Confirmation of the Department of Transportation criteria for a substituted urine specimen.
The purpose of this study was to determine whether people could naturally produce urine sufficiently dilute to meet the federal criteria for a "substituted" specimen. The United States Department of Transportation Regulations (49 Code of Federal Regulations Part 40) defines a urine specimen as substituted if it has a creatinine concentration of < or = 5 mg/dL and a specific gravity of < or = 1.001 or > or = 1.020. These criteria have been criticized based on the contention that an insufficient number of specimens had been tested from the same urine sample for both creatinine and specific gravity measurements. We reviewed the results of 803,130 random urine specimens measured for creatinine and/or specific gravity in a hospital-based laboratory. In this database, 13,467 urine specimens had both creatinine and specific gravity measurements. None of these 13,467 paired urine specimens met the lower limit of specific gravity (< or = 1.001) and creatinine (< or = 5 mg/dL) criteria for a Department of Transportation substituted specimen. We also examined the medical records of those patients meeting even one of the two criteria; creatinine concentration < or = 5 mg/dL or specific gravity < or = 1.001. These patients were neonatal, moribund, or so severely ill that essentially none could have been among the working population. These data in patients with various pathologic states support our belief that normal individuals do not produce urine dilute enough to meet the lower limit of the specific gravity (< or = 1.001) and creatinine (< or = 5 mg/dL) required for meeting substituted specimen criteria. Eleven patients met the criteria for a substituted specimen, with elevated specific gravity of > or = 1.020 and creatinine concentration of < or = 5 mg/dL; however, these patients were seriously ill or terminally ill.


Rare-earth metal hydroxylamide complexes.
The rare-earth metal hydroxylamide compound Y[N(SiHMe2)2]2[ONBn2][THF] (1) was prepared by the silylamide elimination pathway from the reaction of N,N-dibenzylhydroxylamine, Bn2NOH (Bn = CH2C6H5), with Y[N(SiHMe2)2]3[THF]2 and was characterised by multinuclear NMR spectroscopy and elemental analysis. The compounds [Cp2Y(ONBn2)]2 (2a) [Cp2Sm(ONBn2)]2 (2b) were obtained by the reactions of MCp3 (M = Y, Sm) with Bn2NOH. The trinuclear compound Cp5Y3[ON(Me)CH2CH2(Me)NO]2 (3) was obtained by the reaction of YCp3 and the bishydroxylamine HON(Me)CH2CH2(Me)NOH. 2a, 2b and 3 were characterised by NMR spectroscopy, single-crystal X-ray diffraction and elemental analysis. In all these complexes side-on-coordination of the hydroxylamide units was observed. The compounds are of dynamic nature in solution.


[International nutrition and health].
Malnutrition is the major underlying determinant of global disease and death. Maternal undernutrition and the premature introduction of complementary foods with low energy-nutrient density lead to low birth weight, impaired growth and intellectual development, and high mortality due to infectious diseases. More than 5 million of the 10 million annual child deaths are due to underlying undernutrition. As a result of rural-urban migration and access to refined sugar and fat, overnutrition and chronic diseases are also becoming an increasing problem among the poor.


Weakly supervised learning for pattern classification in serial femtosecond crystallography.
Serial femtosecond crystallography at X-ray free electron laser facilities opens a new era for the determination of crystal structure. However, the data processing of those experiments is facing unprecedented challenge, because the total number of diffraction patterns needed to determinate a high-resolution structure is huge. Machine learning methods are very likely to play important roles in dealing with such a large volume of data. Convolutional neural networks have made a great success in the field of pattern classification, however, training of the networks need very large datasets with labels. This heavy dependence on labeled datasets will seriously restrict the application of networks, because it is very costly to annotate a large number of diffraction patterns. In this article we present our job on the classification of diffraction pattern by weakly supervised algorithms, with the aim of reducing as much as possible the size of the labeled dataset required for training. Our result shows that weakly supervised methods can significantly reduce the need for the number of labeled patterns while achieving comparable accuracy to fully supervised methods.


Promising therapeutic role of miR-27b in tumor.
MicroRNAs are small nonprotein-encoding RNAs ranging from 18 to 25 nucleotides in size and regulate multiple biological pathways via directly targeting a variety of associated genes in cancers. MicroRNA-27b is a highly conserved MicroRNA throughout vertebrates and there are two homologs (hsa-miR-27a and hsa-miR-27b) in humans. MicroRNA-27b is an intragenic microRNA located on chromosome 9q22.1 within the C9orf3 gene, clustering with miR-23b and miR-24-1 in human. As a frequently dysregulated microRNA in human cancers, microRNA-27b could function as a tumor suppressor or an oncogenic microRNA. More and more studies indicate that microRNA-27b is involved in affecting various biological processes, such as angiogenesis, proliferation, metastasis, and drug resistance, and thus may act as a promising therapeutic target in human cancers. In this review, we discuss the role of microRNA-27b in detail and offer novel insights into molecular targeting therapy for cancers.


Yeast surface display of a noncovalent MHC class II heterodimer complexed with antigenic peptide.
Microbial protein display technologies have enabled directed molecular evolution of binding and stability properties in numerous protein systems. In particular, dramatic improvements to antibody binding affinity and kinetics have been accomplished using these tools in recent years. Examples of successful application of display technologies to other immunological proteins have been limited to date. Herein, we describe the expression of human class II major histocompatibility complex allele (MHCII) HLA-DR4 on the surface of Saccharomyces cerevisiae as a noncovalently associated heterodimer. The yeast-displayed MHCII is fully native as assessed by binding of conformationally specific monoclonal antibodies; failure of antibodies specific for empty HLA-DR4 to bind yeast-displayed protein indicates antigenic peptide is bound. This report represents the first example of a noncovalent protein dimer displayed on yeast and of successful display of wild-type MHCII. Results further point to the potential for using yeast surface display for engineering and analyzing the antigen binding properties of MHCII.


The family management of breastfeeding low birth weight infants.
Human milk plays a vital role in the health and development of low birth weight (LBW) infants, yet the initiation and duration rates of breastfeeding in this population are far below those of term infants. Families play an important role in the breastfeeding experience and therefore may contribute to the overall success or lack thereof of the experience. This qualitative study used naturalistic inquiry to describe the family management styles of 13 breastfeeding families of LBW infants. The family management style conceptual framework guided this inquiry, with management styles emerging from the families' definition of the experience and their management behaviors within their unique sociocultural context. These families described facilitating, maintaining, and obstructing family management styles. Through the identification of distinct management styles, interventions may be developed that will assist these families to achieve their breastfeeding goals.


AutoCore: A network-based definition of the core module of human autoimmunity and autoinflammation.
Although research on rare autoimmune and autoinflammatory diseases has enabled definition of nonredundant regulators of homeostasis in human immunity, because of the single gene-single disease nature of many of these diseases, contributing factors were mostly unveiled in sequential and noncoordinated individual studies. We used a network-based approach for integrating a set of 186 inborn errors of immunity with predominant autoimmunity/autoinflammation into a comprehensive map of human immune dysregulation, which we termed "AutoCore." The AutoCore is located centrally within the interactome of all protein-protein interactions, connecting and pinpointing multidisease markers for a range of common, polygenic autoimmune/autoinflammatory diseases. The AutoCore can be subdivided into 19 endotypes that correspond to molecularly and phenotypically cohesive disease subgroups, providing a molecular mechanism-based disease classification and rationale toward systematic targeting for therapeutic purposes. Our study provides a proof of concept for using network-based methods to systematically investigate the molecular relationships between individual rare diseases and address a range of conceptual, diagnostic, and therapeutic challenges.


[A modified MacConkey medium].
We used MacConkey Agar(MCA) medium powder as a basis and added 6-benzoy-2-naphthyl phosphate disodium salt to modify MCA medium. This method was identified by examining several kinds of enteric pathogenic bacteria. Thus it allows us to observe lactose fermentative and phosphatase reaction simultaneously and to recognize Enterobacteriaceae from non-fermentable bacteria on primary culture plates according to the color of colony. This improved method simplifies the recognition procedure and shortens the time so that it is helpful to correctly choosing identification kit.


Squaraine Dyes Derived from Indolenine and Benzo[e]indole as Potential Fluorescent Probes for HSA Detection and Antifungal Agents.
Four squaraine dyes derived from 2,3,3-trimethylindolenine and 1,1,2-trimethyl-1H-benzo[e]indole with different combinations of barbituric groups attach to the central ring, having ester groups and alkyl chains in the nitrogen atoms of heterocyclic rings were synthesized. These dyes were fully characterized, and their photophysical behavior was studied in ethanol and phosphate-buffered solution. Absorption and emission bands between 631 and 712 nm were detected, with the formation of aggregates in aqueous media, which is typical of this class of dyes. Tests carried out with 1,3-diphenylisobenzofuran allowed us to verify the ability of the dyes to produce singlet oxygen. The interaction of synthesized dyes with human serum albumin (HSA) was also evaluated, being demonstrated a linear correlation between fluorescence intensity and protein concentration. The antifungal potential of the dyes against the yeast Saccharomyces cerevisiae was evaluated using a broth microdilution assay. In order to test the photosensitizing capacity of the synthesized dyes, tests were carried out in the dark and with irradiation, using a custom-built light-emitting diode that emits close to the absorption wavelength of the studied dyes. The results showed that the interaction of dyes with HSA and the antifungal activity depends on the different structural modifications of the dyes.


Increased leukocyte adhesiveness/aggregation is the single best biochemical indicator of disease activity in adolescent patients with inflammatory bowel disease.
We determined the relative utility of inflammatory markers in evaluating disease activity in adolescent patients with inflammatory bowel disease (IBD). Sixty-one adolescent patients and 50 age and sex matched volunteers who served as controls were evaluated prospectively. The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), white blood cell count (WBCC), and the leukocyte adhesiveness/aggregation (LAA) test were determined in each patient. There were 28 subjects in remission and 33 in relapse. Their percentage of aggregated white blood cells in the peripheral blood was 7 +/- 5 and 16 +/- 8, respectively, when compared with the control group (5 +/- 3) (p < 0.0001). Moreover, the LAA test was the only one which could effectively classify patients with IBD into their correct diagnostic categories of remission, mild-moderate, or moderate-severe disease activity. The LAA test is superior to other acute phase reactants used in daily practice to detect the presence of inflammation as well as for the assessment of its severity in adolescent patients with IBD. In addition, our findings may have biological relevance to the disease process and its potential manipulation by anti-adhesive agents.


Predictors of long-term event-free survival after percutaneous balloon mitral valvuloplasty.
Previous studies have shown that long-term event-free survival after percutaneous balloon mitral valvuloplasty (PBMV) could be predicted by several baseline characteristics. However, the extent of the predictive variables has not been defined accurately yet. In this study, 40 baseline demographic, clinical, echocardiographic, and hemodynamic variables of 128 consecutive patients with mitral stenosis who underwent PBMV in a single institution, were analyzed in order to predict long-term event-free survival, defined as absence of death, mitral valve replacement, or repeat PBMV. Univariate survival analysis showed that age (p = 0.03), history of commissurotomy or mitral valvuloplasty (p = 0.05), calcium grade (p = 0.008), echo score (p = 0.0001), preprocedure cardiac output (p = 0.03), preprocedure valve area (p = 0.0007), postprocedure mean left atrial pressure (p = 0.0001), postprocedure valve area (p = 0.0001), postprocedure valve gradient (p = 0.013), and postprocedural mitral regurgitation (p = 0.01) were statistically significant predictors of event-free survival. Additionally, the absolute and/or relative procedural change of the following variables were found to be statistically significant predictors of event-free survival: left atrial pressure (p = 0.01), valve area (p = 0.0001), and valve gradient (p = 0.02). Multivariate Cox proportional hazard analysis indicated that when only variables available before the procedure were considered, echo score (p = 0.002) and preprocedure valve area (p = 0.0002) were found to be independent predictors of event-free survival. When both pre- and postprocedure variables were considered, echo score (p = 0.002) and postprocedure valve area (p = 0.0001) were found to be independent predictors of event-free survival. In conclusion, mitral valve morphology reflected by echo score, and baseline and postprocedure mitral valve area were found to be the strongest independent predictors of event-free survival after PBMV.


Expression modes of interferon-alpha inducible genes in sensitive and resistant human melanoma cells stimulated with regular and pegylated interferon-alpha.
Interferon-alpha with its antiproliferative activity is widely used for the treatment of viral infections and tumor therapy such as melanoma. Naturally occurring resistance to recombinant interferon alpha-2a (IFN-alpha) and severe side effects limit the therapeutic efficacy. Understanding of the molecular mechanisms involved in unresponsiveness may therefore lead to the development of novel formulations that overcome resistance. Here, we have applied oligonucleotide DNA microarrays with probe sets for about 11,400 human transcripts to study the expression of interferon-alpha inducible genes in a sensitive and resistant melanoma cell line over multiple time points and two interferon formulations. We identified two major groups of genes with termed interferon primary response genes (IPRGs) or interferon secondary response genes (ISRGs). IPRGs are upregulated early after interferon stimulation in both the sensitive and the resistant line and they contain IREs in the noncoding regulatory region. In contrast, ISRG expression occurs preferentially in the sensitive line ME15 at late time points, and this group of genes lacks typically IREs. In addition to these two major interferon response gene classes, we identified a relatively small number of genes with complex kinetic expression modes. In addition, we show for the first time that regular and pegylated recombinant interferons are equally potent activators of interferon (IFN) gene expression. Finally, we propose that the ISRGs are activated downstream of the primary response genes by a molecule or pathway, which awaits identification, and interferon inducible gene expression is thus more complicated than previously thought.


What effect did the New Zealand COVID-19 lockdown have on computed tomography-head scan utilisation in patients presenting to the emergency department with traumatic head injuries?
To explore the unique impact the first COVID-19 national lockdown in New Zealand (NZ) had on the utility of computed tomography (CT)-head scanning in patients presenting to the ED with head injuries. Retrospective observational study of CT-head use in head-injured patients presenting to the ED during the 2020 COVID-19 lockdown compared to the corresponding time period in 2019. During the lockdown period in 2020, the total number of ED presentations reduced by 30.3% (95% confidence interval [CI] 28.8-31.6) from 13 477 to 9403. The total number of head injury presentations also reduced by 32% (95% CI 27-36.7) from 523 to 356. The proportion of head-injured patients remained similar (3.9% [n = 523] in 2019 vs 3.8% [n = 356] in 2020). Of the head injured patients, 185 (51.9%, 95% CI 44.5-59.4) had CT-head scans performed in 2020 compared to 269 (51.4%, 95% CI 45.2-57.5) in 2019; a reduction of 31.2% (95% CI 24.5-37.9). The proportion of patients who had a CT-head scan remained similar (51.4% [95% CI 45.2-57.5] in 2019 vs 51.9% [95% CI 44.5-59.4] in 2020). There were no significant differences in the proportion of CT-head scans with acute traumatic pathology (13.0% [95% CI 8.7-17.3] in 2019 vs 12.4% [95% CI 7.4-17.5] in 2020, P = 0.86). During the first COVID-19 lockdown in NZ, the total number of patients presenting to the ED decreased by one third. Reassuringly, the proportion of patients who presented with head injuries, had a CT-head scan performed, and had positive CT-head findings remained the same as the previous year.


Determination of Antidepressants and Antipsychotics in Dried Blood Spots (DBSs) Collected from Post-Mortem Samples and Evaluation of the Stability over a Three-Month Period.
An LC-MS/MS method for the identification and quantification of antidepressants and antipsychotics was developed on dried blood spots (DBSs). Moreover, analyte stability on DBSs within a 3-month period was monitored. Aliquots of 85 µL of blood from autopsy cases were pipetted onto DBS cards, which were dried and stored at room temperature. DBSs were analyzed in triplicate immediately, within the following 3 weeks, and after 3 months. For each analysis, a whole blood stain was extracted in phosphate buffer and purified using Solid Phase Extraction (SPE) cartridges in order to avoid matrix effects and injected in the LC-MS/MS system. Thirty-nine molecules were screened. Limits of detection (LODs) ranged between 0.1 and 3.2 ng/mL (g) and 0.1 and 5.2 ng/mL (g) for antidepressants and antipsychotics, respectively. Limits of quantification (LOQs) varied from 5 to 10.0 ng/mL for both. Sixteen cases among the 60 analyzed resulted positive for 17 different analytes; for 14 of these the method was fully validated. A general good agreement between the concentrations on DBSs and those measured in conventional blood samples (collected concurrently and stored at -20 °C) was observed. The degradation/enhancement percentage for most of the substances was lower than 20% within the 3-month period. Our results, obtained from real post-mortem cases, suggest that DBSs can be used for routine sample storage.


Maize pollen diet enhances malaria mosquito longevity and infectivity to Plasmodium parasites in Ethiopia.
Although larval diet quality may affect adult mosquito fitness, its impact on parasite development is scarce. Plant pollen from Zea mays, Typha latifolia, and Prosopis juliflora was ultraviolet-sterilized and examined for effects on larval development, pupation rate, adult mosquito longevity, survival and infectivity. The control larvae were fed Tetramin fish food as a comparator food. Four treatment and two control groups were used for each pollen diet, and each experimental tray had 25 larvae. Female An. arabiensis were starved overnight and exposed to infectious blood using a membrane-feeding system. The Kaplan-Meier curves and log-rank test were used for analysis. The Z. mays pollen diet increased malaria mosquito survival and pupation rate (91.3%) and adult emergence (85%). Zea mays and Tetramin fish food had comparable adulthood development times. Adults who emerged from larvae fed Z. mays pollen had the longest average wing length (3.72 mm) and were more permissive to P. vivax (45%) and P. falciparum (27.5%). They also survived longer after feeding on infectious blood and had the highest number of P. vivax oocysts. Zea mays pollen improved larval development, adult mosquito longevity, survival and infectivity to Plasmodium. Our findings suggest that malaria transmission in Z. mays growing villages should be monitored.


Two-step melting of the vortex solid in layered superconductors with random columnar pins.
We consider the melting of the vortex solid in highly anisotropic layered superconductors with a small concentration of random columnar pinning centers. Using large-scale numerical minimization of a free-energy functional, we find that melting of the low-temperature, nearly crystalline vortex solid (Bragg glass) into a vortex liquid occurs in two steps as the temperature increases: the Bragg glass and liquid phases are separated by an intermediate Bose glass phase. A suitably defined local melting temperature exhibits spatial variation similar to that observed in experiments.


Purification and characterization of animal porphobilinogen synthases. I. Bovine liver porphobilinogen synthase.
Porphobilinogen synthase was purified from ox liver by ammonium sulfate fractionation, heat denaturation and column chromatography (purification: 400-fold; specific activity 4.72 nkat). The molecular weight of the native enzyme obtained by thin-layer gel filtration is about 280 000. Using 8M urea in the presence of dithiothreitol as reducing agent, the molecule breaks down into 8 subunits of molecular weight 36 000 (dodecylsulfate gel electrophoresis); the preparation of aminoethylated subunit is described. According to the above-mentioned molecular weight and to the above-mentioned molecular weight and to the quantitative amino acid analysis after total hydrolysis, the following compositon of the enzymes subunit was calculated ASX23-25 Thr7 Ser23-24 Glx29-31 Pro22-23 Gly22-24 Ala36-37 Val23-26 Met7 Ile9 Leu34-35 Tyr10 Phe11-12 Lys11-12 Cys6-7 His6-8 Arg22 Trp1-2. The subunits, having two free sulfhydryl groups, therefore consists of a chain of about 306 amino acids. The Dansyl-Edman procedure did not enable identification of any free N-terminal amino acid. The acyl group blocking the N-terminus is an acetyl group. It was identified, after hydrazinolysis of the enzyme, by means of chromatographic comparison with 1-formyl-2-dansyl-hydrazine and 1-acetyl-2-dansylhydrazine, whose syntheses and UV spectra are described.


The improved quality of postoperative analgesia after intrathecal morphine does not result in improved recovery and quality of life in the first 6 months after orthopedic surgery: a randomized controlled pilot study.
In orthopedic surgery, it is well known that the use of intrathecal morphine (ITM) leads to an improved quality of postoperative analgesia. Little is known how this improved analgesia affects the long-term course after surgery. A randomized, double-blind trial. Academic medical center. Forty-nine patients undergoing total hip or knee replacement surgery in spinal anesthesia. Patients were randomly assigned to receive either 0.1 mg (n=16) or 0.2 mg (n=16) morphine sulfate intrathecally or physiological saline (n=17) added to 3 mL 0.5% isobaric bupivacaine for spinal anesthesia. As a function of the quality of the short-term postoperative analgesia, the effect on recovery and quality of life was evaluated at various time points up to 26 weeks after surgery. In both ITM groups, the additionally required postoperative systemic morphine dose was significantly reduced compared with the placebo group (P=0.004). One week after operation, patients with ITM reported significantly less pain at rest (P=0.01) compared to the placebo group. At discharge, in comparison with the 0.1 mg ITM and placebo group, the 0.2 mg ITM group showed a higher degree of impairment regarding pain, stiffness, and physical function of the respective joint (P=0.02). Over the further follow-up period of 6 months after surgery, recovery and the quality of life did not differ significantly between the three study groups (P>0.2). Morphine (0.1 mg) as adjunct to 0.5% bupivacaine for spinal anesthesia is effective to produce a pronounced postoperative analgesia with a beneficial analgesic effect up to 1 week after surgery. With this study design, the different quality of postoperative analgesia had no effect on quality of life and recovery in patients over the 6-month follow-up period. In the medium term, ITM may induce hyperalgesic effects.


Impact of minimum unit pricing on youth alcohol consumption: insights from Lebanon.
This paper analyses the impact of introducing an alcohol minimum unit pricing policy on youth's off-premise alcohol consumption. We rely on price elasticities derived using stated preference alcohol purchase data from a survey of 1024 university students in Lebanon. Selectively targeting drinks with high ethanol concentration by applying a minimum unit pricing (MUP) corresponding to the maximum price that respondents are willing to pay per beverage achieves a reduction in ethanol intake close to 0.23 l/month (∼28% of pre-MUP ethanol intake). Imposing a flat MUP corresponding to the average price respondents are willing to pay for all alcoholic beverages decreases ethanol intake by nearly half the reduction from the previous targeted MUP. This work provides evidence in favour of MUP in conjunction with taxation capable of substantially reducing alcohol consumption. We also document a positive welfare benefit of MUP.


A highly selective colorimetric and fluorescent dual-modal probe for the rapid determination of fluoride anions.
In this work, 4-(p-hydroxybenzylidenehydrazino)-N-butyl-1,8-naphthalimide (1) has been designed and synthesized as a colorimetric and fluorescent dual-modal probe for F- . Compound 1 immediately detected inorganic fluoride salts using UV/vis absorption and fluorescence spectroscopy methods, and served as a 'naked-eye' indicator for F- with high selectivity and sensitivity. Both the absorption and fluorescence spectra show excellent linearity with the concentration of F- . Real-life applications demonstrated that our proposed analytical system provided a satisfactory method for the determination of F- . In addition, the reaction mechanism of deprotonation was confirmed by 1 H NMR.


Red grape seed extract and its compound resveratrol exert cytotoxic effect to various human cancer lines.
Modern medicinal agents currently available for treatment of cancers are very expensive, toxic, and less effective in treating some of the disease. Thus, one must investigate further in detail the agents derived from natural sources, such as grape seed, for the prevention and treatment of cancer and disease. In recent years interest of researchers has focused on grape seed and nowadays scientists have used extracts of grape seed to treat different health problems including cancer. We examined the cytotoxic effect of red grape seed extract (GSE) and its main compound resveratrol (RES) on different human cancer cell lines representing various solid tumors and hematological malignancies at the same time. Red GSE was prepared by using 1, 1, 1, 2- Tetrafluoroethane extraction method. Cytotoxicity of the extract and RES was evaluated by using trypan blue dye exclusion method and MTT assay. The results of our study show that GSE and RES have cytotoxic activities in varying degree in several cancer cell lines. There has not been any study evaluating the GES and RES in the same cell lines and in the same conditions. But, it is still needed to have more pre-clinical and laboratory studies to validate the usefulness of these agents either alone or in combination with existing therapy.


Calibration of kVp meters used in quality control tests in diagnostic radiology by spectrometry.
A non-invasive calibration methodology of quality control instruments for diagnostic radiology was established and applied to different kinds of commercial kVp meters. The method uses the measurement of the spectrum endpoint as a reference. The results showed a variation of 10% between the responses of the instruments calibrated and the spectrometric system, a fact that demonstrates the need for instrument calibration.


Exploring Dynamics of Water, Energy, and Food Systems in Agricultural Landscapes Using Mental Modeling: A Case of Varamin Plain, Iran.
This study applies the mental model and cognitive mapping method to involve stakeholders in delineating the mutual relations between sources of water, energy, and food (WEF) production in the Varamin Plain (VP). Through involving farmers and managerial experts, the approach facilitates the deployment of community communication patterns to recognize and comprehend problems and move from single-loop learning to double-loop learning. The dynamic model was driven from the final mental model of the participants to reflect changes in the systems over time. The system dynamic (SD) model incorporates three scenarios for enhancing irrigation efficiency, managing groundwater extraction, and satisfying environmental needs. The results uncovered that the surface and underground water resources of the VP will gradually decrease within the next two decades in the range of 158 and 2700 million cubic meters (MCM) per year. Also, the plain suffers from water insecurity and a 162 MCM shortage. Consequently, focusing on understanding the nexus and nexus governance can enhance resource management and achieve sustainable development goals. Essentially, promoting collaborative governance, such as creating cooperative organizations and implementing double-loop learning, and instituting a water market, regulatory governance, and monitoring laws can improve the state of Varamin Plain's resources. These results carry important policy implications for using mental models to consider dynamics for discussions on participatory management of the WEF system nexus and environmental management.


Laser acupuncture and intravascular laser irradiation of blood for management of pediatric dental anxiety.
The aim of this study was to assess the effectiveness of laser acupuncture and intravascular laser irradiation of blood (ILIB) for managing anxiety in pediatric dentistry. Eighty-four children recruited at a university dental clinic were randomly assigned to three groups: the Sham group (n = 27) underwent sham laser irradiation of three acupuncture points, the ILIB group (n = 25) underwent 10 min of ILIB, and the laser acupuncture group (LAC, n = 32) underwent 40 s of laser acupuncture over points VG20 (Baihui), PC6 (Neiguan), and the Oppression Point. The results suggest that ILIB and laser acupuncture are feasible alternatives for managing dental anxiety in children.


Histologic comparison of healing after tooth extraction with ridge preservation using mineralized versus demineralized freeze-dried bone allograft.
Allografts, such as demineralized freeze-dried bone allograft (DFDBA) and mineralized freeze-dried bone allograft (FDBA) are commonly used by clinicians for ridge preservation procedures. The primary objective of this study is to histologically evaluate and compare the healing of non-molar extraction sockets grafted with DFDBA versus FDBA for ridge preservation. The secondary aim of this study is to compare dimensional changes in ridge height and width after grafting with these two materials. Forty patients were randomly divided into two groups of 20. Extraction sockets were filled with either FDBA or DFDBA. To minimize variables associated with the organ donor and with tissue processing, all of the graft material was procured from a single donor; the only difference in the two materials was the percentage mineralization of the final bone graft. A 2-mm-diameter core biopsy was taken from each grafted site ≈19 weeks after grafting. Histomorphometric analysis was performed to determine percentage of vital bone, residual graft particles, and connective tissue (CT)/other non-bone components. There were no significant differences when comparing changes in alveolar ridge dimensions of the two groups. There was no significant difference in percentage CT/other between groups. DFDBA had a significantly greater percentage of vital bone at 38.42% versus FDBA at 24.63%. The DFDBA group also had a significantly lower mean percentage of residual graft particles at 8.88% compared to FDBA at 25.42%. This study provides the first histologic and clinical evidence directly comparing ridge preservation with DFDBA versus FDBA in humans and demonstrates significantly greater new bone formation with DFDBA.


Alternative system for detection and mapping of activation domains.
The ZEBRA protein is a transcriptional activator that induces expression of viral lytic genes in cells harboring latent Epstein-Barr virus (EBV). In this report it is shown that a derivative of ZEBRA that cannot activate transcription (Zd) can be used to detect and characterize activation domains. Three expression vectors that allow the fusion of putative activation regions in any reading frame were constructed using Zd. These vectors were used to demonstrate the activity of different classes of activation domains using a chloramphenicol acetyltransferase (cat) reporter gene construct containing seven ZEBRA response elements (Z7). The Zd/Z7 system effectively detected proline-rich, glutamine-rich and acidic activation domains in a variety of cell lines and cell types. Using a bioassay unique to the EBV Zd/Z7 system, fusion constructs can also be tested for the ability to activate gene expression directly from a chromatin structure, the EBV genome. These studies indicate that the Zd/Z7 system is an alternative to GAL4 and can be a useful tool for identifying heterologous activation domains.


The AP-1 Complex is Required for Proper Mucilage Formation in Arabidopsis Seeds.
The adaptor protein (AP) complexes play crucial roles in vesicle formation in post-Golgi trafficking. Land plants have five types of AP complexes (AP-1 to AP-5), each of which consists of two large subunits, one medium subunit and one small subunit. Here, we show that the Arabidopsis AP-1 complex mediates the polarized secretion and accumulation of a pectic polysaccharide called mucilage in seed coat cells. Previously, a loss-of-function mutant of AP1M2, the medium subunit of AP-1, has been shown to display deleterious growth defects because of defective cytokinesis. To investigate the function of AP-1 in interphase, we generated transgenic Arabidopsis plants expressing AP1M2-GFP (green fluorescent protein) under the control of the cytokinesis-specific KNOLLE (KN) promoter in the ap1m2 background. These transgenic plants, designated pKN lines, successfully rescued the cytokinesis defect and dwarf phenotype of ap1m2. pKN lines showed reduced mucilage extrusion from the seed coat. Furthermore, abnormal accumulation of mucilage was found in the vacuoles of the outermost integument cells of pKN lines. During seed development, the accumulation of AP1M2-GFP was greatly reduced in the integument cells of pKN lines. These results suggest that trans-Golgi network (TGN)-localized AP-1 is involved in the trafficking of mucilage components to the outer surface of seed coat cells. Our study highlights an evolutionarily conserved function of AP-1 in polarized sorting in eukaryotic cells.


18F-fluorodeoxyglucose-positron emission tomography is more sensitive than computed tomography in initial staging of patients with an anaplastic T-cell lymphoma first presenting in the skin.
The role of 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) in the evaluation of anaplastic large-cell lymphoma (ALCL) first presenting in the skin is not well established, while computed tomography (CT) is used as a standard procedure. The aim of this study was to evaluate the use of FDG-PET versus CT at initial staging of ALCL first presenting in the skin. Eleven cases of ALCL first presenting in the skin who underwent both FDG-PET and CT were retrospectively analysed. There were six males and five females, with a mean age of 59.7 years. Results of FDG-PET were compared with those of CT. Biopsy results of lesions served as a reference for the accuracy of PET and CT in the evaluation of local and metastatic lesions. In seven cases (64%), imaging revealed extracutaneous ALCL. FDG-PET results were concordant with CT results in five cases (45%); in four of these cases, FDG-PET was negative, consistent with CT, and one case had cutaneous and extracutaneous lesions detectable on both CT and FDG-PET. FDG-PET and CT were discordant in six cases (55%). Among these six cases, FDG-PET revealed extracutaneous lesions undetected on CT which consequently influenced the therapeutic decision in five cases (45%). The sensitivity of CT and FDG-PET was 18% and 64%, respectively.


Transport coefficients of helium-argon mixture based on ab initio potential.
The viscosity, thermal conductivity, diffusion coefficient, and thermal diffusion factor of helium-argon mixtures are calculated for a wide range of temperature and for various mole fractions up to the 12th order of the Sonine polynomial expansion with an ab initio intermolecular potential. The calculated values for these transport coefficients are compared with other data available in the open literature. The comparison shows that the obtained transport coefficients of helium-argon mixture have the best accuracy for the moment.


Biphasic action of forskolin on growth hormone and prolactin secretion by rat anterior pituitary cells in vitro.
To assess the role of cAMP-mediated signal transduction processes in mediation of secretagogue-stimulated GH release, we examined the dose-related effects of the diterpene adenylate cyclase activator forskolin (FSK) in primary monolayer cultures of rat adenohypophyseal cells. In cell cultures prepared from both immature (12 days old) and adult (6 weeks to 4 months old) male or female rats, the dose-related stimulation of GH release by FSK was biphasic. With increasing FSK concentrations from 0.03-3.16 microM, GH release increased progressively to maximal values of 442 +/- 19% and 303 +/- 10% of basal release in cells from immature and adult rats, respectively. FSK concentrations above 3.16 microM induced progressively diminished GH responses, with net inhibition to below basal release evident at 100 microM FSK. FSK stimulated PRL release to a lesser degree than it did GH release; the PRL response to FSK was also biphasic. When maximal stimulatory concentrations (Emax) of FSK and GH-releasing factor (GRF; 10 nM) were added in combination, the GH response was significantly less than the individual response to either secretagogue alone. In response to FSK alone, GRF alone, and FSK plus GRF, GH release was 478 +/- 7%, 583 +/- 11%, and 244 +/- 5%; 278 +/- 4%, 283 +/- 3%, and 175 +/- 2%; and 299 +/- 12%, 351 +/- 5%, and 191 +/- 17% of basal release in cells from 12-day-old, adult male, and adult female rats, respectively (P less than 0.01 for all responses to combined addition vs. the individual responses). Submaximal stimulatory concentrations of GRF added in combination with submaximal FSK elicited partially additive GH responses; the GH response to Emax GRF, on the other hand, was inhibited in a dose-related manner by all concentrations of FSK that by themselves were stimulatory. The GH responses were also suppressed when Emax FSK was added to cultured cells of 12-day-old rats in combination with Emax cholera toxin (2.5 ng/ml) or prostaglandin E2 (10 microM), agents whose actions, like that of GRF, involve adenylate cyclase activation. In contrast, FSK did not suppress but in most cases augmented the maximal GH responses to secretagogues whose action is independent of adenylate cyclase activation: (Bu)2cAMP (0.5 mM), TRH (100 nM), phorbol myristate acetate (50 nM), the Ca2+ ionophore A23187 (250 microM), and the dihydropyridine Ca2+ channel agonist BAY K8644 (10 microM). Indeed, combined addition of FSK with the latter two agents resulted in synergistic stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)


Hypopharyngeal presentation of cicatricial pemphigoid: videofluorographic and direct laryngoscopic findings.
Cicatricial pemphigoid can affect all mucosa of the upper aerodigestive tract; however, hypopharyngeal involvement is less frequent. This paper presents a 69-year-old male diagnosed as having cicatricial pemphigoid who was experiencing difficulty swallowing. Videofluorography with barium swallow demonstrated narrow flow through the medial hypopharynx, but not through the lateral hypopharynx. Direct laryngoscopy revealed that the postcricoid hypopharyngeal lumen had become narrow due to circumferential scar formation. Interestingly, detached thin membranous webs were observed beyond the circumferential scar. This report describes important videofluorographic and direct laryngoscopic findings showing rare hypopharyngeal involvement in a case of cicatricial pemphigoid.


Evolution and maintenance of the environmental component of the phenotypic variance: benefit of plastic traits under changing environments.
How environmental variances in quantitative traits are influenced by variable environments is an important problem in evolutionary biology. In this study, the evolution and maintenance of phenotypic variance in a plastic trait under stabilizing selection are investigated. The mapping from genotypic value to phenotypic value of the quantitative trait is approximated by a linear reaction norm, with genotypic effects on its phenotypic mean and sensitivity to environment. The environmental deviation is assumed to be decomposed into environmental quality, which interacts with genotypic value, and residual developmental noise, which is independent of genotype. Environmental quality and the optimal phenotype of stabilizing selection are allowed to randomly fluctuate in both space and time, and individuals migrate equally before development and reproduction among different niches. Analyses show that phenotypic plasticity is adaptive within variable environments if correlations have become established between the optimal phenotype and environmental quality in space and/or time. The evolved plasticity increases with variances in optimal phenotypes and correlations between optimal phenotype and environmental quality; this further induces increases in mean fitness and the environmental variance in the trait. Under certain circumstances, however, the environmental variance may decrease with increase in variation in environmental quality.


Body mass index, gender, and ethnic variations alter the clinical implications of the epworth sleepiness scale in patients with suspected obstructive sleep apnea.
The Epworth Sleepiness Scale (ESS) is often used in the evaluation of obstructive sleep apnea (OSA), though questions remain about the influence gender, ethnicity, and body morphometry have in the responses to this questionnaire. The aim of this study was to examine differences in ESS scores between various demographic groups of patients referred for polysomnography, and the relationship of these score to sleep-disordered breathing Nineteen hundred consecutive patients referred for polysomnographic diagnosis of OSA completed questionnaires, including demographic data and ESS. OSA was determined based on a respiratory disturbance index (RDI) ≥15 by polysomnography. In this high risk population for OSA, the ESS was 10.7 ± 5.6. The highest ESS scores were seen in obese males; non-obese females and non-obese Caucasian males scored the lowest. ESS was weakly correlated with RDI (r = 0.17, P < 0.0001). The sensitivity of ESS for the diagnosis of OSA was 54% and the specificity was 57%. The positive (PPV) and negative (NPV) predictive values were 64% and 47%, respectively. In obese subjects, the sensitivity and specificity were 55% and 53%, compared with 47% and 63% in non-obese subjects. In obese, Hispanic males, the sensitivity, specificity, and PPV were 59%, 54%, and 84%, respectively. In non-obese, Caucasian females, the sensitivity, specificity, and NPV were 43%, 59%, and 72%. The ESS appears to be affected by many factors, including gender, ethnicity, and body morphometry. The ability of the ESS to predict OSA is modest, despite a significant correlation with the severity of OSA. The test characteristics improve significantly when applied to select populations, especially those at risk for OSA.


Screening instruments for substance use and brief interventions targeting adolescents in primary care: a literature review.
A review of the literature was conducted to examine substance use screening instruments commonly used with adolescents in medical settings, their comparative usefulness, and SBIRT (Screening, Brief Intervention, and Referral to Treatment). We screened two databases (Ovid MEDLINE and PsycINFO) targeting journal articles dealing with screening for alcohol and drug use in adolescence as well as adolescent SBIRT. Adolescents preferred paper forms and computerized questionnaires over interviews with physicians or nurses. The CRAFFT was the best studied instrument for screening for alcohol/drug use and related problems, and is the only tool with data to support its use in medical settings. Other screening instruments require more testing/evaluation in more representative samples of adolescents in primary care settings. Long term follow-up data to establish the efficacy of SBIRT in adolescence are not available. Innovative computerized approaches to screening for substance use in this population have recently been proposed. Although promising, they require further evaluation. The CRAFFT has the most consistent data to support its use in primary care settings. The effects of SBIRT in adolescence have not been adequately evaluated. Adolescents' opinions and preferences for SBIRT should be studied to improve their acceptance.


Prostate-Specific Membrane Antigen-Targeted Imaging With [18F]DCFPyL in High-Grade Gliomas.
High-grade gliomas (World Health Organization grade III-IV) are highly lethal primary brain tumors. Imaging modalities, including MRI and FDG PET, provide a limited ability to differentiate treatment effects (such as radiation necrosis) from recurrent or residual tumor. As the first step in validating the applicability of prostate-specific membrane antigen (PSMA)-targeted imaging in high-grade gliomas, we evaluated the ability of the PSMA-targeted small molecule [F]DCFPyL (2-(3-(1carboxy-5-(6-[F]fluoro-pyridine-3-carbonyl)-amino]-pentyl)-ureido)-pentanedioic acid) to image high-grade gliomas in a series of 3 prospectively recruited patients. We found [F]DCFPyL binds PSMA in the neovasculature of glioblastoma multiforme and tumor cells of anaplastic astrocytoma.


Nitrogen doped TiO2-Cu(x)O core-shell mesoporous spherical hybrids for high-performance dye-sensitized solar cells.
We report on high-performance dye-sensitized solar cells (DSSCs) based on nitrogen doped anatase TiO2-CuxO core-shell mesoporous hybrids synthesized through a facile and controlled combined sol-gel and hydrothermal process in the presence of hexadecylamine as the structure-directing agent. The matching of band edges between CuxO and TiO2 to form a semiconductor heterojunction plays an important role in effective separation of light induced electrons and holes, providing a promising photoanode for DSSCs because of its wide absorption spectrum, high electron injection efficiency, and fast electron transference. DSSCs based on the mesoporous TiO2-CuxO core-shell hybrids show a high short-circuit current density of 9.60 mA cm(-2) and a conversion efficiency of 3.86% under one sun illumination. While DSSCs based on the N-doped mesoporous TiO2-CuxO hybrids exhibit the higher short-circuit current density of 13.24 mA cm(-2) and a conversion efficiency of 4.57% under one sun illumination. In comparison with un-doped TiO2-CuxO hybrids, the doping of nitrogen into the lattice of TiO2 can extend the light absorption in the ultraviolet range to the visible light region and effectively decrease the recombination rate of photo-generated electrons and holes. The presented N-doped mesoporous TiO2-CuxO hybrids as photoanodes could find potential applications for high performance DSSCs.


Syntheses of 5'-substituted analogues of carbocyclic 3-deazaadenosine as potential antivirals.
Various 5'-substituted derivatives (2, 3, 6a, 6b, 9a, 9b, 12, 13b, and 15) of carbocyclic 3-deazaadenosine (3-deaza CAdo, 1) were prepared from 3-deaza CAdo (1) and evaluated as antiviral agents against a number of viruses, including HIV-1. Several of the compounds had moderate to good antiviral activity against vaccinia (VV) and vesicular stomatitis (VSV) viruses; however, the antiviral activity of the analogues did not exceed that of the parent compound. No anti-HIV activity was detected.


Ovarian Cancer Risk in Relation to Blood Cholesterol and Triglycerides.
The association between circulating cholesterol and triglyceride levels and ovarian cancer risk remains unclear. We prospectively evaluated the association between cholesterol [total, low-density lipoprotein (LDL-C), and high-density lipoprotein (HDL-C)] and triglycerides and ovarian cancer incidence in a case-control study nested in the Nurses' Health Study (NHS) and NHSII cohorts and a longitudinal analysis in the UK Biobank. A total of 290 epithelial ovarian cancer cases in the NHS/NHSII and 551 cases in UK Biobank were diagnosed after blood collection. We observed a reduced ovarian cancer risk comparing the top to bottom quartile of total cholesterol [meta-analysis relative risk (95% confidence interval): 0.81 (0.65-1.01), P trend 0.06], with no heterogeneity across studies (P heterogeneity = 0.74). Overall, no clear patterns were observed for HDL-C, LDL-C, or triglycerides and ovarian cancer risk. Comparing triglyceride levels at clinically relevant cut-off points (>200 vs. ≤200 mg/dL) for cases diagnosed more than 2 years after blood draw saw a positive relationship with risk [1.57 (1.03-2.42); P heterogeneity = 0.003]. Results were similar by serous/non-serous histotype, menopausal status/hormone use, and body mass index. Data from two large cohorts in the United States and United Kingdom suggest that total cholesterol levels may be inversely associated with ovarian cancer risk, while triglycerides may be positively associated with risk when assessed at least 2 years before diagnosis, albeit both associations were modest. This analysis of two large prospective studies suggests that circulating lipid levels are not strongly associated with ovarian cancer risk. The positive triglyceride-ovarian cancer association warrants further evaluation.


Anterior Pelvic Ring: Introduction to Evaluation and Management.
The evaluation and management of pelvic ring injuries continues to evolve. Historic treatment was primarily nonsurgical, which yielded to open surgical treatment as the benefits of restoring pelvic anatomy and stability became clear. The development of percutaneous techniques for pelvic ring fixation enabled surgeons to reduce and stabilize certain injuries without the need for large open surgical dissections. Although percutaneous iliosacral screw fixation of sacral fractures and sacroiliac disruptions is the standard for most posterior pelvic ring injuries, the evaluation and treatment of anterior pelvic ring disruptions remains a controversial topic among surgeons who treat these injuries. Universally accepted indications for anterior pelvic ring stabilization do not exist, and there is little comparative data to support one surgical technique over another. In fact, some believe that for many injuries, the anterior ring rarely requires fixation after stable fixation of the posterior pelvic ring. The purpose of this work is to present a brief history on management of the anterior pelvic ring as a component of pelvic ring disruptions and briefly review the anatomy of the anterior pelvic ring. Finally, we will introduce the current techniques available for anterior pelvic reduction/stabilization and present information on evaluation of anterior ring stability as a means of guiding treatment.


Platelet-Rich Plasma-Derived Exosomal USP15 Promotes Cutaneous Wound Healing via Deubiquitinating EIF4A1.
Epithelial regeneration is an essential wound healing process, and recent work suggests that different types of exosomes (Exos) can improve wound repair outcomes by promoting such epithelial regeneration. Platelet-rich plasma (PRP) is known to facilitate enhanced wound healing, yet the mechanisms underlying its activity are poorly understood. To explore these mechanisms, we first isolated PRP-derived Exos (PRP-Exos). Using immortalized keratinocytes (HaCaT cells) treated with PBS, PRP, or PRP-Exos, we conducted a series of in vitro Cell Counting Kit-8 (CCK-8), EdU, scratch wound, and transwell assays. We then established a wound defect model in vivo in mice and assessed differences in the mRNA expression within these wounds to better understand the basis for PRP-mediated wound healing. The functions of PRP-Exos and USP15 in the context of wound healing were then confirmed through additional in vitro and in vivo experiments. We found that PRP-Exos effectively promoted the in vitro proliferation, migration, and wound healing activity of HaCaT cells. USP15 was further identified as a key mediator through which these PRP-Exos were able to promote tissue repair both in vitro and in vivo. At a mechanistic level, USP15 enhanced the functional properties of HaCaT cells by promoting EIF4A1 deubiquitination. Thus, PRP-Exos and USP15 represent promising tools that can promote wound healing via enhancing epithelial regeneration.


Pretraining enhances mnemonic training in elderly adults.
One hundred twenty-eight elderly adults were recruited to assess the effects of affective judgment, imagery, and relaxation pretraining on mnemonic training. Participants were assigned to one of the following conditions: (1) visual imagery and affective judgment pretraining plus mnemonic training, (2) visual imagery pretraining only plus mnemonic training, (3) relaxation pretraining plus mnemonic training, (4) nonspecific pretraining plus mnemonic training, (5) nonspecific pretraining only, and (6) wait list. Subjects were tested at three times: prior to training (Time 1), following pretraining (Time 2), and at the conclusion of mnemonic training (Time 3). Although those receiving active pretraining plus mnemonics did not differ from one another at Time 3, they recalled more than those with no active pretraining. The results suggest that for mnemonics to be effective they should be coupled with active pretraining techniques.


Pathways of fear and anxiety in dentistry: A review.
The aim of this article was to analyze the theories underpinning dental fear, anxiety and phobias. To be included, articles must have been published between the years of 1949 and 2013 concerning fears and phobias within dentistry and/or psychiatry. Of 200 articles originally under review, 140 were included and reviewed by the authors.Five specific pathways relating to dental fear and anxiety were identified; Cognitive Conditioning, Informative, Visual Vicarious, Verbal Threat, and Parental. Eight currently accepted management techniques across all dental disciplines for dental fear and anxiety were identified. Further research is required to identify clinical diagnosis and treatment for fears originating from different pathways.


Larval pupation site preference in a few species of Drosophila.
Larval pupation site preference (PSP) is an important event in preadult development. The PSP was studied on the basis of the number of larvae pupated at different sites in the cultures. The results revealed that the larval PSP in different species of Drosophila varies significantly at different sites. The sympatric species also differ in their PSP and the pupation behaviour does not correspond with the taxonomic relationship between the species.


Serial diffusion-weighted magnetic resonance imaging in cases of glioma: distinguishing tumor recurrence from postresection injury.
Diffusion-weighted magnetic resonance (MR) imaging is an invaluable tool in the diagnosis of acute stroke and other types of brain injury. Abnormalities in and around the resection cavity on diffusion-weighted imaging have been observed following surgery for infiltrating glioma. The purpose of this study was to investigate prospectively the incidence, time course, and ultimate outcome of these abnormalities. Forty-four consecutive patients with newly diagnosed gliomas were prospectively observed using serial MR imaging including diffusion-weighted sequences. Clinical and surgical data were also collected. Immediately postoperatively neuroimaging identified 28 patients (64%) in whom areas of reduced diffusion appeared in or around the resection cavity (mean volume 8.2 +/- 1.5 cm3). Complete resolution of this reduced diffusion was demonstrated within 90 days in 24 patients (86%). On subsequent neuroimages these areas demonstrated Gd enhancement as early as postoperative Day 15 and as late as Day 198 and ultimately took on the appearance of encephalomalacia in 26 (93%) of 28 cases. Postoperative reduced diffusion was not predicted by the clinical or surgical parameters that were assessed. No clinical deficits were attributable to the reduced diffusion. An abnormality related to diffusion-weighted sequences on postoperative MR imaging can occur after resection of newly diagnosed gliomas. In this study the abnormality typically resolved and was replaced by contrast enhancement on follow-up imaging, ultimately demonstrating encephalomalacia on long-term follow up. Findings on neuroimaging during the period of enhancement could be confused with recurrent tumor and interpreted as early treatment failure. Based on the findings of this study the authors strongly suggest that the inclusion of diffusion-weighted sequences in postoperative MR imaging is essential, as is MR imaging immediately before radiation therapy to monitor disease progression. A new enhancement observed after glioma surgery should be interpreted in the context of the diffusion-weighted image obtained immediately postoperatively.


Longitudinal Trajectory of Adolescent Exposure to Community Violence and Depressive Symptoms Among Adolescents and Young Adults: Understanding the Effect of Mental Health Service Usage.
Research on the impact of exposure to community violence tends to define victimization as a single construct. This study differentiates between direct and indirect violence victimization in their association with mental health problems and mental health service use. This study includes 8947 individuals from four waves of the National Longitudinal Study of Adolescent to Adult Health and examines (1) whether sub-types of adolescent victimization are linked to depressive symptoms; (2) whether adolescent victimization is linked with mental health service use; and (3) the role of mental health service use in attenuating symptoms arising from victimizations. Adolescents witnessing community violence were more likely to experience depressive symptoms during adolescence but not during their young adulthood; direct exposure to violence during adolescence does not predict depressive symptoms in adolescence but does in adulthood. Use of mental health service mediates report of depressive symptoms for adolescent witnessing community violence.


SFRP Tumour Suppressor Genes Are Potential Plasma-Based Epigenetic Biomarkers for Malignant Pleural Mesothelioma.
Malignant pleural mesothelioma (MPM) is associated with asbestos exposure. Asbestos can induce chronic inflammation which in turn can lead to silencing of tumour suppressor genes. Wnt signaling pathway can be affected by chronic inflammation and is aberrantly activated in many cancers including colon and MPM. SFRP genes are antagonists of Wnt pathway, and SFRPs are potential tumour suppressors in colon, gastric, breast, ovarian, and lung cancers and mesothelioma. This study investigated the expression and DNA methylation of SFRP genes in MPM cells lines with and without demethylation treatment. Sixty-six patient FFPE samples were analysed and have showed methylation of SFRP2 (56%) and SFRP5 (70%) in MPM. SFRP2 and SFRP5 tumour-suppressive activity in eleven MPM lines was confirmed, and long-term asbestos exposure led to reduced expression of the SFRP1 and SFRP2 genes in the mesothelium (MeT-5A) via epigenetic alterations. Finally, DNA methylation of SFRPs is detectable in MPM patient plasma samples, with methylated SFRP2 and SFRP5 showing a tendency towards greater abundance in patients. These data suggested that SFRP genes have tumour-suppresive activity in MPM and that methylated DNA from SFRP gene promoters has the potential to serve as a biomarker for MPM patient plasma.


Influence of neonatal thymectomy on blood pressure and hypertensive vascular disease in rats with renal hypertension.
The effect of neonatal thymectomy on the degree and prognosis of hypertension and on the vascular lesions in rats with renal hypertension was studied. There were no differences between thymectomized and sham operated hypertensive rats. The degree of hypertension, the frequency of spontaneous death and heart infarcts were the same in both groups. The occurrence and degree of perivascular cell infiltrations, deposits of perivascular connective tissue and fibrinoid degenerations of the media were found to be the same in both the thymectomized and the sham operated hypertensive animals. The results do not support the assumption that delayed type immune reactions are important in the pathogenesis of hypertensive vascular disease in renal hypertensive rats.


Inhibition of basal and pentagastrin-stimulated gastric acid secretion after treatment with benzilonium bromide and after selective proximal vagotomy.
50 consecutive patients with radiographically verified duodenal ulcer and a history of peptic ulcer disease for more than 3 years and with elevated gastric acid secretion in the basal state and after stimulation with pentagastrin were randomly allocated to two groups. The first group of 25 patients was treated with benzilonium bromide (Ulcoban Prolongatum, Parke, Davis & Co.) and the second group was subjected to selective proximal vagotomy (SPV). The patient's gastric acid secretion was determined before the start of treatment and after 1, 6, and 12 months. After one year the basal acid output had decreased by 58.2% in the group treated with benzilonium bromide and by 82.9% in the patients who had undergone SPV. The peak acid output fell by 49.4% in the benzilonium group and by 66.1% in the SPV group.


Potentials of Mangifera indica in the treatment of depressive-anxiety disorders: possible mechanisms of action.
Mangifera indica (Anacardiaceae) is an important herb in the traditional African and Ayurvedic medicines. The stem barks are used in the treatment of hypertension, insomnia, tumour, depression, rheumatism and as a tonic. This study was carried out to investigate antidepressant- and anxiolytic-like effect of the hydroethanol stem bark extract of M. indica (HeMI) in mice. HeMI (12.5-100 mg/kg, p.o.) was administered 1 h before subjecting the animal to the forced swim test (FST), tail suspension test (TST) and elevated plus maze tests (EPM). HeMI (12.5-100 mg/kg, p.o.) treatment produced significant reduction in immobility time [F(6.56)=8.35, p<0.001], [F(6,56)=7.55, p<0.001] in the FST and TST, respectively. Moreover, co-administration of sub-therapeutic doses of imipramine or fluoxetine with HeMI (3.125 mg/kg) elicited significant reduction in time spent immobile in the FST. However, pretreatment of mice with parachlorophenylalanine, metergoline, yohimbine or sulpiride abolished the antidepressant-like effect elicited by HeMI. In the EPM, HeMI produced significant [F(5,42)=8.91, p<0.001] increase in open arms exploration by 75.55 % and this effect was blocked by pretreatment of mice with flumazenil or metergoline. Findings from this study showed antidepressant-like effect of M. indica through interaction with 5-HT2 receptor, α2-adrenoceptor and dopamine D2-receptors. Also, an anxiolytic-like effect through its affinity for 5-HT2 and benzodiazepine receptors. Hence, M. indica could be a potential phytotherapeutic agent in the treatment of mixed anxiety-depressive illness.


Association Between Lipid Profile Measurements and Mortality Outcomes Among Older Adults in a Primary Care Setting: A Retrospective Cohort Study.
Background Lipid profile components play a role in predicting the development of cardiovascular disease and hence mortality, but recent studies have shown mixed results in the older population. The aim of our study was to investigate the association between levels of lipid profile components with all-cause mortality and cardiovascular outcomes among older adults in a primary care setting in Riyadh, Saudi Arabia. Methods A retrospective cohort study was performed among 485 individuals aged 60 years and older who visited the family medicine clinics linked to a tertiary care hospital during the first six months of 2010. The electronic charts of the participants were reviewed up to April 2022 to gather relevant data. Each lipid profile component, including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TGs), was categorized into four quartiles. LDL was calculated using the Friedewald formula. Cardiovascular outcomes included ischemic heart disease (IHD), heart failure (HF), and stroke. Results The mean follow-up period was 12 years. The elderly participants with the lowest HDL-C quartile (<1.1 mmol/L) were at higher risk of all-cause mortality (adjusted hazard ratio of 2.023 (95% CI 1.21-3.38)) and IHD (adjusted hazard ratio 3.2 (95% CI 1.6-6.2)). High TC (≥5.7 mmol/L) was associated with an increased risk of HF (adjusted hazard ratio 2.1 (95% CI 1.1-4.0)). Conclusion In patients aged 60 years and older, low HDL-C (<1.1 mmol/L) was associated with a higher risk for all-cause mortality and IHD, and high TC was associated with an increased risk of having HF. No significant association was found for LDL-C, TC, and TGs with all-cause mortality.


Parameters affecting degree of conversion of dual-cure resin cements in the root canal: FTIR analysis.
To evaluate the degree of conversion of dual-cured resin cements applied for luting of translucent and opaque fibre posts. Two dual-cured resin cements, RelyX ARC and Nexus 2, were used to cement 2 types of tooth-coloured fibre posts, D.T. Light-Post (translucent) and D.T. White-Post (opaque). The degree of conversion for each resin cement was measured. Post-curing polymerization and chemical curing of the cements were also measured. The degree of conversion was measured at various distances (4, 6 and 8 mm) from the tip of the light-curing unit by Fourier transform infrared spectroscopy. The data were analyzed with analysis of variance and post hoc tests (α = 0.05). The degree of conversion of the dual-cure cements was significantly higher with the D.T. Light-Posts than with the D.T. White-Posts (p < 0.05). No significant difference was observed in the degree of conversion at different depths for the RelyX ARC resin cement in conjunction with the D.T. Light-Posts (p > 0.05). The overall degree of conversion decreased linearly with increasing distance from the light-curing tip. Monitoring of post-curing polymerization and chemical curing revealed no further increase in degree of conversion after 5 minutes (p > 0.05). The translucent fibre posts (D.T. Light-Posts) allowed a significantly higher degree of conversion with dual-cure resin cements than the opaque fibre posts (D.T. White-Posts) because of the light-transmitting property of their optical fibres.


Dinuclear palladium(ii) complexes with bridging amidate ligands.
New homonuclear dimeric Pd(ii) complexes have been synthesized by the reaction of Pd(en)(2+) or Pd(bipy)(2+) (where en = ethylenediamine and bipy = 2,2'-bipyridine) units with acetamide or by the Pd(ii) mediated hydrolysis of CH(3)CN. In these dimers the two metal centers are bridged by either two amidates or by the combination of one hydroxo group and one amidate ligand. The crystal structures of complexes {[Pd(bipy)](2)(micro-1,3-CH(3)CONH)(2)}(NO(3))(2).H(2)O.1/2(CH(3))(2)CO.1/2CH(3)CN () and {[Pd(bipy)](2)(micro-1,3-CH(3)CONH)(2)}(OTf)(2) () showed intrametallic Pd-Pd distances of 2.8480(8) A () and 2.8384(7) A (), respectively, in accordance with the accepted values for a strong Pd-Pd interaction. The presence of pi[dot dot dot]pi interactions between the bipyridine ligands on the di-micro-amidate complexes of Pd(bipy)(2+) shortens the distance between the two Pd centers and allows the formation of the metal-metal interaction. By contrast, the crystal structure of complex {[Pd(en)](2)(micro-1,3-CH(3)CONH)(2)}(OTf)(2).H(2)O (), (where OTf = triflate) where there is no pi[dot dot dot]pi interaction between the ligands on the metal centers, is also reported, and no Pd-Pd interaction is observed. Additionally, one of the complexes, {[Pd(en)](2)(micro-OH)(micro-CH(3)CONH)}(NO(3))(2) (), presents an interesting hydrogen bonded 3-D network formed by nitrate ions and water molecules. All complexes have been characterized by infrared and (1)H NMR spectroscopy.


History of Cardiothoracic Surgery at New York University.
This monograph outlines the rich history of cardiothoracic surgery at New York University (NYU), beginning with its origins at The Bellevue Hospital in the mid-1800's. Numerous early clinical accomplishments were significant, leading up to the arrival of Dr Frank Spencer in 1966. Under Dr Spencer's leadership, the department progressed with development of a culture of innovation, leadership and education that carries through today. The program encompasses three major hospitals and will soon graduate its 50th class of trainees, many of whom have had outstanding careers and a major impact on the field of cardiothoracic surgery. This culture continues under the direction of our current chair, Dr Aubrey Galloway, whose vision has orchestrated and refined a new period of innovation and excellence.


Droplet displacements and oscillations induced by ultrasonic surface acoustic waves: a quantitative study.
We present an experimental study of a droplet interacting with an ultrasonic surface acoustic wave. Depending on the amplitude of the wave, the drop can either experience an internal flow with its contact line pinned, or (at higher amplitude) move along the direction of the wave also with internal flow. Both situations come with oscillations of the drop free surface. The physical origins of the internal mixing flow as well as the drop displacement and surface waves are still not well understood. In order to give insights of the underlying physics involved in these phenomena, we carried out an experimental and numerical study. The results suggest that the surface deformation of the drop can be related to a combination between acoustic streaming effect and radiation pressure inside the drop.


Analysis of Immune Gene Expression Subtypes Reveals Osteosarcoma Immune Heterogeneity.
Osteosarcoma (OS) patients have a poor response to immunotherapy due to the sheer complexity of the immune system and the nuances of the tumor-immune microenvironment. Methodology. To gain insights into the immune heterogeneity of OS, we identified robust clusters of patients based on the immune gene expression profiles of OS patients in the TARGET database and assessed their reproducibility in an independent cohort collected from the GEO database. The association of comprehensive molecular characterization with reproducible immune subtypes was accessed with ANOVA. Furthermore, we visualized the distribution of individual patients in a tree structure by the graph structure learning-based dimensionality reduction algorithm. We found that 87 OS samples can be divided into 5 immune subtypes, and each of them was associated with distinct clinical outcomes. The immune subtypes also demonstrated widely different patterns in tumor genetic aberrations, tumor-infiltrating, immune cell composition, and cytokine profiles. The immune landscape of OS uncovered the significant intracluster heterogeneity within each subtype and depicted a continuous immune spectrum across patients. The established five immune subtypes in our study suggested immune heterogeneity in OS patients and may provide optimal individual immunotherapy for patients exhibiting OS.


Impact of Martial Arts (Judo, Karate, and Kung Fu) on Bone Mineral Density Gains in Adolescents of Both Genders: 9-Month Follow-Up.
To compare bone mineral density (BMD) gains in adolescents of both genders stratified according to different martial art styles in a 9-month follow-up study. The longitudinal study consisted of 29 adolescents of both genders and age between 11 and 17 years stratified into a control group (not engaged in any sport) and 50 fighters (kung fu/karate, n = 29; judo, n = 21). All 79 subjects underwent anthropometric measures (weight, height, leg length, and height set) and dual-energy X-ray absorptiometry (BMD, in g/cm2) at 2 moments, baseline and 9 months later. Maturity offset (age at peak height velocity), lean soft tissue, chronological age, and resistance training were treated as covariates. Male judoists presented higher gains in BMD-spine [0.098 g/cm2 (95% confidence interval, 0.068-0.128)] than control group [0.040 g/cm2 (95% confidence interval, 0.011-0.069)] (post hoc test with P = .030). There was no effect of martial art on BMD gains among girls. Independently of gender, in all multivariate models, lean soft tissue constituted the most relevant covariate. Judo practice in adolescents affected the bone accrual significantly after 9-month follow-up compared with controls, mainly in boys.


An Alternative Approach to the Effects of Multiple Traumas: Complex Post-Traumatic Stress Disorder.
Exposure to multiple traumatic events, particularly in childhood, has been shown to result in more complex symptoms than those seen after exposure to a single traumatic event. In case of overlooking the link between trauma and psychopathology, patients with multiple traumatic experiences receive a variety of different diagnoses that are unable to completely cover the clinical picture. Misdiagnoses of genuine cases inevitably lead to mistreatment. A diagnosis of complex post-traumatic stress disorder has been proposed to cover the emerging psychopathology in survivors of multiple traumas. This present report aimed to discuss the construct and to increase the awareness of complex post-traumatic stress disorder diagnosis among mental health professionals.


Comparison of flap adhesion strength using the Amadeus microkeratome and the IntraLase iFS femtosecond laser in rabbits.
To compare adhesion strength of flaps created with a mechanical microkeratome and the IntraLase femtosecond laser as well as to analyze the effect of different side-cut configurations. A flap was created in four groups of New Zealand white rabbits--microkeratome group (Amadeus II microkeratome, Ziemer Group AG [5 eyes; 9-mm suction ring and 140-microm head]), and three IntraLase groups (IntraLase iFS 150 kHz femtosecond laser, AMO Inc [9-mm diameter and 120-microm flap each]): normal energy side-cut (4 eyes; side-cut angle 70 degrees, side-cut energy 0.8 microJ); high energy side-cut (4 eyes; side-cut angle 70 degrees, side-cut energy 1.6 microJ); and inverted side-cut (4 eyes; side-cut angle 140 degrees, side-cut energy 0.8 microJ). Flap adhesion strength was measured 75 days after surgery using a tension meter to dehisce the flaps. In the microkeratome group, mean force was 210+/-89 g (range: 151 to 360 g); 492+/-46 g (range: 439 to 540 g) in the normal energy side-cut group; 444+/-13 g (range: 426 to 455 g) in the high energy side-cut group; and 687+/-105 g (range: 552 to 797 g) in the inverted side-cut group. Differences between the microkeratome and all IntraLase groups were highly significant (P=.001), and differences between the inverted side-cut group and the standard 70 degrees side-cut groups were statistically significant (P=.01). Flap adhesion is significantly stronger with the IntraLase femtosecond laser than with the Amadeus mechanical microkeratome, and an inverted side-cut increases flap adhesion significantly compared with a standard side-cut.


Abdominal compartment syndrome.
To invstigte the physiologic effects and therapeutic management ofthe abdominal kompartm sendrome (ACS) METHODS: A review ofthe recent Iiterature, experiences and opinions ofthe author are expressed in the papei: Intraabdominal bleeding, peritonitis, ileus, shock-reperfusion syndrome, intestinal edema, Iaparoscopic procedures with gas, ciosure ofthe abdomen in spite ofincreased pressure and burns are some ofthefactors that take place in etiology. The critical intrabdominal pressure value that requires decompression is debatable. In patients with high abdominal pressures, the pressure should be decreased with Iaparotomy immediately and the abdomen should not be ciosed primarily. These measures will help us to Iower the rates of mortality and morbidity and improve the quality ofhealth services.


Phospholipid methylation and biological signal transmission.
Many types of cells methylate phospholipids using two methyltransferase enzymes that are asymmetrically distributed in membranes. As the phospholipids are successively methylated, they are translocated from the inside to the outside of the membrane. When catecholamine neurotransmitters, lectins, immunoglobulins or chemotaxic peptides bind to the cell surface, they stimulate the methyltransferase enzymes and reduce membrane viscosity. The methylation of phospholipids is coupled to Ca2+ influx and the release of arachidonic acid, lysophosphatidylcholine, and prostaglandins. These closely associated biochemical changes facilitate the transmission of many signals through membranes, resulting in the generation of adenosine 3',5'-monophophate in many cell types, release of histamine in mast cells and basophils, mitogenesis in lymphocytes, and chemotaxis in neutrophils.


Healthy People 2010: implications for orthopaedic nurses.
Healthy People 2010 is the latest publication developed by the United States Public Health Service (USDHSS, 2000) to identify the most significant and preventable threats to health and to establish national goals to reduce these threats. This document contains two major goals, 467 objectives, 28 focus areas, and 10 leading indicators. Orthopaedic nurses are in ideal positions to assume leadership roles in promoting healthier behaviors in neighborhoods and communities as individuals, groups, and organizations begin to incorporate Healthy People 2010 into health promotion planning. Healthy People 2010 is designed to be a valuable resource for participating most effectively in improving the nation's health. By using this document to plan health promotion and disease prevention programs, orthopaedic nurses, regardless of practice setting, can impact the health of future generations of Americans.


Glucocorticoid receptor gene, low-grade inflammation, and heart failure: the Heart and Soul study.
A common haplotype of the glucocorticoid receptor (GR) gene has been associated with increased susceptibility to coronary heart disease (CHD). Whether this haplotype predisposes to heart failure (HF) is unknown. The objective of the study was to determine whether GR haplotype 3 is associated with HF and whether this association is explained by low-grade inflammation (C-reactive protein). In a prospective cohort study, participants were genotyped for common GR gene polymorphisms (ER22/23EK, BclI C/G, N363S, 9beta A/G). Haplotype analyses were conducted. The study was conducted at one university medical center, two Veterans Affairs medical centers, and nine public health clinics. Patients included 526 white outpatients with stable CHD. Echocardiographic evidence of ventricular dysfunction, self-reported heart failure, and subsequent hospitalization for heart failure were measured. After adjusting for age, sex, smoking, and body mass index, participants with two copies of haplotype 3 were more likely than those with 0 or 1 copy to report heart failure [hazard ratio (HR) 4.15, 95% confidence interval (CI) 1.5-11.3, P < 0.01], have systolic dysfunction (left ventricular ejection fraction <50%) (HR 3.0, 95% CI 0.9-9.9, P = 0.07), and be hospitalized for HF during a mean follow-up of 6 yr (HR 3.0, 95% CI 1.3-7.0, P = 0.01). These associations were attenuated after adjustment for higher C-reactive protein levels in patients with two copies of haplotype 3. We found that the GR gene haplotype 3 was associated with prevalent HF, systolic dysfunction, and subsequent HF hospitalization in patients with CHD. This association was partly mediated by low-grade inflammation.


Research of areal density diagnostic technique on Shenguang III laser prototype facility.
In the test run of Shenguang III laser prototype facility, under the low density condition, the yield ratio method was used to measure the fuel areal density. Considering the uncertainty of the neutron yield, detectors with different efficiencies were used. The clear secondary-neutron signals in inertial confinement fusion experiments were obtained for the first time in China, and the values of the areal density were deduced.


Thymic and pulmonary mucosa-associated lymphoid tissue lymphomas.
A 52-year-old woman with no history of autoimmune disease was found to have a mediastinal tumor and focal airspace opacity in the right lung. Tissue diagnosis was obtained by resection of the mediastinal tumor and open fine needle aspiration of the right pulmonary tissue through a median sternotomy. Histopathologic examination and immunohistochemistry of the thymus tumor and cytologic analysis of the pulmonary tissue were both consistent with mucosa-associated lymphoid tissue (MALT) lymphoma. This case suggests that multiorgan MALT lymphoma can also develop in the absence of an autoimmune disease such as Sjogren's syndrome.


Squamous Cell Carcinoma of the Lung Presenting Unilateral Thoracic Hyperhidrosis: A Case Report and Review of Literature.
Unilateral hyperhidrosis is an uncommon manifestation, and the majority of cases have been attributed to neurological diseases. There are few cases of unilateral hyperhidrosis associated with thoracic malignant tumors. We herein report a 74-year-old Japanese man with squamous cell carcinoma of the lung who presented with unilateral hyperhidrosis in the right thoracic area as one of the first clinical manifestations. We should consider the possibility of pleural diseases, including metastatic lung cancer, when encountering patients presenting with unilateral thoracic hyperhidrosis.


Lactic acid bacterial cell factories for gamma-aminobutyric acid.
Gamma-aminobutyric acid is a non-protein amino acid that is widely present in organisms. Several important physiological functions of gamma-aminobutyric acid have been characterized, such as neurotransmission, induction of hypotension, diuretic effects, and tranquilizer effects. Many microorganisms can produce gamma-aminobutyric acid including bacteria, fungi and yeasts. Among them, gamma-aminobutyric acid-producing lactic acid bacteria have been a focus of research in recent years, because lactic acid bacteria possess special physiological activities and are generally regarded as safe. They have been extensively used in food industry. The production of lactic acid bacterial gamma-aminobutyric acid is safe and eco-friendly, and this provides the possibility of production of new naturally fermented health-oriented products enriched in gamma-aminobutyric acid. The gamma-aminobutyric acid-producing species of lactic acid bacteria and their isolation sources, the methods for screening of the strains and increasing their production, the enzymatic properties of glutamate decarboxylases and the relative fundamental research are reviewed in this article. And the potential applications of gamma-aminobutyric acid-producing lactic acid bacteria were also referred to.


Significant Remodeling Affects the Circulating Glycosaminoglycan Profile in Adult Patients with both Severe and Mild Forms of Acute Pancreatitis.
Acute pancreatitis (AP) manifests itself either as a mild, self-limiting inflammation or a severe, systemic inflammatory process that is associated with various complications and a high mortality rate. It is unknown whether these two forms of the disease can differ in the profile of circulating glycosaminoglycans, which are molecules with huge biological reactivity due to a high density of negative electric charge. Plasma glycosaminoglycans were characterized/quantified in 23 healthy controls, 32 patients with mild AP, and 15 individuals with severe disease using electrophoresis with enzymatic identification (chondroitin sulfate and heparan sulfate) or an ELISA-based test (hyaluronan). Moreover, the correlations between the glycosaminoglycan levels and clinical parameters were evaluated. Both forms of AP showed similar remodeling of the plasma profile of the sulfated glycosaminoglycans. In contrast, only in the patients with mild AP was the level of circulating hyaluronan significantly decreased as compared to the healthy controls. Both forms of AP are associated with systemic changes in the metabolism of glycosaminoglycans. However, the alterations in hyaluronan metabolism may contribute to the disease evolution. The circulating hyaluronan may have some clinical value to predict the severity of AP and to evaluate the clinical status of patients with severe AP.


ARL4C might serve as a prognostic factor and a novel therapeutic target for gastric cancer: bioinformatics analyses and biological experiments.
The ADP-ribosylation factor-like proteins (ARLs) have been proved to regulate the malignant phenotypes of several cancers. However, the exact role of ARLs in gastric cancer (GC) remains elusive. In this study, we systematically investigate the expression status, interactive relations, potential pathways, genetic variations and clinical values of ARLs in GC. We find that ARLs are significantly dysregulated in GC and involved in various cancer-related pathways. Subsequently, machine learning models identify ARL4C as one of the two most significant clinical indicators among ARLs for GC. Furthermore, ARL4C silencing remarkably inhibits the growth and metastasis of GC cells both in vitro and in vivo. Moreover, enrichment analysis indicates that ARL4C is highly correlated with TGF-β1 signalling. Correspondingly, TGF-β1 treatment dramatically increases ARL4C expression and ARL4C knockdown inhibits the phosphorylation level of Smads, downstream factors of TGF-β1. Meanwhile, the coexpression of ARL4C and TGF-β1 worsens the prognosis of GC patients. Our work comprehensively demonstrates the crucial role of ARLs in the carcinogenesis of GC and the specific mechanisms underlying the GC-promoting effects of TGF-β1. More importantly, we uncover the great promise of ARL4C-targeted therapy in improving the efficacy of TGF-β1 inhibitors for GC patients.


[Analysis of lymph node metastasis pattern in gastric cancer patients at stage pN1].
To investigate the lymph node metastasis pattern in pN1 stage gastric cancer patients and to analyze its risk factors. Clinicopathological data of 219 patients who underwent radical gastrectomy and were confirmed as pN1 stage gastric cancer between January 2013 and March 2016 were reviewed. All the patients underwent D2 or extended D2(D2+) lymphadenectomy. The overall metastatic rate was calculated. The risk factors associated with lymph node metastasis were analyzed. The pattern of skip lymph node metastasis and clinicopathological factors related to skip metastasis were analyzed. Among 219 patients, 119 patients had only one metastatic lymph node, and 100 patients had two metastatic lymph nodes. The relatively higher sites of lymph node metastasis were station No.3[29.2%(64/219)], No.6[18.3%(40/219)] and No.4[11.4%(25/219)]. Compared to patients with tumor diameter ≤5 cm, metastatic rates of station No.3[39.4% (39/99) vs. 20.8%(25/120), P=0.003], No.4[16.2%(16/99) vs. 7.5%(9/120), P=0.045] and No.8[16.2%(16/99) vs. 6.7%(8/120), P=0.025] were significantly higher in those with tumor diameter >5 cm. Skip lymph node metastasis was detected in 56 cases(25.6%) and skip lymph node metastatic rate was significantly higher in patients with tumor diameter >5 cm [34.3%(34/99) vs. 18.3%(22/120), P=0.007]. Logistic regression analysis showed that the tumor size was an independent risk factor for the skip lymph node metastasis in pN1 stage gastric cancer (OR=1.982, 95%CI: 0.978 to 3.921, P=0.033). The perigastric station No1 lymph node is the main site of early lymph node metastasis of pN1 stage gastric cancer. General pattern of lymph node metastasis is from proximus to distance, while quite a lot of skip lymph node metastases are observed. Tumor size is an important factor affecting the lymph node metastasis and bigger tumor may result in skip lymph node metastasis easily.


Spatial coding and response redundancy in parallel visual pathways of the marmoset Callithrix jacchus.
Many neurons in the primary visual cortex (area V1) show pronounced selectivity for the orientation and spatial frequency of visual stimuli, whereas most neurons in subcortical afferent streams show little selectivity for these stimulus attributes. It has been suggested that this transformation is a functional sign of increased coding efficiency, whereby the redundancy (or overlap in response properties) is reduced at consecutive levels of visual processing. Here we compared experimentally the response redundancy in area V1 with that in the three main dorsal thalamic afferent streams, the parvocellular (PC), koniocellular (KC), and magnocellular (MC) divisions of the dorsal lateral geniculate nucleus (LGN) in marmosets. The spatial frequency and orientation tuning of single cells in the LGN and area V1 were measured, using luminance contrast sine-wave gratings. A joint spatial frequency-orientation response selectivity profile was calculated for each cell. Response redundancy for each population was estimated by cross-multiplication of the joint selectivity profiles for pairs of cells. We show that when estimated in this way, redundancy in LGN neurons is approximately double that of neurons in cortical area V1. However, there are differences between LGN subdivisions, such that the KC pathway has a spatial representation that lies between the redundant code of the PC and MC pathways and the more efficient sparse spatial code of area V1.


Pro- and Anti-fibrogenic Functions of Gram-Negative Bacterial Lipopolysaccharide in the Liver.
Extensive research performed over several decades has identified cells participating in the initiation and progression of fibrosis, and the numerous underlying inter- and intra-cellular signaling pathways. However, liver fibrosis continues to be a major clinical challenge as the precise targets of treatment are still elusive. Activation of physiologically quiescent perisinusoidal hepatic stellate cells (HSCs) to a myofibroblastic proliferating, contractile and fibrogenic phenotype is a critical event in the pathogenesis of chronic liver disease. Thus, elucidation of the mechanisms of the reversal to quiescence or inhibition of activated HSCs, and/or their elimination via apoptosis has been the focus of intense investigation. Lipopolysaccharide (LPS), a gut-resident Gram-negative bacterial endotoxin, is a powerful pro-inflammatory molecule implicated in hepatic injury, inflammation and fibrosis. In both acute and chronic liver injury, portal venous levels of LPS are elevated due to increased intestinal permeability. LPS, via CD14 and Toll-like receptor 4 (TLR4) and its adapter molecules, stimulates macrophages, neutrophils and several other cell types to produce inflammatory mediators as well as factors that can activate HSCs and stimulate their fibrogenic activity. LPS also stimulates synthesis of pro- and anti-inflammatory cytokines/chemokines, growth mediators and molecules of immune regulation by HSCs. However, LPS was found to arrest proliferation of activated HSCs and to convert them into non-fibrogenic phenotype. Interestingly, LPS can elicit responses in HSCs independent of CD14 and TLR4. Identifying and/or developing non-inflammatory but anti-fibrogenic mimetics of LPS could be relevant for treating liver fibrosis.


Clinical efficacy of modified sacral fixation under Leonardo da Vinci robot laparoscopy for pelvic organ prolapse.
The aim of this study was to analyze the clinical efficacy of modified sacral fixation under Leonardo da Vinci robot laparoscopy for pelvic organ prolapse (POP). Sixty POP patients admitted to our hospital from January 2020 to December 2021 were picked and divided into Group A (laparoscopic Y-mesh, n = 20), Group B (laparoscopic sacrovaginal fixation, n = 20), and Group C (da Vinci robotic sacral fixation, n = 20). These three groups were compared in terms of the perioperative indexes, such as operation time, intraoperative blood loss, postoperative indwelling catheter days, anal exhaust time, postoperative hospitalization days, etc. The occurrence of short-term and long-term complications in the three groups was compared. The changes of the following index values in the POP quantification system (POP -Q) staging before and 1 year after surgery were recorded and compared among the three groups. It mainly includes the midline of the anterior vaginal wall at 3 cm from the hymenal margin (Aa), the farthest point of the anterior vaginal vault from point Aa (Ba), the farthest point of the ectocervix (C), the location of the posterior vaginal vault or rectal uterine trap (D), the midline of the posterior vaginal wall at 3 cm from the hymenal margin (Ap), and the reflection of the posterior vaginal vault at the farthest point from the Ap point (Bp) values. The changes in Pelvic Floor Distress Inventory-Short Form 20 (PFDI-20) and Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12) were recorded and compared before and 1 year after the operation. The patients in Group C had significantly lower intraoperative bleeding, postoperative indwelling catheter days, anal exhaust time, and postoperative hospitalization days compared with those in Group A and Group B (p < 0.05). There existed no statistical difference in the incidence of short-term and long-term complications between Group B and Group C (p > 0.05), but both were much lower than Group A (p < 0.05). The differences in POP-Q staging, PFDI-20 scale, and PISQ-12 scale were not statistically significant among the three groups before surgery (p > 0.05), and the POP-Q staging Aa, Ba, C, D, Ap, and Bp values, PFDI-20 scale, and PISQ-12 scale were strongly improved in three groups after the surgery (p < 0.05). However, the POP-Q staging, PFDI-20 scale, and PISQ-12 scale among the three groups had no obvious difference after the surgery (p > 0.05). The efficacy of modified sacral fixation under Leonardo da Vinci robot laparoscopy for POP was comparable to that of laparoscopic Y-mesh treatment and laparoscopic sacral vaginal fixation. However, da Vinci's robotic sacral fixation had the advantages of less intraoperative bleeding and faster postoperative recovery, which helped patients recover quickly and improved their quality of life.


Transcriptomic changes following synthesis of a Populus full-sib diploid and allotriploid population with different heterozygosities driven by three types of 2n female gamete.
Diploid gametes are usually applied to produce triploids of Populus [originating from first-division restitution (FDR), second-division restitution (SDR), and postmeiotic restitution (PMR) 2n eggs]. Three types of 2n gametes transmitted different parental heterozygosities in Populus. Failed spindle formation and no chromosomal separation to opposite poles during meiosis I mean that FDR 2n gametes carry nonsister chromatids that are potentially heterozygous. By contrast, SDR 2n gametes result from failed sister chromatid separation in meiosis II, and therefore, they carry sister chromatid that are potentially homozygous. Completely homozygous 2n gametes can arise from the PMR mechanism. The alteration of gene expression resulting from allopolyploidization is a prominent feature in plants. We compared gene expression in the full-sib progeny of three allotriploid Populus populations (triploid-F, triploid-S, and triploid-P) with that in its parent species, and their full-sib diploid F1 hybrid. Genome-wide expression level dominance was biased toward the maternal in the diploid F1 hybrid and three allotriploid populations, whereas our data indicated important, but different, effects of the transmission of different heterozygosity by 2n female gametes in the expression patterns of allopolyploids. Because of the higher level of heterozygosity, the triploids had higher rates of non-additive and transgressive expression patterns in the triploid-F than in triploid-S and triploid-P. Compared with diploid F1, about 30-fold more genes (251) were differently expressed in the triploid-F than in the triploid-S (9) and triploid-P (8), respectively. These findings indicate that hybridization and polyploidization have immediate and distinct effects on the large-scale patterns of gene expression, and different effects on the transmission of heterozygosity by three 2n female gametes.