOPPS).
Poor sleep quality (SQ) affects many haemodialysis (HD) patients and could potentially predict their morbidity, mortality, quality of life (QOL) and patterns of medication use. Data on SQ were collected from 11,351 patients in 308 dialysis units in seven countries in the Dialysis Outcomes and Practice Patterns Study (DOPPS) between 1996 and 2001 through a patient self-reported SQ scale, ranging from 0 (worst) to 10 (best). A score of <6 reflected poor SQ. Sleep disturbance was also assessed by self-reported daytime sleepiness, feeling drained and nocturnal awakening. Logistic and multiple linear regression were used to assess predictors of SQ and associations with QOL. Cox regression examined associations with mortality. Analyses accounted for case-mix, facility clustering and country. Nearly half (49%) of patients experienced poor SQ. Mean SQ scores varied by country, ranging from 4.9 in Germany to 6.5 in Japan. Patients with poor SQ were more likely to be prescribed antihistamines, antidepressants, anti-inflammatories, narcotics, gastrointestinal (GI) medications, anti-asthmatics or hypnotics. Physical exercise at least once a week (vs < once a week) was associated with lower odds of poor SQ (AOR = 0.55-0.85, P < 0.05). Poorer SQ was associated with significantly lower mental and physical component summary (MCS/PCS) scores (MCS scores 1.9-13.2 points lower and PCS scores 1.5-7.7 points lower when SQ scores were <10 vs 10). The RR of mortality was 16% higher for HD patients with poor SQ. Poor SQ is common among HD patients in DOPPS countries and is independently associated with several QOL indices, medication use patterns and mortality. Assessment and management of SQ should be an important component of care.


[The nasolabial cyst].
The authors present the clinical observation of the nasolabial cyst together with the concise overview of the relevant literature and terminology, etiology and pathogenesis of this condition.


Recent Developments in the Treatment of Spinal Epidural Abscesses.
Spinal epidural abscess (SEA) is a serious condition that can be challenging to diagnose due to nonspecific symptomology and delayed presentation. Despite this, it requires prompt recognition and management in order to prevent permanent neurologic sequelae. Several recent studies have improved our understanding of SEA. Herein, we summarize the recent literature from the past 10 years relevant to SEA diagnosis, management and outcome. While surgical care remains the mainstay of treatment, a select subset of SEA patients may be managed without operative intervention. Multidisciplinary management involves internal medicine, infectious disease, critical care, and spine surgeons in order to optimize care.


Range of motion studies for total hip replacements. A comparative study with a new experimental apparatus.
Significant differences in ROM exist between different THR prosthesis designs: several of the prosthesis designs tested are marginal in flexion; several millimeters of socket wear will decrease the ROM. The results also emphasize the importance of proper component orientation at surgery. The surgeon has less latitude in orienting the components of a THR with limited ROM. Subluxation and dislocation due to rim contact can be minimized with most prosthetic units by instructing the patients to abduct and/or externally rotate their hips during acute flexion. Analyses suggest that impingement of prosthesis neck and socket rim may lead to increased risk of dislocation and increased rim wear. Prostheses with adequate ROM for everyday activities should provide stability, less frequent neck and socket contact with decreased rim wear, less force transmission to acrylic-bone interface, and less diminution of ROM with wear of the socket wall.


Automated facial image analysis: detecting improvement in abnormal facial movement after treatment with botulinum toxin A.
The purpose of this study was to evaluate the ability of Automated Facial Image Analysis (AFA) to detect changes in facial motion after Botox injections in patients with facial nerve disorders accompanied by abnormal muscle activity. Eight subjects received Botox for oral to ocular synkinesis (n = 6), ocular to oral synkinesis (n = 1), and/or depressor anguli oris overactivity (n = 3). Subjects were video-recorded during 2 directed facial action tasks before and after Botox treatment. AFA measurement and Facial Grading System (FGS) scores were used to evaluate the effects of Botox. After Botox, AFA detected a decrease in abnormal movements of the eyelids in all patients with oral to ocular synkinesis, a decrease in oral commissure movement for the patients with ocular to oral synkinesis, and an increase in oral commissure movement in all patients with depressor overactivity. The FGS scores failed to demonstrate any change in facial movement for the case of ocular to oral synkinesis and for 2 cases of depressor overactivity. AFA enables recognition of subtle changes in facial movement that may not be adequately measured by observer based ratings of facial function.


Human infective endocarditis caused by Streptococcus suis serotype 2.
Human infective endocarditis due to Streptococcus suis occurs infrequently. The case of a 43-year-old male who sustained life-threatening infective endocarditis is reported. Since growth of S. suis on commonly used sheep blood agar plates resembles viridans streptococci, diagnosis of S. suis constitutes a diagnostic pitfall. Identification was accomplished by using molecular methods.


Study of Modified Area of Polymer Samples Exposed to a He Atmospheric Pressure Plasma Jet Using Different Treatment Conditions.
In the last decade atmospheric pressure plasma jets (APPJs) have been routinely employed for surface processing of polymers due to their capability of generating very reactive chemistry at near-ambient temperature conditions. Usually, the plasma jet modification effect spans over a limited area (typically a few cm²), therefore, for industrial applications, where treatment of large and irregular surfaces is needed, jet and/or sample manipulations are required. More specifically, for treating hollow objects, like pipes and containers, the plasma jet must be introduced inside of them. In this case, a normal jet incidence to treated surface is difficult if not impossible to maintain. In this paper, a plasma jet produced at the end of a long flexible plastic tube was used to treat polyethylene terephthalate (PET) samples with different incidence angles and using different process parameters. Decreasing the angle formed between the plasma plume and the substrate leads to increase in the modified area as detected by surface wettability analysis. The same trend was confirmed by the distribution of reactive oxygen species (ROS), expanding on starch-iodine-agar plates, where a greater area was covered when the APPJ was tilted. Additionally, UV-VUV irradiation profiles obtained from the plasma jet spreading on the surface confirms such behavior.


[X-linked adrenoleukodystrophy with an atypical radiological pattern].
X-linked adrenoleukodystrophy (X-ALD) is the most frequent peroxisomal disease. It is due to a mutation in the ABCD1 gene. The loss of functioning of ABCD1 triggers ineffective beta oxidation of very long-chain fatty acids, which gives rise to an accumulation of these fatty acids. The typical alteration revealed in neuroimaging scans in the cerebral form is symmetrical periventricular demyelination with posterior location. We report the case of a 10-year-old boy with right spastic hemiparesis and subacute cognitive impairment. Magnetic resonance imaging of the brain showed symmetrical involvement of the white matter in the left frontoparietotemporal region, and calcifications were observed in the computerised axial tomography scan. X-ALD was confirmed by means of the elevated levels of very long-chain fatty acids, and a pathogenic variant was found in the ABCD1 gene. Symmetrical demyelination with calcifications has rarely been reported in X-ALD, and these findings could delay diagnosis. This exceptional presentation should always be taken into consideration in children with subacute onset of motor symptoms and cognitive or behavioural regression.


Color Doppler Ultrasound and Hemodynamics for Evaluating Graft Dysfunction in Recurrent Immunoglobulin A Nephropathy.
BACKGROUND The aim of this study was to investigate the diagnostic and prognostic utility of color Doppler ultrasound for graft dysfunction in recurrent immunoglobulin A nephropathy (IgAN). MATERIAL AND METHODS We selected a series of 78 biopsies diagnostic of recurrent IgAN following living-donor transplantation from July 2004 to January 2019. Based on Lee's classification, Doppler parameters in different degrees of histopathological injury were retrospectively analyzed. RESULTS The 4-year cumulative graft survival rate after biopsy was 66.3%, and the difference among the Kaplan-Meier curves of Lee's classification (P<0.01) was significant. Doppler parameters showed that echo enhancement, decreasing blood flow distribution, decreasing end-diastolic velocity (EDV) of the main renal artery (MRA), segmental renal atery (SRA) and interlobar renal artery (IRA), and an elevated resistance index (RI) of the arcuate renal artery (ARA) were significantly different among grades I-V of Lee's classification (P<0.05). Logistic multivariate analysis indicated that echo enhancement (HR 13.6, 95% CI 2.7-68.4) and decreasing EDV of the SRA (HR 1.1 for a 1-cm/s, 95% CI 1.0-1.2) were independent predictors of severe injury (IV-V). The ROC curve fitted by echo enhancement and decreasing EDV of the SRA had an area under the curve of 0.87. The cutoff was 17.5 cm/s (decreasing EDV of the SRA) without echo enhancement. The sensitivity and specificity were 72.2% and 91.7%, respectively. CONCLUSIONS Color Doppler ultrasound successfully evaluated the graft dysfunction in recurrent IgAN; a decreasing EDV of the SRA indicated severe histopathological injury and poor prognosis.


Hyperprolactinemia does not influence hypothalamic-pituitary-adrenocortical function during hypoglycemia in women.
Elevated plasma prolactin and mild hypocortisolemia have been observed in patients with rheumatic disorders. This study was designed to assess the potential inhibitory effect of hyperprolactinemia on hypothalamic-pituitary-adrenocortical function. Hypoglycemia was induced by intravenous insulin injection (0.1 IU/kg) in 10 female volunteers of fertile age during their follicular phase twice: 60 min after either domperidone (10 mg orally) or placebo administration. Blood samples were collected from an indwelling catheter inserted into the cubital vein at -60, 0, 30, 45, 60 and 90 min. The concentrations of prolactin, adrenocorticotropic hormone (ACTH), cortisol, epinephrine, norepinephrine and glucose were measured in plasma. Domperidone administration significantly increased plasma prolactin concentrations (71 +/- 11 ng/ml vs. 14 +/- 6 ng/ml; p <0.001), while basal plasma concentrations of ACTH, cortisol, norepinephrine and epinephrine were unaffected. Insulin-induced hypoglycemia resulted in a significant rise in the mean plasma ACTH levels from 10 +/- 1 pg/ml (domperidone) and 11 +/- 1 pg/ml (controls) to 148 +/- 19 pg/ml (domperidone) and 139 +/- 12 pg/ml (controls) at 45 min (p < 0.001), in plasma cortisol from 407 +/- 62 nmol/l (domperidone) and 391 +/- 42 nmol/l (controls) to 925 +/- 60 nmol/l (domperidone) and 810 +/- 52 nmol/l (controls) at 60 min (p < 0.001), and in plasma epinephrine from 40 +/- 26 pg/ml (domperidone) and 16 +/- 3 pg/ml (controls) to 274 +/- 55 pg/ml (domperidone) and 352 +/- 61 pg/ml (controls) at 30 min; (p < 0.001). The significant increase in ACTH, cortisol and epinephrine responses to hypoglycemia was similar in both groups. We observed mild norepinephrine response to hypoglycemia but this was irrespective of the medication. In conclusion, pharmacologically-induced hyperprolactinemia did not induce significant changes of hypothalamic-pituitary-adrenocortical function and did not influence sympathoadrenal activity in healthy young women.


Glutamine substitution at alanine1649 in the S4-S5 cytoplasmic loop of domain 4 removes the voltage sensitivity of fast inactivation in the human heart sodium channel.
Normal activation-inactivation coupling in sodium channels insures that inactivation is slow at small but rapid at large depolarizations. M1651Q/M1652Q substitutions in the cytoplasmic loop connecting the fourth and fifth transmembrane segments of Domain 4 (S4-S5/D4) of the human heart sodium channel subtype 1 (hH1) affect the kinetics and voltage dependence of inactivation (Tang, L., R.G. Kallen, and R. Horn. 1996. J. Gen. Physiol. 108:89-104.). We now show that glutamine substitutions NH2-terminal to the methionines (L1646, L1647, F1648, A1649, L1650) also influence the kinetics and voltage dependence of inactivation compared with the wild-type channel. In contrast, mutations at the COOH-terminal end of the S4-S5/D4 segment (L1654, P1655, A1656) are without significant effect. Strikingly, the A1649Q mutation renders the current decay time constants virtually voltage independent and decreases the voltage dependences of steady state inactivation and the time constants for the recovery from inactivation. Single-channel measurements show that at negative voltages latency times to first opening are shorter and less voltage dependent in A1649Q than in wild-type channels; peak open probabilities are significantly smaller and the mean open times are shorter. This indicates that the rate constants for inactivation and, probably, activation are increased at negative voltages by the A1649Q mutation reminiscent of Y1494Q/ Y1495Q mutations in the cytoplasmic loop between the third and fourth domains (O'Leary, M.E., L.Q. Chen, R.G. Kallen, and R. Horn. 1995. J. Gen. Physiol. 106:641-658.). Other substitutions, A1649S and A1649V, decrease but fail to eliminate the voltage dependence of time constants for inactivation, suggesting that the decreased hydrophobicity of glutamine at either residues A1649 or Y1494Y1495 may disrupt a linkage between S4-S5/D4 and the interdomain 3-4 loop interfering with normal activation-inactivation coupling.


Intravesical foreign body: case report.
Foreign bodies of the urinary bladder may occur by self insertion or migration from the neighbouring organs. All the foreign bodies when left for long act as a nidus for calculus formation. The patient usually presents with dysuria, intermittent urinary tract infection or suprapubic pain. Here we report two cases of vesical foreign body which was removed by the cystoscopy.


[Effects on the pancreatic orthotopic transplantation tumor in nude mice by different Chinese medicine therapeutic methods].
To compare different Chinese medicine (CM) therapeutic methods on the pancreatic orthotopic transplantation tumors in nude mice, and to explore their features. The pancreatic orthotopic transplantation tumor model was established. Sixty nude mice were randomly divided into four group, i. e., the blood circulation activating and stasis resolving group, the heat clearing and dampness removing group, the Pi-strengthening and qi-regulating group, the phlegm reducing and mass resolving group, the normal control 1 group, and the normal control 2 group, 10 in each group. 0.2 mL corresponding CM decoction or normal saline was respectively administered to each group by gastrogavage, once daily, for totally 28 days. The body weight, the tumor weight, and the tumor inhibition ratio were observed. The tumor inhibition ratio was 42.69% in the heat clearing and dampness removing group, 31.24% in the blood circulation activating and stasis resolving group, 2.11% in the Pi-strengthening and qi-regulating group, and -12.95% in the phlegm reducing and mass resolving group. There was statistical difference in the tumor weight between the heat clearing and dampness removing group and the normal control 1 group (g, 0.51 +/- 0.28 vs 0.90 +/- 0.25, P < 0.05). There was no statistical difference in the body weight change between the two groups (P > 0.05). The CM pathogenesis of pancreatic carcinoma may possibly due to the accumulation of dampness and heat, or the accumulation of dampness, heat, and toxicity. Clearing heat and removing dampness may be the basic principle for its treatment.


Infectious keratitis after overnight orthokeratology in Canada.
To report 3 cases of infectious keratitis related to overnight orthokeratology use. Retrospective case observation. All 3 patients were using overnight orthokeratology lenses when they presented with unilateral corneal ulcers. The organisms isolated were Acanthamoeba, Pseudomonas aeruginosa, and Serratia marcescens. The clinical presentation and treatment of each case is presented. Overnight orthokeratology use may be associated with infectious keratitis despite the use of more oxygen-permeable materials and improved lens design. Patient education with informed consent, appropriate lens care, and meticulous follow-up is important. Because this complication is potentially sight threatening, orthokeratology requires further analysis and evaluation to establish its safety. The cases here are the first few reported cases in North America.


Cutaneous adverse effects of biologic medications.
Biologic therapies have become widely used but often cause cutaneous adverse effects. The authors discuss the cutaneous adverse effects of tumor necrosis factor (TNF) alpha inhibitors, epidermal growth factor receptor (EGFR) inhibitors, small-molecule tyrosine kinase inhibitors (TKIs), and cell surface-targeted monoclonal antibodies, including how to manage these reactions and when to refer to a dermatologist.


[The diagnostic value and possible mechanism of the dynamic characteristics of the electroencephalogram in tumors of the brain].
It was established that the trajectory of the excitative area (an increase of negativity) on the surface of the brain does not go through the place of the tumor. It either stops there during a certain period of time or makes a sharp turn, or is subjective to a splitting. In such cases the excitative area does not extend in the usual way in one direction, but speards simultaneously to opposite sides. The author discusses the possible influence of the pathological corticofugal impulsations from the perifocal zone of the tumor on the mechanism of pacemaker scanning.


TokyoGreen derivatives as specific and practical fluorescent probes for UDP-glucuronosyltransferase (UGT) 1A1.
TokyoGreen (TG) derivatives were found to be efficient and specific substrates of an important drug-metabolizing enzyme, UDP-glucuronosyltransferase (UGT) 1A1. A rapid, specific, and sensitive assay of the enzyme was achieved simply by monitoring the change in fluorescence intensity. We also designed and developed the first "turn-on" fluorescent probes for UGTs.


Oral contraceptives: relations to mammary cancer, benign breast lesions, and cervical cancer.
The results of experimental studies on the relationship of estrogens and oral contraceptives to mammary lesions demonstrate that the type of response obtained depends largely on the species and strain of animal that is employed. A variety of clinical studies has failed to demonstrate that estrogen can cause mammary cancer, this lack of effort correlates with the results obtained in various studies in animals. Similar relationships exist for oral contraceptives, and the clinical data show good agreement in demonstrating that the contraceptive steroids do not have a tumorigenic effect on the human mammary gland. Estrogen can increase the occurrence of cervical cancer in certain strains of mice, but apparently this effect is not observed in other species of animals, including man. The preponderance of data shows that oral contraceptives do not adversely affect the occurence of abnormal Papanicolaou smears, cervical dysplasia, cervical cancer in situ, or invasive cervical cancer.


A novel hexatungstate fragment stabilized by dimethyltin groups: [{(CH3)2Sn}2(W6O22)]4-.
Reaction of Na2WO4 and (CH3)2SnCl2 in water (pH 7) led to the formation of the hybrid organic-inorganic polyanion [{(CH3)2Sn}2(W6O22)]4- (1), which is composed of a novel hexatungstate core stabilized by two dimethyltin groups. Selective crystallization of 1 with guanidinium cations resulted in [C(NH2)3]4[{CH3)2Sn}2(W6O22)]2H2O (1a), which exhibits a 1D arrangement via distorted trigonal-bipyramidal cis-(CH3)2SnO3 moieties.


H-index in the Brazilian Academy of Sciences: comments and concerns.
Bibliometric parameters have been used in order to evaluate a scientist's performance. The h-index has been gradually accepted as the most adequate parameter for this purpose. To have an idea of this index among Brazilian scientists, we performed an analysis of this parameter for the full members of the Brazilian Academy of Sciences (BAS). The h-index of 402 members listed in 10 distinct categories by the BAS was determined, cross-checked with the curriculum vitae of each of them listed at the Plataforma Lattes database (CVL) and compared with each other. Despite the large production, mostly in journals without impact factor, the h-indexes among the BAS members are comparatively low and show a large variation in all of the 10 categories, particularly in Biomedical and Physical sciences. The highest average of h-index values was found in Biomedical, Health and Chemical sciences; the lowest values were found in Human sciences where this index is meaningless. Several problems due to the trend that new and "fresh" publications need be constantly produced (the "bakery-effect") are discussed. This study points to the need of developing countries such as Brazil to invest in national scientific journals in order to make them gradually part of the mainstream journals. This would have a positive effect on bibliometric parameters of Brazilian researchers, including the h-index.


Hypertonic saline resuscitation maintains a more balanced profile of T-lymphocyte subpopulations in a rat model of hemorrhagic shock.
To investigate the potential and early effect of hypertonic saline resuscitation on T-lymphocyte subpopulations in rats with hemorrhagic shock. A model of rat with severe hemorrhagic shock was established in 18 Sprague-Dawley (SD) rats. The rats were randomly divided into Sham group, HTS group (hypertonic saline resuscitation group) and NS group (normal saline resuscitation group). Each group contained 6 rats. The CD4(+) and CD8(+) subpopulations of T-lymphocytes in peripheral blood were detected respectively before shock and after resuscitation by double antibody labelling and flow cytometry. In the early stage after hemorrhagic shock, fluid resuscitation and emergency treatment, the CD4(+) lymphocytes of peripheral blood in HTS and NS groups markedly increased. Small volume resuscitation with HTS also induced peripheral CD8(+) lymphocytes to a certain extent, whereas NS resuscitation showed no effect in this respect. Consequently, compared with Sham and HTS groups, CD4(+)/CD8(+) ratio of peripheral blood in NS group was obviously increased, and showed statistically differences. In this model of rat with severe hemorrhagic shock, small volume resuscitation with HTS is more effective than NS in reducing immunologic disorders and promoting a more balanced profile of T-lymphocyte subpopulations regulating network.


Glucose intolerance in children with chronic renal failure.
Carbohydrate metabolism was studied by the hyperglycemic clamp technique in 14 children with moderate to severe chronic renal failure (CRF) (8 pubertal and 6 prepubertal) and was compared with 5 healthy prepubertal children and 7 healthy young adults. Constant hyperglycemia was maintained for 120 min. Under these conditions, the average glucose infusion rate (M) is an index of glucose metabolic rate, the average insulin response (I) is an index of beta cell responsiveness to hyperglycemia, and the M/I ratio is an index of insulin sensitivity. Children with CRF were glucose intolerant (lower M), hyperinsulinemic (higher I), and insulin resistant (lower M/I) compared with the control children. An age-related difference in glucose tolerance and insulin sensitivity was noted. Pubertal children with CRF had lower M and lower M/I compared with prepubertal children with CRF. The 7 adult controls also had lower M and lower M/I compared with the 5 children controls. M and M/I correlated with glomerular filtration rate (GFR) in the 8 pubertal children, while M/I also correlated with GFR in the 6 prepubertal children with CRF. The hyperglycemic clamp provides a useful tool in studying the pathogenesis of carbohydrate disturbances in children with CRF.


Measurement of endogenous carbon monoxide formation in biological systems.
Endogenous carbon monoxide (CO) formation has been measured in different biological systems using a variety of analytical procedures. The methods include gas chromatography-reduction gas detection, gas chromatography-mass spectroscopic detection, laser sensor-infrared absorption, UV-visible spectrophotometric measurement of CO-hemoglobin or CO-myoglobin complex, and formation of (14)CO from (14)C-heme formed following [2-(14)C]glycine administration. CO formation ranged from a low of 0.029 nmol/mg of protein/h in chorionic villi of term human placenta to a high of 0.28 nmol/mg of protein/h in rat olfactory receptor neurons in culture and rat liver perfusate.


Seroprevalence of SARS-CoV-2 Antibodies in Children and Adolescents: Results From a Population-Based Survey in 10 Colombian Cities.
Background. Understanding COVID-19 dynamics in Colombia during the first pandemic year (2020) gives important insights surrounding population's exposure risk and specific susceptibilities. Seroprevalence studies can aid in having a broader understanding of the disease, offering a more inclusive view of the pandemic's impact across the population. Methods. A population-based cross-sectional study to assess antibodies against SARS-CoV-2 in 10 Colombian cities was developed between September and December 2020. Cities were grouped according development typology (Robust (RD), Intermediate (ID) and Incipient (InD)). Detection of total antibodies (IgM + IgG) against SARS-CoV-2 was employed. Univariate Odds Ratios (OR) were estimated for antibody results and selected variables. Results. About 3124 children aged between 5 and 17 years were included. Factors related to lower seropositive results were affiliation to the employer-based health insurance in RD and ID cities (OR: 0.579, 95% CI 0.477-0.703, OR: 0.648, 95%CI 0.480-0.874 respectively) and living in a household with adequate access to public services only for ID cities (OR: 0.679. 95% CI 0.491-0.939). Higher seropositivity rates in RD and ID cities were seen in children belonging to the low socioeconomic stratum (RD: OR: 1.758, 95% CI 1.427-2.165; ID: OR: 2.288, 95% CI 1.599-3.275) and living in an overcrowded household (RD: OR: 1.846, 95% CI 1.467-2.323; ID: OR: 2.379, 95% CI 1.769-3.199). Conclusions. Children and adolescents showed substantial impact from the COVID-19 pandemic. Disadvantageous living conditions were found to be significantly related to having a positive SARS-CoV-2 antibody test. These results highlight the need to prioritize vulnerable populations in the context of health emergencies.


Bioinformatic Analysis for Potential Biomarkers and Therapeutic Targets of T2DM-related MI.
Type 2 diabetes mellitus (T2DM), a major risk factor of coronary heart disease, is associated with an approximately twofold increase in the risk of myocardial infarction (MI). We studied co-expressed genes to demonstrate relationships between DM and MI and revealed the potential biomarkers and therapeutic targets of T2DM-related MI. DM and MI-related differentially expressed genes (DEGs) were identified by bioinformatic analysis, Gene Expression Omnibus (GEO) datasets GSE42148 and GSE61144 of MI patients, and the normal control and GSE26168 and GSE15932 of DM patients and normal controls, respectively. Further target prediction and network analysis method were used to detect protein-protein interaction (PPI) networks, gene ontology (GO) terms, and pathway enrichment of DEGs. Co-expressed DEGs of T2DM-related MI were analyzed as well. We identified 210 upregulated and 127 downregulated DEGs in T2DM, as well as 264 upregulated and 242 downregulated DEGs in MI. Eighteen upregulated and four downregulated DEGs were identified as co-DEGs of T2DM and MI. Functional analysis revealed that T2DM-related DEGs were mostly enriched in the viral process and ubiquitin-mediated proteolysis, while MI-related DEGs were mostly enriched in protein phosphorylation and TNF signaling pathway. MPO, MMP9, CAMP, LTF, AZU1, DEFA4, STAT3, and PECAM1 were recognized as the hub genes of the co-DEGs with acceptable diagnostic values in T2DM and MI datasets. Adenosine receptor agonist IB-MECA was predicted to be a potential drug for T2DM-related MI with the highest CMap connectivity score. Our study identified that the co-DEGs of MPO, MMP9, CAMP, LTF, AZU1, DEFA4, STAT3, and PECAM1 are significantly associated with novel biomarkers involved in T2DM-related MI. However, more experimental research and clinical trials are demanded to verify our results.


Ion-induced gamma-ray detection of fast ions escaping from fusion plasmas.
A 12 × 12 pixel detector has been developed and used in a laboratory experiment for lost fast-ion diagnostics. With gamma rays in the MeV range originating from nuclear reactions (9)Be(α, nγ)(12)C, (9)Be(d, nγ)(12)C, and (12)C(d, pγ)(13)C, a high purity germanium (HPGe) detector measured a fine-energy-resolved spectrum of gamma rays. The HPGe detector enables the survey of background-gamma rays and Doppler-shifted photo peak shapes. In the experiments, the pixel detector produces a gamma-ray image reconstructed from the energy spectrum obtained from total photon counts of irradiation passing through the detector's lead collimator. From gamma-ray image, diagnostics are able to produce an analysis of the fast ion loss onto the first wall in principle.


What predicts improvement and compliance during the behavioral treatment of obsessive compulsive disorder?
The aim of the study was to identify factors associated with treatment compliance and clinical improvement when obsessive compulsive disorder is treated with graded exposure and response prevention. The sample consisted of all patients with a diagnosis of obsessive compulsive disorder admitted over a 3-year period to a unit specialising in behavioral treatment. All subjects were diagnosed using reliable diagnostic criteria and all were followed-up for 12 months. A range of social and clinical variables was examined using stepwise regression analysis. Treatment compliance was associated with being employed during treatment and living with one's family. Clinical improvement was associated with never having been treated previously, being employed during treatment, having a fear of contamination, having overt ritualistic behaviour, the absence of depression and living with one's family.


Patterns in Serum Toxicokinetics in Peromyscus Exposed to Per- and Polyfluoroalkyl Substances.
Per- and polyfluoroalkyl substances (PFAS) are compounds manufactured for use in paints, cleaning agents, fire suppressants, nonstick cookware, food containers, and water-resistant products. Concerns about PFAS stem from their ubiquitous presence in the environment, persistence, and variable/uncertain bioaccumulation and toxicity. In the present study, 5 perfluoroalkyl acids and one polyfluoroalkyl substance were administered to white-footed mice (Peromyscus leucopus) to elucidate the kinetics of each chemical over 28 d of exposure. Perfluorooctanoate, perfluorohexane sulfonate (PFHxS), and perfluorobutane sulfonate were administered to male and female mice via drinking water. Perfluorooctane sulfonate, perfluorononanoate, 6:2 fluorotelomer sulfonate, and PFHxS were administered to male and female mice via oral gavage. Blood samples collected after 14 or 21 and 28 d of exposure were analyzed for individual PFAS concentrations via liquid chromatography-tandem mass spectrometry. In general, a plateau in serum concentration in this toxicity test-relevant timeline depended on interactions between 1) the type of PFAS (i.e., perfluoroalkyl sulfonic acids [PFSAs] vs perfluoroalkyl carboxylic acids [PFCAs] vs polyfluorinated), 2) continuous versus bolus dosing, and 3) to a lesser extent, sex. Specifically, PFCAs were detected at higher concentration in females than males, whereas PFSAs were generally detected at similar levels across sex. An exception occurred when PFHxS yielded higher serum levels in males than females through bolus, but not continuous, dosing. Type of PFAS had the largest impact on serum concentrations, whereas sex had the lowest. As such, future work on the toxicokinetics of PFAS in common ecological receptors would be valuable to further explore these patterns. Environ Toxicol Chem 2021;40:2886-2898. © 2021 SETAC. This article has been contributed to by US Government employees and their work is in the public domain in the USA.


Stroke and thromboembolic event rates in atrial fibrillation according to different guideline treatment thresholds: A nationwide cohort study.
Contemporary guidelines suggest anticoagulant treatment decisions in atrial fibrillation (AF) patients to be based on risk stratification for stroke. However, guidelines do not agree on the threshold for treatment initiation. We explored the variation in thromboembolic event rates in a non-anticoagulated AF population, according to different guideline threshold and methodological approaches. AF patients between 1998 and 2014 free from anticoagulant treatment were identified. Event rates for ischemic stroke and ischemic stroke/systemic embolism were explored. The overall ischemic stroke rate was 3.20 per 100 person-years ('formal rate assessment'). For patients with a CHA2DS2-VASc score of 1 the ischemic stroke rate was 0.97 when using a 'formal rate assessment', 0.62 when using a 'conditioning on the future' approach, and 0.93 when using a 'censoring approach'. Rates for thromboembolism for the 'European treatment threshold' (CHA2DS2-VASc score of 1, males only) ranged 1.17 to 1.53. Rates for the 'U.S. treatment threshold' (CHA2DS2-VASc of 2) ranged from 1.95 to 2.33. Thromboembolic event rates differed markedly in non-anticoagulated AF patients according to the conflicting European and U.S. guideline treatment thresholds. Second, the choice of methodological approach has implications, thus we recommend using the censoring approach for event rate estimation among AF patients not on treatment.


Antarctic ascidians under increasing sedimentation: Physiological thresholds and ecosystem hysteresis.
Glacier melting sediment inputs affect coastal ecosystems on the Antarctic Peninsula. In Potter Cove (South Shetland Islands, Antarctica), the shift from an "ascidian dominated" to a "mixed" assemblage has been linked to sedimentation. However, in recently described newly ice-free areas ascidians became dominant in spite of total suspended particulate matter (TSPM) concentrations, which are the highest measured in Potter Cove. Here, we compared the gut content and energy reserve of three ascidian species at three stations under different TSPM regimes. All analysed species had a higher gut content with lower %OM at these newly areas. A theoretical relationship between the scope for growth for the targeted ascidians and TSPM explained assemblages' recorded change but failed to explain current ascidians distribution. The results may indicate the existence of a TSPM threshold that allows the spatial coexistence of alternative stable states at benthic Potter Cove system.


Depth of soil compaction predominantly affects rice yield reduction by reproductive-stage drought at varietal screening sites in Bangladesh, India, and Nepal.
Drought is the major constraint to rainfed rice productivity in South Asia, but few reports provide detailed characterization of the soil properties related to drought stress severity in the region. The aim of the study was to provide a compilation of drought breeding network sites and their respective levels of drought stress, and to relate soil parameters with yield reduction by drought. This study characterized levels of drought stress and soil nutrient and physical properties at 18 geographically distributed research station sites involved in rice varietal screening in Bangladesh, India, and Nepal, as well as at farmers' fields located near the research stations. Based on soil resistance to penetration profiles, a hardpan was surprisingly absent at about half of the sites characterized. Significant relationships of depth of compaction and yield reduction by drought indicated the effects of soil puddling on susceptibility to cracking, rather than water retention by hardpans, on plant water availability in this region. The main difference between research stations and nearby farmers' fields was in terms of soil compaction. These results present an initiative for understanding the range of severities of reproductive-stage drought stress in drought-prone rainfed lowland rice-growing areas in South Asia.


Subcutaneous metastasis from an occult esophageal cancer detected by PET-CT.
We describe a unique case of an occult esophageal cancer patient without any significant symptomatology, which initially presented with a subcutaneous metastasis in the thigh. Eventually, FDG PET-CT unmasked the primary tumor of unknown origin.


Chromosome structure and human immunodeficiency virus type 1 cDNA integration: centromeric alphoid repeats are a disfavored target.
Integration of retroviral cDNA into host chromosomal DNA is an essential and distinctive step in viral replication. Despite considerable study, the host determinants of sites for integration have not been fully clarified. To investigate integration site selection in vivo, we used two approaches. (i) We have analyzed the host sequences flanking 61 human immunodeficiency virus type 1 (HIV-1) integration sites made by experimental infection and compared them to a library of 104 control sequences. (ii) We have also analyzed HIV-1 integration frequencies near several human repeated-sequence DNA families, using a repeat-specific PCR-based assay. At odds with previous reports from smaller-scale studies, we found no strong biases either for or against integration near repetitive sequences such as Alu or LINE-1 elements. We also did not find a clear bias for integration in transcription units as proposed previously, although transcription units were found somewhat more frequently near integration sites than near controls. However, we did find that centromeric alphoid repeats were selectively absent at integration sites. The repeat-specific PCR-based assay also indicated that alphoid repeats were disfavored for integration in vivo but not as naked DNA in vitro. Evidently the distinctive DNA organization at centromeres disfavors cDNA integration. We also found a weak consensus sequence for host DNA at integration sites, and assays of integration in vitro indicated that this sequence is favored as naked DNA, revealing in addition an influence of target primary sequence.


Midazolam Dose Optimization in Critically Ill Pediatric Patients With Acute Respiratory Failure: A Population Pharmacokinetic-Pharmacogenomic Study.
To develop a pharmacokinetic-pharmacogenomic population model of midazolam in critically ill children with primary respiratory failure. Prospective pharmacokinetic-pharmacogenomic observational study. Thirteen PICUs across the United States. Pediatric subjects mechanically ventilated for acute respiratory failure, weight greater than or equal to 7 kg, receiving morphine and/or midazolam continuous infusions. Serial blood sampling for drug quantification and a single blood collection for genomic evaluation. Concentrations of midazolam, the 1' (1`-hydroxymidazolam metabolite) and 4' (4`-hydroxymidazolam metabolite) hydroxyl, and the 1' and 4' glucuronide metabolites were measured. Subjects were genotyped using the Illumina HumanOmniExpress genome-wide single nucleotide polymorphism chip. Nonlinear mixed effects modeling was performed to develop the pharmacokinetic-pharmacogenomic model. Body weight, age, hepatic and renal functions, and the UGT2B7 rs62298861 polymorphism are relevant predictors of midazolam pharmacokinetic variables. The estimated midazolam clearance was 0.61 L/min/70kg. Time to reach 50% complete mature midazolam and 1`-hydroxymidazolam metabolite/4`-hydroxymidazolam metabolite clearances was 1.0 and 0.97 years postmenstrual age. The final model suggested a decrease in midazolam clearance with increase in alanine transaminase and a lower clearance of the glucuronide metabolites with a renal dysfunction. In the pharmacogenomic analysis, rs62298861 and rs28365062 in the UGT2B7 gene were in high linkage disequilibrium. Minor alleles were associated with a higher 1`-hydroxymidazolam metabolite clearance in Caucasians. In the pharmacokinetic-pharmacogenomic model, clearance was expected to increase by 10% in heterozygous and 20% in homozygous for the minor allele with respect to homozygous for the major allele. This work leveraged available knowledge on nonheritable and heritable factors affecting midazolam pharmacokinetic in pediatric subjects with primary respiratory failure requiring mechanical ventilation, providing the basis for a future implementation of an individual-based approach to sedation.


[Two prize medals from the "Société de Pharmacie de Paris"].
The author describes two medals from the "Société de Pharmacie de Paris", proving that the medal engraved by Brenet was also used as an award by the Société at the beginning of the 19th century. It also describes for the first time the use of a medal with the effigy of Lavoisier engraved by Caqué as a thesis award from 1871 to at least 1914.


Physiologic Thymic Involution Underlies Age-Dependent Accumulation of Senescence-Associated CD4+ T Cells.
Immune aging may underlie various aging-related disorders, including diminished resistance to infection, chronic inflammatory disorders, and autoimmunity. PD-1+ and CD153+ CD44high CD4+ T cells with features of cellular senescence, termed senescence-associated T (SA-T) cells, increasingly accumulate with age and may play a role in the immune aging phenotype. In this article, we demonstrate that, compared with young mice, the aged mouse environment is highly permissive for spontaneous proliferation of transferred naive CD4+ T cells, and it drives their transition to PD-1+ and CD153+ CD44high CD4+ T cells after extensive cell divisions. CD4+ T cells with essentially the same features as SA-T cells in aged mice are also generated from naive CD4+ T cells after extensive cell divisions under severe T-lymphopenic conditions by gamma irradiation or in developmental T cell defect, often in association with spontaneous germinal centers, as seen in aged mice. The increase in SA-T cells is significantly enhanced after thymectomy at the young adult stage, along with accelerated T cell homeostatic proliferation, whereas embryonic thymus implantation in the late adult stage markedly restricts the homeostatic proliferation of naive CD4+ T cells in the host and delays the increase in SA-T cells. Our results suggest that reduced T cell output due to physiologic thymic involution underlies the age-dependent accumulation of SA-T cells as a result of increasing homeostatic proliferation of naive CD4+ T cells. SA-T cells may provide a suitable biomarker of immune aging, as well as a potential target for controlling aging-related disorders.


Labour induction with gestational hypertension: A great obstetric challenge.
To observe the fetomaternal morbidity and mortality with induction of labour in pregnant women with gestational hypertension. The subjected study population included was 138 pregnant women with gestational hypertension. These pregnant women were between 34-40 weeks of gestational period in whom labour was induced, while the pregnant women who had labour induction for other reasons were excluded. These women were registered on the predesigned proforma. The data was collected and analyzed on SPSS version 21. Out of the 138 cases, mean age of the women was 25.93±5.037, prim gravid women were 78(56.5%), gestational period in majority of these women 71(51.4%) varied between 35-38 weeks. The common presenting symptoms were oedema 119(86.23%), headache 90(65.21%). Labour induction in majority of the cases 81(58.7%) was carried with prosten pessary. The Caesarean section was needed in 39(28.3%) women in emergency due to maternal and fetal reasons or due to failed induction. Maternal complications were uncontrolled hypertension 23(16.7%), intensive care unit admission 21(15.2%), fits 15(10.9%), post partum haemorrhage 13(9.4%). Fetal complications were birth asphyxia 49(35.5%), neonatal intensive care unit admission 17(12.3%), neonatal death 14(10.1%). The emergency Caesarean section rate was quite high with induction of labour in pregnant women with gestational diabetes. The maternal morbidity as well as fetal morbidity and mortality rate was also high.


Characterization of Neospora caninum iscom antigens using monoclonal antibodies.
Neospora caninum is a cyst-forming coccidian parasite which in cattle can cause abortion and birth of feeble calves. For the serological diagnosis of neosporosis, antibodies directed to the parasite can be demonstrated by ELISA, utilizing N. caninum proteins incorporated into iscoms (immunostimulating complexes) as antigen. Electrophoretic and immunoblotting studies had earlier revealed that N. caninum iscoms contained a restricted number of proteins compared with soluble parasite extracts, but the cellular origin of the incorporated proteins has not yet been determined. In the present study, monoclonal antibodies were raised against N. caninum iscoms. Six of these, named Ncmab-4, 7, 10, 13, 17 and 24, were used to characterize the N. caninum iscom antigen. The nature of the reactive epitopes and their localization within N. caninum tachyzoites were determined by means of immunological methods, including immunoblot, IFAT and immunogold electron microscopy. The apparent molecular weights of the dominant iscom antigens were found to be 18, 30, 32, 41 and 61 kDa. While the 61 kDa antigen was located intracellularly, the others were found on the parasite surface as well as within distinct intracellular compartments.


Plasma microRNA-based signatures to predict 3-year postoperative recurrence risk for stage II and III gastric cancer.
Our aim was to identify plasma microRNA (miRNA)-based signatures to predict 3-year postoperative recurrence risk for patients with stage II and III gastric cancer (GC), so as to provide insights for individualized adjuvant therapy. Plasma miRNA expression was investigated in three phases, involving 407 patients recruited from three centers. ABI miRNA microarray and TaqMan Low Density Array were adopted in the discovery phase to identify potential miRNAs. Quantitative reverse-transcriptase polymerase chain reaction was used to assess the expression of selected miRNAs. Logistic regression models were constructed in the training set (n = 170) and validated in the validation set (n = 169). Receiver operating characteristic analyses, survival analyses and subgroup analyses were further used to assess the accuracy of the models. We identified a 7 miRNA classifier and 7miR + pathological factors index that provided high predictive accuracy of GC recurrence (area under the curve = 0.725 and 0.841 in the training set; and 0.627 and 0.771 in the validation set). High-risk patients defined by the signatures had significantly shorter disease-free survival and overall survival than low-risk patients. The 7 miRNA classifier is an independent prognostic factor, and could add predictive value to traditional prognostic factors. Subgroup analyses revealed the satisfactory performance persisted regardless of stage, and the two models both displayed high accuracy in stage IIA patients. In conclusion, identified microRNA signature may potentially provide some additional benefit for prediction of disease recurrence in patients with stage II and III GC.


ZEB2 Represses the Epithelial Phenotype and Facilitates Metastasis in Ewing Sarcoma.
The vast majority of cancer-related deaths are attributable to metastasis. Effective treatment of metastatic disease will be improved by a better understanding of the molecular mechanisms contributing to this phenomenon. Much of the work in this field has focused on metastasis of carcinomas, tumors of epithelial origin, while metastasis of sarcomas, tumors of mesenchymal origin, remains poorly understood. Experimental evidence from studies in carcinomas, coupled with clinical observations, highlights the importance of both epithelial and mesenchymal characteristics in these cancer cells that make them competent for metastasis. We set out to test if similar cellular plasticity contributes to sarcoma metastasis. We found that the transcription factor, ZEB2, repressed epithelial gene expression in Ewing sarcoma cells, and this, in turn, repressed the epithelial phenotype. When ZEB2 was experimentally reduced in these cells, epithelial characteristics including decreased migratory ability and cytoskeleton rearrangements were observed. Furthermore, ZEB2 reduction in Ewing sarcoma cells resulted in a decreased metastatic potential using a mouse metastasis model. Our data show that Ewing sarcoma cells may have more epithelial plasticity than previously appreciated. This coupled with previous data demonstrating Ewing sarcoma cells also have mesenchymal features primes these cells to successfully metastasize. This is clinically relevant for 2 important reasons. First, this may offer a therapeutic opportunity to induce characteristics of one cell type or the other depending on the stage of the disease. Second, and more broadly, this raises questions about the cell of origin in Ewing sarcoma and may inform future animal models of the disease.


Lithium Metal Anodes with an Adaptive "Solid-Liquid" Interfacial Protective Layer.
Lithium metal is an attractive anode for the next generation of high energy density lithium-ion batteries due to its high specific capacity (3,860 mAh g-1) and lowest overall anode potential. However, the key issue is that the static solid electrolyte interphase cannot match the dynamic volume changes of the Li anode, resulting in side reactions, dendrite growth, and poor electrodeposition behavior, which prevent its practical applications. Here, we show that the "solid-liquid" hybrid behavior of a dynamically cross-linked polymer enables its use as an excellent adaptive interfacial layer for Li metal anodes. The dynamic polymer can reversibly switch between its "liquid" and "solid" properties in response to the rate of lithium growth to provide uniform surface coverage and dendrite suppression, respectively, thereby enabling the stable operation of lithium metal electrodes. We believe that this example of engineering an adaptive Li/electrolyte interface brings about a new and promising way to address the intrinsic problems of lithium metal anodes.


A learning rule for the emergence of stable dynamics and timing in recurrent networks.
Neural dynamics within recurrent cortical networks is an important component of neural processing. However, the learning rules that allow networks composed of hundreds or thousands of recurrently connected neurons to develop stable dynamical states are poorly understood. Here I use a neural network model to examine the emergence of stable dynamical states within recurrent networks. I describe a learning rule that can account both for the development of stable dynamics and guide networks to states that have been observed experimentally, specifically, states that instantiate a sparse code for time. Across trials, each neuron fires during a specific time window; by connecting the neurons to a hypothetical set of output units, it is possible to generate arbitrary spatial-temporal output patterns. Intertrial jitter of the spike time of a given neuron increases as a direct function of the delay at which it fires. These results establish a learning rule by which cortical networks can potentially process temporal information in a self-organizing manner, in the absence of specialized timing mechanisms.


Modulated structure of Lu4AlCu2B9O23 from low-temperature single-crystal X-ray data.
A second-order phase transition with both displacive and disorder mechanisms was discovered in Lu4AlCu2B9O23 using single-crystal X-ray diffraction techniques by cooling down the sample to 110 K. Low-temperature structure modulations are mainly associated with Cu atoms surrounded by O atoms. The fivefold asymmetric environment leads to a special copper position splitting into a pair of general ones so that four O atoms coordinate each of them. Each copper site is 50% occupied at room temperature, but at lower temperature statistical disorder gives occupation and displacive modulations with a wavevector of q = 0.132c*. Tetragonal P\bar 42(1)m symmetry of the non-modulated phase transforms into an orthorhombic (3+1)-dimensional symmetry, P21212(00γ)00s, whereas the \bar 4 axis becomes the twinning axis.


Penetration of negatively charged lipid interfaces by the doubly deprotonated dipicolinate.
The possibility that a negatively charged organic molecule penetrates the lipid interface in a reverse micellar system is examined using UV-vis absorption and NMR spectroscopy. The hypothesis that deprotonated forms of dipicolinic acid, H(2)dipic, such as Hdipic(-) and dipic(2-), can penetrate the lipid interface in a microemulsion is based on our previous finding that the insulin-enhancing anionic [VO(2)dipic](-) complex was found to reside in the hydrophobic layer of the reverse micelle (Crans et al. J. Am. Chem. Soc. 2006, 128, 4437-4445). Penetration of a polar and charged compound, namely Hdipic(-) or dipic(2-), into a hydrophobic environment is perhaps unexpected given the established rules regarding the fundamental properties of compound solubility. As such, this work has broad implications in organic chemistry and other disciplines of science. These studies required a comprehensive investigation of the different dipic species and their association in aqueous solutions at varying pH values. Combining the aqueous studies using absorption and NMR spectroscopy with those in microemulsions defines the differences observed in the heterogeneous environment. Despite the expected repulsion between the surfactant head groups and the dianionic probe molecule, these studies demonstrate that dipic resides deep in the hydrophobic portion of the reverse micellar interface. In summary, these results provide evidence that ionic molecules can reside in nonpolar locations in microheterogeneous environments. This suggests that additional factors such as solvation are important to molecule location. Documented ability to penetrate lipid surfaces of similar charge provides a rationale for why specific drugs with less than optimal hydrophobicity are successful even though they violate Lipinski's rules.


Synthesis of New N1Arylpiperazine Substituted Xanthine Derivatives and Evaluation of their Antioxidant and Cytotoxic Effects.
Cancer is one of the leading causes of morbidity and mortality worldwide, with approximately 14 million new cases in 2012, with most of the clinically used drugs being ineffective. Methylxanthines have raised more interest in research on modifying their structure because of their diverse biological activity. In addition, the piperazine nucleus is one of the most important heterocycles exhibiting remarkable pharmacological activities. The structure of the obtained compounds was characterized and elucidated by IR, 1H and 13C NMR and LCMS spectral analysis. The purity of the substances was proven by corresponding melting points and elemental analysis. The antioxidant activity was evaluated by four common methods - DPPH, ABTS, FRAP and lipid peroxidation assay. The cytotoxic effects of the tested series were evaluated using the standard MTT-dye reduction assay on three tumour cell lines. A series of new xanthine derivatives comprising an arylpiperazine moiety at N1 were synthesized. The cytotoxicity against human T-cell leukemia cell SKW-3, human acute myeloid leukemia HL-60 and human Bcell precursor leukemia cell REH was evaluated. The relationship between the structure and citotoxicity of the compounds was investigated by quantitative structure-activity relationship (QSAR) analysis and the important structural parameters were drawn. The highest antioxidant activity was demonstrated by compound 6c. The highest cytotoxic effect was observed for compound 6f. It was found that cytotoxicity against SKW-3 depends on the electron density distribution in the structures. Branching of the molecular skeleton and introduction of heteroatoms like fluorine and sulfur in the structures also significantly improved the antiproliferative activity of the compounds.