The "House of Quality for Behavioral Science"-a user-centered tool to design behavioral interventions.
Within the behavioral field, a plethora of conceptual frameworks and tools have been developed to improve transition from efficacy to effectiveness trials; however, they are limited in their ability to support new, iterative intervention design decision-making methodologies beyond traditional randomized controlled trial design. Emerging theories suggest that researchers should employ engineering based user-centered design (UCD) methods to support more iterative intervention design decision-making in the behavioral field. We present, an adaptation of a UCD tool used in the engineering field-the Quality Function Deployment "House of Quality" correlation matrix, to support iterative intervention design decision-making and documentation for multicomponent behavioral interventions and factorial trial designs. We provide a detailed description of the adapted tool-"House of Quality for Behavioral Science", and a step-by-step use-case scenario to demonstrate the early identification of intervention flaws and prioritization of requirements. Four intervention design flaws were identified via the tool application. Completion of the relationship correlation matrix increased requirement ranking variance for the researcher (σ2 = 0.47 to 7.19) and participant (σ2 = 0.56 to 3.89) perspective. Requirement prioritization (ranking) was facilitated by factoring in the strength of the correlation between each perspective and corresponding importance. A correlational matrix tool such as the "House of Quality for Behavioral Science" may provide a structured, UCD approach that balances researcher and participant needs and identifies design flaws for pragmatic behavioral intervention design. This tool may support iterative design decision-making for multicomponent and factorial trial designs.


Evaluation of Cassia tora Linn. against Oxidative Stress-induced DNA and Cell Membrane Damage.
The present study aims to evaluate antioxidants and protective role of Cassia tora Linn. against oxidative stress-induced DNA and cell membrane damage. The total and profiles of flavonoids were identified and quantified through reversed-phase high-performance liquid chromatography. In vitro antioxidant activity was determined using standard antioxidant assays. The protective role of C. tora extracts against oxidative stress-induced DNA and cell membrane damage was examined by electrophoretic and scanning electron microscopic studies, respectively. The total flavonoid content of CtEA was 106.8 ± 2.8 mg/g d.w.QE, CtME was 72.4 ± 1.12 mg/g d.w.QE, and CtWE was 30.4 ± 0.8 mg/g d.w.QE. The concentration of flavonoids present in CtEA in decreasing order: quercetin >kaempferol >epicatechin; in CtME: quercetin >rutin >kaempferol; whereas, in CtWE: quercetin >rutin >kaempferol. The CtEA inhibited free radical-induced red blood cell hemolysis and cell membrane morphology better than CtME as confirmed by a scanning electron micrograph. CtEA also showed better protection than CtME and CtWE against free radical-induced DNA damage as confirmed by electrophoresis. C. tora contains flavonoids and inhibits oxidative stress and can be used for many health benefits and pharmacotherapy.


Early discharge as a mediator of greater ICU-level care requirements in patients not enrolled on the AAML0531 clinical trial: a Children's Oncology Group report.
Previous data suggest that patients enrolled on clinical trials for treatment of cancer have better overall survival than patients who do not enroll; however, short-term outcomes relative to trial enrollment and corresponding mediators have not been assessed. A cohort of pediatric patients with newly-diagnosed acute myeloid leukemia was assembled from the Pediatric Health Information System. We evaluated whether patients not enrolled onto Children's Oncology Group trial AAML0531 had greater intensive care unit (ICU)-level requirements than enrolled patients and whether early discharge after chemotherapy administration mediated this association. Patients not enrolled on AAML0531 were more likely to be discharged early (aOR = 1.40, 95% confidence interval [CI]: 1.02, 1.90) and to require ICU-level care (aOR = 2.00, 95% CI: 1.06, 3.78) than enrolled patients, but early discharge explained only a small proportion (12.3%) of the absolute difference in ICU-level care risk. The direct effect of nonenrollment on the need for ICU-level care was significant (aOR = 1.89, 95% CI: 1.00, 3.94), whereas the indirect effect mediated through early discharge was not (aOR = 1.07, 95% CI: 0.95, 1.19). Factors other than postchemotherapy discharge strategy drive the difference in ICU utilization by trial enrollment status.


Reduction of circulating microemboli in the subclavian vein of patients undergoing haemodialysis using pre-filled instead of dry dialysers.
Chronic microembolization that can be demonstrated by pulsed Doppler ultrasound may give rise to pulmonary side-effects during haemodialysis by direct vessel obstruction, increased complement activation or platelet aggregation. The objective of the present investigation was to study whether the use of pre-filled instead of dry dialysers would help to minimize the number of microemboli. The study cohort consisted of 23 patients undergoing maintenance haemodialysis. Using a 2 MHz pulsed ultrasound device, the subclavian vein downstream to the dialysis fistula was investigated for 10 min during the dialysis session. The ultrasound examination was performed twice during two successive dialysis sessions, using a pre-filled or a dry dialyser in randomized order. In all patients investigated, numerous microembolic signals (MES) could be observed in the subclavian vein. Treatment with pre-filled dialysers was associated with significantly less MES (82 +/- 94) as compared with dry dialysers (268 +/- 296; P = 0.002). In comparison to dry dialysers, the use of pre-filled dialysers leads to a significant reduction in microembolization, which may prevent repeated damage to the pulmonary vasculature and, thus, cause less pulmonary damage.


Diagnosis and treatment of orbital hemorrhagic lesions.
Orbital hemorrhagic lesions include a group of heterogeneous conditions that may be idiopathic or caused by trauma, surgery, or preexisting vascular tumors or malformations. We report clinical, computed tomographic, and magnetic resonance imaging features of eight cases of orbital hemorrhage (2 cystic lymphangiomas, 2 subperiosteal hematomas, 1 traumatic hematoma, 1 hemorrhagic varix, 1 cholesterol granuloma, and 1 postsurgical hemosiderin deposit). The differential diagnosis of orbital hemorrhagic lesions may be difficult because of their relative rarity and nonspecific presentation. In particular, on computed tomography, cholesterol granulomas may simulate a lacrimal gland epithelial tumor and subperiosteal hematomas, a lymphoid tumor. Magnetic resonance imaging is an ideal imaging technique because of its ability to identify blood and blood products in all stages of degradation. Treatment can be limited to observation in varices, lymphangiomas, and trauma if vision is not threatened; otherwise, surgical blood drainage should be attempted. Cholesterol granulomas are best treated by curettage through an extraperiosteal orbitotomy. For subperiosteal acute or subacute hemorrhages, surgical drainage is recommended if the blood is not spontaneously reabsorbed within a few weeks.


Spatial-MGCN: a novel multi-view graph convolutional network for identifying spatial domains with attention mechanism.
Recent advances in spatial transcriptomics technologies have enabled gene expression profiles while preserving spatial context. Accurately identifying spatial domains is crucial for downstream analysis and it requires the effective integration of gene expression profiles and spatial information. While increasingly computational methods have been developed for spatial domain detection, most of them cannot adaptively learn the complex relationship between gene expression and spatial information, leading to sub-optimal performance. To overcome these challenges, we propose a novel deep learning method named Spatial-MGCN for identifying spatial domains, which is a Multi-view Graph Convolutional Network (GCN) with attention mechanism. We first construct two neighbor graphs using gene expression profiles and spatial information, respectively. Then, a multi-view GCN encoder is designed to extract unique embeddings from both the feature and spatial graphs, as well as their shared embeddings by combining both graphs. Finally, a zero-inflated negative binomial decoder is used to reconstruct the original expression matrix by capturing the global probability distribution of gene expression profiles. Moreover, Spatial-MGCN incorporates a spatial regularization constraint into the features learning to preserve spatial neighbor information in an end-to-end manner. The experimental results show that Spatial-MGCN outperforms state-of-the-art methods consistently in several tasks, including spatial clustering and trajectory inference.


Penicillilactone A, a novel antibacterial 7-membered lactone derivative from the sponge-associated fungus Penicillium sp. LS54.
One novel 7-membered lactone derivative, penicillilactone A (1), together with two known compounds, rugulosin A (2) and rugulosin (3) were isolated from the sponge-derived fungus Penicillium sp. LS54. Their structures were elucidated on the basis of spectroscopic analysis and comparison with literature data. Remarkably, penicillilactone A (1) is the first natural product containing a 7-membered lactone ring fused with a furan core. Penicillilactone A (1) exhibited moderate antibacterial activity against aquatic pathogen Vibrio harveyi with an MIC value of 8 μg/mL.


Neurobehavioral effects of obstructive sleep apnea: an overview and heuristic model.
Obstructive sleep apnea can cause significant daytime behavioral and adaptive deficits, conventionally called 'neurobehavioral' because they are presumed to be mediated by the brain. The past few years have witnessed a marked increase in research into the neurobehavioral effects of obstructive sleep apnea, making it difficult for researchers and clinicians to stay abreast of the field. This article summarizes recent findings on the neurobehavioral effects of adult and pediatric obstructive sleep apnea, and presents a heuristic model to guide future research and clinical conceptualizations. Recent publications have suggested overlapping but distinct neurobehavioral deficits that tend to accompany obstructive sleep apnea in the adult versus childhood years. There have been exciting new developments into the mechanisms by which obstructive sleep apnea may result in these deficits, including findings based upon advanced neuroimaging tools and carefully controlled animal research. There has also been accumulating evidence for potential moderators of morbidity; that is, factors that alter the nature or severity of neurobehavioral deficit resulting from obstructive sleep apnea. Task- and context-related factors that may affect outcome have been identified, as have potential markers for individual risk and resiliency. The relation between obstructive sleep apnea and neurobehavioral deficit is probably not dependent on a single mediating mechanism, nor is it invariant across individuals. In outlining several potential moderating factors, the model presented here was designed to provide a guide for future research and a way of thinking about obstructive sleep apnea that better captures the wide variation in neurobehavioral outcome seen by practicing clinicians.


Antimicrobial susceptibility of invasive group B streptococcal isolates from south-west Sweden 1988-2001.
The antibiotic susceptibility of 297 invasive isolates of group B streptococci (GBS) to a panel of 12 antibiotics was analysed using the E-test. The isolates (from 123 neonates and 174 adults) were collected from south-west Sweden during the 2 periods 1988-1997 and 1998-2001. The breakpoints of the Clinical and Laboratory Standards Institute were used. All isolates were sensitive to cefotaxime, meropenem, linezolid, vancomycin, moxifloxacin and quinupristin-dalfopristin. Two strains displayed a slightly decreased susceptibility to penicillin G (MIC 0.25 microg/ml) also when tested by the broth dilution method. Two per cent were resistant to erythromycin and 1% to clindamycin. Strains with intermediate sensitivity to erythromycin and clindamycin increased over the 2 study periods. 68% were resistant to doxycycline, and the resistance rate for doxycycline increased over the 2 study periods. No strain was resistant to trimethoprim-sulfamethoxazole. Serotype V dominated among strains with intermediate susceptibility to erythromycin and clindamycin. There were no other relationships between serotypes and decreased sensitivity to any agent. There were no significant differences in susceptibility to any agent tested between strains isolated from neonates and adults. In conclusion, penicillins remain the drug of choice in the region but with the increasing rates of intermediate susceptibility to both erythromycin and clindamycin, antibiotic sensitivity analysis should be performed on the GBS isolates from penicillin-allergic patients.


Effects of polypeptide growth factors on mandibular condylar cartilage of the rat in vitro.
In a comparative study, the influence of several polypeptide growth factors on proliferation and matrix synthesis in secondary mandibular condylar and primary costal cartilage of the rat were determined using a serum-free culture system. Somatomedin-C, multiplication-stimulating activity (MSA), epidermal growth factor (EGF) and insulin had a significant dose-dependent stimulating effect on proliferation in mandibular condylar cartilage. In costal cartilage, the same factors as well as parathyroid hormone (fragment 1-34), platelet-derived growth factor (PDGF) and high doses of human growth hormone (1 microgram/ml) significantly stimulated proliferation. Matrix synthesis in both cartilages could only be stimulated by high doses of insulin (100 micrograms/ml) and in costal cartilage also by parathyroid hormone. In this culture system fibroblast growth factor reduced proliferation and matrix production, while cartilage-derived factor had no marked effect on the growth processes in both cartilage types. Prominent differences between condylar and costal cartilage were demonstrated by the effects of parathyroid hormone and fetal calf serum. Although the effects on matrix synthesis were very moderate in the tissue culture system used, this study demonstrates that most factors conducive to growth in primary cartilage also stimulate growth in condylar cartilage only exposure to growth substances that interfere with the differentiation of prechondroblasts into chondroblasts, a process that is specific for appositionally growing secondary cartilage, may result in different responses between primary and secondary cartilage.


Synthesis of porous, nitrogen-doped adsorption/diffusion carbonaceous membranes for efficient CO2 separation.
A porous, nitrogen-doped carbonaceous free-standing membrane (TFMT-550) is prepared by a facile template-free method using letrozole as an intermediate to a triazole-functionalized-triazine framework, followed by carbonization. Such adsorption/diffusion membranes exhibit good separation performance of CO2 over N2 and surpassing the most recent Robeson upper bound. An exceptional ideal CO2 /N2 permselectivity of 47.5 was achieved with a good CO2 permeability of 2.40 × 10(-13) mol m m(-2) s(-1) Pa(-1) . The latter results arise from the presence of micropores, narrow distribution of small mesopores and from the strong dipole-quadrupole interactions between the large quadrupole moment of CO2 molecules and the polar sites associated with N groups (e.g., triazine units) within the framework.


Gene expression analysis of tumor spheroids reveals a role for suppressed DNA mismatch repair in multicellular resistance to alkylating agents.
Drug resistance is a major obstacle in the successful treatment of cancer. Thus, elucidation of the mechanisms responsible is a critical first step in trying to prevent or delay such manifestations of resistance. In this regard, three-dimensional multicellular tumor cell spheroids are intrinsically more resistant to virtually all anticancer cytotoxic drugs than conventional monolayer cultures. We have employed the EMT-6 subline PC5T, which forms highly compact spheroids, and differential display to identify candidate genes whose expression differs between monolayer and spheroids. Approximately 5,000 bands were analyzed, revealing 26 to be differentially expressed. Analysis of EMT-6 tumor variants selected in vivo for acquired resistance to alkylating agents identified eight genes whose expression correlated with drug resistance in tumor spheroids. Four genes (encoding Nop56, the NADH SDAP subunit, and two novel sequences) were found to be down-regulated in EMT-6 spheroids and four (encoding 2-oxoglutarate carrier protein, JTV-1, and two novel sequences) were up-regulated. Analysis of the DNA mismatch repair-associated PMS2 gene, which overlaps at the genomic level with the JTV-1 gene, revealed PMS2 mRNA to be down-regulated in tumor spheroids, which was confirmed at the protein level. Analysis of PMS2(-/-) mouse embryo fibroblasts confirmed a role for PMS2 in sensitivity to cisplatin, and DNA mismatch repair activity was found to be reduced in EMT-6 spheroids compared to monolayers. Dominant negative PMS2 transfection caused increased resistance to cisplatin in EMT-6 and CHO cells. Our results implicate reduced DNA mismatch repair as a determinant factor of reversible multicellular resistance of tumor cells to alkylating agents.


Catanionic and chain-packing effects on surfactant self-assembly in the ionic liquid ethylammonium nitrate.
Micelle formation, particularly the formation of compact, globular micelles in the high ionic strength environment of an ionic liquid, seems to be at odds with the principle of opposing forces and the concept of the surfactant packing parameter. Here we examine how interactions between polar head-groups, with solvent ions, and chain packing affect self-assembly structure in ionic liquids. The self-assembly of pure cationic and anionic surfactants, their catanionic mixtures, and the effect of the cosurfactant tetradecanol in the ionic liquid ethylammonium nitrate (EAN) is investigated by small-angle neutron scattering (SANS). The critical micelle concentrations of cationic surfactants are much higher and micelles much smaller in EAN than in water, whereas anionic micelles are less dramatically affected. Catanionic surfactant mixtures form small micelles in EAN at all compositions, unlike their counterparts in water which form vesicle dispersions or precipitates near 1:1 mol ratios. This contrasts with the behavior of cationic surfactants when mixed with double-chained analogs or alkanol cosurfactants, which induce micelle growth and shape transitions to rod-like and bilayer aggregates through chain packing effects similar to aqueous systems. This enables the aggregate morphology in the ionic liquid to be controlled through the composition of the surfactant mixtures.


Alfentanil dosage when inserting the classic laryngeal mask airway.
The purpose of this study was to determine an optimum dose of alfentanil, coadministered with 2.5 mg/kg propofol, when inserting a classic laryngeal mask airway. Seventy-five adult ethnic Chinese patients with an American Society of Anesthesiologists physiologic status classification I or II and requiring anesthesia for minor surgery with a laryngeal mask were recruited. They were randomly assigned to five dosage groups: placebo or 5, 10, 15, or 20 microg/kg. The study drug plus propofol were administered, and 90 s later, insertion conditions were assessed using a six-category score. The duration of apnea was recorded. A probit analysis was performed and used to estimate the ED50 and ED95 with 95% confidence intervals for each assessment. Twenty-five male and 50 female patients, aged 18-59 yr, were studied. The five groups were similar. Laryngeal mask insertion was successful in all but one alfentanil patient. Duration of apnea increased with increasing dosage of alfentanil to over 5 min (P < 0.001). Dose-responses could not be predicted for categories of resistance to mouth opening and to insertion. For the other four categories, swallowing, gagging, movement, and laryngospasm, ED50 and ED95 with confidence intervals for alfentanil could be determined. The optimum dose for alfentanil, when coadministered with 2.5 mg/kg propofol, was 10 microg/kg.


Clinical outcomes of linezolid and vancomycin in patients with nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus stratified by baseline renal function: a retrospective, cohort analysis.
The primary objective of this study is to assess whether baseline renal function impacts treatment outcomes of linezolid and vancomycin (with a dose-optimized regimen) for methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. We conducted a retrospective cohort analysis of data generated from a prospective, randomized, controlled clinical trial (NCT 00084266). The analysis included 405 patients with culture-proven MRSA pneumonia. Baseline renal function was stratified based on creatinine clearance. Clinical and microbiological success rates and presence of nephrotoxicity were assessed at the end of treatment (EOT) and end of study (EOS). Multivariate logistic regression analyses of baseline patient characteristics, including treatment, were performed to identify independent predictors of efficacy. Vancomycin concentrations were analyzed using a nonlinear mixed-effects modeling approach. The relationships between vancomycin exposures, pharmacokinetic-pharmacodynamic index (trough concentration, area under the curve over a 24-h interval [AUC0-24], and AUC0-24/MIC) and efficacy/nephrotoxicity were assessed in MRSA pneumonia patients using univariate logistic regression or Cox proportional hazards regression analysis approach. After controlling for use of vasoactive agents, choice of antibiotic therapy and bacteremia, baseline renal function was not correlated with clinical and microbiological successes in MRSA pneumonia at either end of treatment or at end of study for both treatment groups. No positive association was identified between vancomycin exposures and efficacy in these patients. Higher vancomycin exposures were correlated with an increased risk of nephrotoxicity (e.g., hazards ratio [95% confidence interval] for a 5 μg/ml increase in trough concentration: 1.42 [1.10, 1.82]). In non-dialysis patients, baseline renal function did not impact the differences in efficacy or nephrotoxicity with treatment of linezolid versus vancomycin in MRSA pneumonia.


DCC Is Required for the Development of Nociceptive Topognosis in Mice and Humans.
Avoidance of environmental dangers depends on nociceptive topognosis, or the ability to localize painful stimuli. This is proposed to rely on somatotopic maps arising from topographically organized point-to-point connections between the body surface and the CNS. To determine the role of topographic organization of spinal ascending projections in nociceptive topognosis, we generated a conditional knockout mouse lacking expression of the netrin1 receptor DCC in the spinal cord. These mice have an increased number of ipsilateral spinothalamic connections and exhibit aberrant activation of the somatosensory cortex in response to unilateral stimulation. Furthermore, spinal cord-specific Dcc knockout animals displayed mislocalized licking responses to formalin injection, indicating impaired topognosis. Similarly, humans with DCC mutations experience bilateral sensation evoked by unilateral somatosensory stimulation. Collectively, our results constitute functional evidence of the importance of topographic organization of spinofugal connections for nociceptive topognosis.


Emerging technologies for cervical cancer screening.
Cervical cancer remains a concern worldwide, and cervical cancer screening plays an important role in reducing the burden of this disease. Although cytology is still the main strategy for cervical cancer screening, it has gradually changed to human papillomavirus testing. The specificity of human papillomavirus testing is lower than that of cytology, which leads to an increased rate of colposcopy after positive results. To decrease colposcopic examinations, an efficient triage method is needed for human papillomavirus screening. New biomarkers have been developed and evaluated for primary screening and triage of abnormal cytology or human papillomavirus-positive results. Their sensitivity and specificity were estimated and compared with those of cytology. In the present study, the following new techniques were examined: p16/Ki67 dual staining, DNA methylation, micro-ribonucleic acid, chromosomal abnormalities, Claudins and DNA ploidy. Evaluation studies of p16/Ki67 dual staining and DNA methylation were more advanced than those of other options. When p16/Ki67 dual staining was used for triage for human papillomavirus testing, the sensitivity of 2 or greater cervical intraepithelial neoplasia (CIN2+) detection was higher than that of cytology without decreased specificity. Although there are several types of DNA methylation, sensitivity and specificity were moderate for detecting CIN2+. S5 classifier is a commercialized product that consists of viral methylation, and high sensitivity with decreased specificity has been reported. Considering its combination with self-sampling, DNA methylation is a highly anticipated technique along with human papillomavirus testing for the next generation of cervical cancer screening. However, the backgrounds for cervical cancer screening differ among countries and further study is needed to identify the best available method.


Cardiac Etiologies of Hydrops Fetalis.
Cardiac etiologies of hydrops fetalis have been a topic of concern due to challenging perinatal management. The common cardiac etiologies leading to hydrops fetalis include structural cardiac anomalies, cardiac dysrhythmias, cardiac tumors, cardiomyopathy and myocarditis. The mechanisms of cardiogenic hydrops fetalis may be: 1) elevation of atrial pressure and volume overload, 2) decrease of cardiac output, and 3) development of congestive heart failure. The diagnosis of hydrops fetalis was usually made at 19-36 gestational weeks, when ultrasound is a highly effective diagnostic method. Intrauterine interventions for certain congenital heart defects, maternal transplacental or direct fetal medications and fetal pacing placement for cardiac arrhythmias, and fetal or postnatal tumor resections are important progressions of etiologic treatment for hydrops fetalis. Treatment strategies for hydrops fetalis per se are usually ultrasound-guided pericardiocentesis and feto-amniotic shunting, whereas reaccumulation may require further interventions in utero or postnatally. Hydrops fetalis often carries a poor prognosis, and mortality remains high. Current developments in the management of hydrops fetalis should encourage physicians to attempt further fetal interventions.


Pediatric patellar dislocation.
Acute patellar dislocation affects approximately 1:1000 healthy children 9-15 years of age, and up to 50% are at risk for recurrent dislocations. In adults the condition is associated with long-term complications, such as osteoarthritis and impairment of knee function. However, literature describing the outcome in a pediatric population is sparse. The present review article evaluates the long-term effects on knee function and cartilage quality after traumatic patellar dislocation in childhood, and also to evaluate the reliability of two clinical tests of medio-lateral knee position, in healthy children.


A simple mass-spring model with roller feet can induce the ground reactions observed in human walking.
It has previously been shown that a bipedal model consisting of a point mass supported by spring limbs can be tuned to simulate periodic human walking. In this study, we incorporated roller feet into the spring-mass model and evaluated the effect of roller radius, impact angle, and limb stiffness on spatiotemporal gait characteristics, ground reactions, and center-of-pressure excursions. We also evaluated the potential of the improved model to predict speed-dependent changes in ground reaction forces and center-of-pressure excursions observed during normal human walking. We were able to find limit cycles that exhibited gait-like motion across a wide spectrum of model parameters. Incorporation of the roller foot (R=0.3 m) reduced the magnitude of peak ground reaction forces and allowed for forward center-of-pressure progression, making the model more consistent with human walking. At a fixed walking speed, increasing the limb impact angle reduced the cadence and prolonged stance duration. Increases in either limb stiffness or impact angle tended to result in more oscillatory vertical ground reactions. Simultaneous modulation of the limb impact angle and limb stiffness was needed to induce speed-related changes in ground reactions that were consistent with those measured during normal human walking, with better quantitative agreement achieved at slower speeds. We conclude that a simple mass-spring model with roller feet can well describe ground reaction forces, and hence center of mass motion, observed during normal human walking.


Human Lymph Node-Derived Fibroblastic and Double-Negative Reticular Cells Alter Their Chemokines and Cytokines Expression Profile Following Inflammatory Stimuli.
Lymph node (LN) is a secondary lymphoid organ with highly organized and compartmentalized structure. LNs harbor B, T, and other cells among fibroblastic reticular cells (FRCs). FRCs are characterized by both podoplanin (PDPN/gp38) expression and by the lack of CD31 expression. FRCs are involved in several immune response processes but mechanisms underlying their function are still under investigation. Double-negative cells (DNCs), another cell population within LNs, are even less understood. They do not express PDPN or CD31, their localization within the LN is unknown, and their phenotype and function remain to be elucidated. This study evaluates the gene expression and cytokines and chemokines profile of human LN-derived FRCs and DNCs during homeostasis and following inflammatory stimuli. Cytokines and chemokines secreted by human FRCs and DNCs partially diverged from those identified in murine models that used similar stimulation. Cytokine and chemokine secretion and their receptors expression levels differed between stimulated DNCs and FRCs, with FRCs expressing a broader range of chemokines. Additionally, dendritic cells demonstrated increased migration toward FRCs, possibly due to chemokine-induced chemotaxis since migration was significantly decreased upon neutralization of secreted CCL2 and CCL20. Our study contributes to the understanding of the biology and functions of FRCs and DNCs and, accordingly, of the mechanisms involving them in immune cells activation and migration.


Volatilization of elemental mercury from fresh blast furnace sludge mixed with basic oxygen furnace sludge under different temperatures.
Blast furnace sludge (BFS) is a waste with elevated mercury (Hg) content due to enrichment during the production process of pig iron. To investigate the volatilization potential of Hg, fresh samples of BFS mixed with basic oxygen furnace sludge (BOFS; a residue of gas purification from steel making, processed simultaneously in the cleaning devices of BFS and hence mixed with BFS) were studied in sealed column experiments at different temperatures (15, 25, and 35 °C) for four weeks (total Hg: 0.178 mg kg(-1)). The systems were regularly flushed with ambient air (every 24 h for the first 100 h, followed by every 72 h) for 20 min at a flow rate of 0.25 ± 0.03 L min(-1) and elemental Hg vapor was trapped on gold coated sand. Volatilization was 0.276 ± 0.065 ng (x m: 0.284 ng) at 15 °C, 5.55 ± 2.83 ng (x m: 5.09 ng) at 25 °C, and 2.37 ± 0.514 ng (x m: 2.34 ng) at 35 °C. Surprisingly, Hg fluxes were lower at 35 than 25 °C. For all temperature variants, an elevated Hg flux was observed within the first 100 h followed by a decrease of volatilization thereafter. However, the background level of ambient air was not achieved at the end of the experiments indicating that BFS mixed with BOFS still possessed Hg volatilization potential.


Genome-Wide Association Study Reveals the Genetic Basis of Stalk Cell Wall Components in Maize.
Lignin, cellulose and hemicellulose are the three main components of the plant cell wall and can impact stalk quality by affecting cell wall structure and strength. In this study, we evaluated the lignin (LIG), cellulose (CEL) and hemicellulose (HC) contents in maize using an association mapping panel that included 368 inbred lines in seven environments. A genome-wide association study using approximately 0.56 million SNPs with a minor allele frequency of 0.05 identified 22, 18 and 24 loci significantly associated with LIG, CEL and HC at P < 1.0×10-4, respectively. The allelic variation of each significant association contributed 4 to 7% of the phenotypic variation. Candidate genes identified by GWAS mainly encode enzymes involved in cell wall metabolism, transcription factors, protein kinase and protein related to other biological processes. Among the association signals, six candidate genes had pleiotropic effects on lignin and cellulose content. These results provide valuable information for better understanding the genetic basis of stalk cell wall components in maize.


Change of the donor substrate specificity of Clostridium difficile toxin B by site-directed mutagenesis.
The large cytotoxins of Clostridia species glycosylate and thereby inactivate small GTPases of the Rho family. Clostridium difficile toxins A and B and Clostridium sordellii lethal toxin use UDP-glucose as the donor for glucosylation of Rho/Ras GTPases. In contrast, alpha-toxin from Clostridium novyi N-acetylglucosaminylates Rho GTPases by using UDP-N-acetylglucosamine as a donor substrate. Based on the crystal structure of C. difficile toxin B, we studied the sugar donor specificity of the toxins by site-directed mutagenesis. The changing of Ile-383 and Gln-385 in toxin B to serine and alanine, respectively, largely increased the acceptance of UDP-N-acetylglucosamine as a sugar donor for modification of RhoA. The K(m) value was reduced from 960 to 26 mum for the double mutant. Accordingly, the potential of the double mutant of toxin B to hydrolyze UDP-N-acetylglucosamine was higher than that for UDP-glucose. The changing of Ile-383 and Gln-385 in the lethal toxin of C. sordellii allowed modification of Ras in the presence of UDP-N-acetyl-glucosamine and reduced the acceptance of UDP-glucose as a donor for glycosylation. Vice versa, the changing of the equivalent residues in C. novyi alpha-toxin from Ser-385 and Ala-387 to isoleucine and glutamine, respectively, reversed the donor specificity of the toxin from UDP-N-acetylglucosamine to UDP-glucose. These data demonstrate that two amino acid residues are crucial for the co-substrate specificity of clostridial glycosylating toxins.


Where has all the chlamydia come from? The clinical impact of the introduction of an improved chlamydia test.
At a time of increasing demands on genitourinary (GU) medicine clinics, the introduction of a new nucleic acid test to a GU medicine clinic has the potential to increase the workload due to increased numbers of patients being identified with chlamydia, and a consequent increase in partner notification. In one clinic setting, we found a doubling in the rates of chlamydial infection following the introduction of a new test, but a concomitant reduction in the rates of non-specific genital infection. The improved specificity of the test has made counselling of patients with chlamydia and non-specific infection much easier. An audit has shown that contact-tracing outcomes are significantly better in patients who are diagnosed with chlamydia.


The Japanese American wartime incarceration: Examining the scope of racial trauma.
Ten weeks after the 1941 Japanese military attack on Pearl Harbor, Hawaii, the U.S. government authorized the removal of more than 110,000 Japanese American men, women, and children from their homes in Western portions of the country to incarceration camps in desolate areas of the United States. The mass incarceration was portrayed as necessary to protect the country from potential acts of espionage or sabotage that might be committed by someone of Japanese ancestry. However, an extensive government review initiated in 1980 found no evidence of military necessity to support the removal decision and concluded that the incarceration was a grave injustice fueled by racism and war hysteria. The Japanese American wartime experience represents a powerful case example of race-based historical trauma. This article describes the consequences of the incarceration for Japanese Americans during and after their unjust imprisonment, their coping responses and healing strategies, as well as the impacts of receiving governmental redress more than four decades after the war's end. Examination of this specific event provides a perspective for understanding the long-term, radiating effects of racial trauma and the process of healing, over a broad arc of time and across social contexts. Current relevance of the Japanese American incarceration and implications for the field of psychology are discussed. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Knockdown of hMex-3A by small RNA interference suppresses cell proliferation and migration in human gastric cancer cells.
RNA-binding proteins (RBPs) play essential roles in RNA metabolism, regulating RNA splicing, transport, surveillance, decay and translation. The aberrant expression of RBPs leads to gene expression alteration and frequently causes various diseases, such as cancer. In this study, we are the first to provide evidence that hMex-3A, a RBP that belongs to the human Mex-3 family with two K-homology RNA-binding domains, is involved in the regulation of tumorigenesis. We show that the silencing of hMex-3A by small interference RNA effectively inhibits cell proliferation in SNU-16 and AGS gastric cancer cells. Flow cytometry analysis confirmed this effect on SNU-16 cell growth and indicated that hMex-3A may function in the G1/M phase. Notably, hMex-3A knockdown also reduced the colony formation ability of SNU-16 and AGS cells in soft agar, implying that hMex-3A is required for cell transformation. Furthermore, the hMex-3A knockdown markedly affected the migratory ability of BCG-823 cells by transwell chamber and wound healing assays. Clinical relevance analysis using 22 paired gastric cancer specimens by quantitative real-time PCR showed that hMex-3A was significantly upregulated (63.6%) in cancer tissues compared with matched adjacent non-cancerous tissues. Taken together, these results suggest that hMex-3A functions as an oncogene candidate in the development and metastasis of gastric cancer; thus it may serve as a potential target for the therapy of tumors.


Unraveling the mystery of pain in chronic pancreatitis.
Over 95% of patients with chronic pancreatitis have intractable abdominal pain. The etiology of the pain remains unclear and is considered multifocal. Treating pain associated with chronic pancreatitis requires a comprehensive approach. This care model encompasses interventional, medical, and adjuvant therapies for both pain and symptom management. Maximizing pain and symptom management in patients with chronic pancreatitis results in timely discharges from the hospital, fewer readmissions, and overall decrease in emergency department visitations. Proper assessment and management of pain and symptoms in patients with chronic pancreatitis improves overall quality of life.


Evaluation of the CASPAR alcohol education curriculum.
The CASPAR education-prevention program was initiated when experimental results indicated that a 5-hr alcohol education curriculum at a Catholic high school was able to reduce frequent intoxication among teenagers. Attempts to institutionalize such a program in the public schools shows that (1) alcohol education can generate widespread community and school support; (2) workshops can successfully train teachers to adopt a decision-making approach, though close supervision is needed to ensure that this approach is adhered to in classroom teaching; (3) the CASPAR model of alcohol education produces classroom situations conducive to many children feeling free to express alcohol-related concerns; (4) trained teachers can serve as intermediaries between students with alcohol-related concerns and community resources, in particular those resources that are designed to help children from families with alcoholism; (5) the CASPAR curriculum, implemented by trained teachers, produces statistically significant knowledge and attitude gains, whereas alternate programs such as a special-events approach produce smaller knowledge gains and little attitude change; and (6) to a considerable extent, knowledge and attitude gains persist over time, although retention is greater on knowledge items and among older students. The results suggest that there may be a behavioral impact of instruction in the form of reduced alcohol misuse among teenagers, although if there is, it requires intensive and repeated exposure and can be demonstrated in these data only among younger students while they remain in junior high school. Although such results may be viewed as less supportive than the original experiment with which this work began, they do suggest that alcohol education remains an effective prevention strategy.


Mentoring serial and high-risk perpetrators of intimate partner violence in the community: Engagement and initiating change.
Mentoring has typically been used with young offenders. A pilot-mentoring project has been introduced in the UK for high-risk intimate partner violence (IPV) offenders. The aim of the study was to evaluate how serial and high-risk IPV men engaged with mentoring and how change was initiated for this population. Interviews were conducted with two mentors, six mentees and four support workers, and file notes for 16 mentees were examined. Thematic analysis was employed to analyse the data. The global theme, tools and techniques that facilitate engagement comprised two organising themes, building relationships and tenacity of the mentor, which explained how engagement was initiated and driven. Catalysts to initiate change with its two organising themes, hooks and focus on the future, captured factors that act as potential turning points or triggers for the mentees to address their use of IPV and start the process of change. Mentoring is an innovative and alternative approach for engaging intervention-resistant serial and high-risk IPV perpetrators, enabling them to identify their need to change and laying down the foundation that could facilitate this change.


Efficient utilization of ectoine by halophilic Brevibacterium species and Escherichia coli subjected to osmotic downshock.
Halophilic and non-halophilic bacteria subjected to osmotic downshock, from 0.7 M NaCl to deionized water, were examined for their survival, with the uptake and utilization of the cyclic amino acid ectoine, one of the representative compatible solutes, being taken into account. The uptake of ectoine added externally and survival of the cells were monitored as a function of incubation time in the presence and absence of NaCl. The halophilic Brevibacterium sp. JCM 6894 and B. epidermidis JCM 2593 actively accumulated ectoine regardless of the presence of NaCl, which led to cell survival. Brevibacterium casei JCM 2594 belonging to the same Brevibacterium species, however, revealed Na+-dependence of its uptake activity of ectoine. Non-halophilic Escherichia coli K-12 did not accumulate ectoine, and thereby this strain failed to survive irrespective of whether NaCl was present. The physiological meanings of the downshock procedure are discussed in connection with the uptake and the subsequent utilization of ectoine.


Probing BoNT/A protease exosites: implications for inhibitor design and light chain longevity.
Botulinum neurotoxin serotype A (BoNT/A) is one of the most lethal toxins known. Its extreme toxicity is due to its light chain (LC), a zinc protease that cleaves SNAP-25, a synaptosome-associated protein, leading to the inhibition of neuronal activity. Studies on BoNT/A LC have revealed that two regions, termed exosites, can play an important role in BoNT catalytic activity. A clear understanding of how these exosites influence neurotoxin catalytic activity would provide a critical framework for deciphering the mechanism of SNAP-25 cleavage and the design of inhibitors. Herein, based on the crystallographic structure of BoNT/A LC complexed with its substrate, we designed an α-exosite binding probe. Experiments with this unique probe demonstrated that α-exosite binding enhanced both catalytic activity and stability of the LC. These data help delineate why α-exosite binding is needed for SNAP-25 cleavage and also provide new insights into the extended lifetime observed for BoNT/A LC in vivo.


Effects of ATP, its related nucleotides and VIP on the inhibitory potentials in the smooth muscle cells of the guinea-pig duodenum.
Non-adrenergic inhibitory potentials (i.p.'s) were recorded from the smooth muscle cells of the guinea-pig duodenum following field stimulation. ATP, ADP and AMP increased the membrane potential of the cell and decreased the amplitude and the rate of hyperpolarization of the i.p. The amplitudes of the maximum hyperpolarization due to a repeated stimulation and the post-stimulus depolarization were reduced by ATP and AMP. Methylxanthine could not inhibit the i.p. while apamin reversibly decreased the amplitudes of the i.p. and the post-stimulus depolarization. The latency and the time to peak were prolonged by apamin. Biphasic effect of quinidine on the i.p. was obtained. The amplitude and the rate of hyperpolarization of the i.p. were decreased at 10-4 g/ml of quinidine. The amplitudes of the maximum hyperpolarization by repetitive stimulation and the post-stimulus depolarization were decreased by quinidine. The membrane potential of the cell was not affected by VIP. The amplitude and the other parameters of the i.p. were not changed in the used concentration of VIP. Trypsin reduced the membrane potential of the cell but not changed the parameters of the i.p. The membrane was slightly depolarized by the treatment with papain while no significant changes on the i.p. were observed in papain. The obtained results suggest that ATP, its related substances and VIP do not contribute to the non-adrenergic inhibitory neurotransmission.


Strained alkenes in natural product synthesis.
Strained molecules continue to challenge the ingenuity of chemists as their high-energy bonds serve as fuel for the promotion of complex synthetic transformations. Developments in this area have resulted in the recent emergence of strained alkenes as intermediates in natural product synthesis. This Minireview highlights these recent advances along with current developments toward understanding the unique reactivity of strained alkenes.


Therapeutic implications of converting-enzyme inhibitors in renal disease.
Micropuncture and morphological studies were performed in three protocols assessing the renal hemodynamic and structural effects of angiotensin I-converting enzyme inhibitors (CEIs) in the progression of glomerular injury. In protocol I, rats were subjected to 5/6 renal ablation and received no therapy, enalapril (CEI), or triple-drug therapy (TRX) for 12 weeks. Control of systemic and glomerular hypertension with CEI resulted in prevention of glomerular capillary hypertension and protection against glomerular injury. Despite equivalent control of systemic BP, failure of TRX to control glomerular hypertension was associated with no protection against eventual proteinuria and glomerular sclerosis, values for these indexes being as abnormal as in rats receiving no therapy. In protocol II, rats were again subjected to 5/6 renal ablation and followed for 18 weeks. Early institution of CEI soon after ablation again prevented systemic and glomerular hypertension and largely limited glomerular injury. In a third group, enalapril therapy was delayed for 8 weeks after ablation until hypertension and proteinuria were established. Late institution of CEI resulted in prompt reduction in systemic and glomerular capillary hypertension and stabilization of glomerular disease. In protocol III, CEI was administered to normotensive, moderately hyperglycemic diabetic rats. A modest, 20-mm Hg reduction in systemic arterial pressure was associated with the normalization of glomerular capillary pressure and a striking reduction in the development of albuminuria and glomerular injury. These studies suggest that CEI effectively prevent glomerular capillary hypertension and thereby afford protection against glomerular injury in diverse models of progressive renal disease.


Assembly, maturation and three-dimensional helical structure of the teratogenic rubella virus.
Viral infections during pregnancy are a significant cause of infant morbidity and mortality. Of these, rubella virus infection is a well-substantiated example that leads to miscarriages or severe fetal defects. However, structural information about the rubella virus has been lacking due to the pleomorphic nature of the virions. Here we report a helical structure of rubella virions using cryo-electron tomography. Sub-tomogram averaging of the surface spikes established the relative positions of the viral glycoproteins, which differed from the earlier icosahedral models of the virus. Tomographic analyses of in vitro assembled nucleocapsids and virions provide a template for viral assembly. Comparisons of immature and mature virions show large rearrangements in the glycoproteins that may be essential for forming the infectious virions. These results present the first known example of a helical membrane-enveloped virus, while also providing a structural basis for its assembly and maturation pathway.


Long-term Developmental Trends of Pediatric Mitochondrial Diseases: The Five Stages of Developmental Decline.
Mitochondrial diseases (MDs) are a heterogeneous group of progressive multisystem disorders caused by impaired mitochondrial function. This study aimed to evaluate the clinical course and long-term development of 53 pediatric patients with MDs. Developmental function was evaluated at nine time points (two pre-diagnosis, one at diagnosis, and six post-diagnosis), with the developmental quotient (DQ) from the Korean infant and child development test (KICDT) assessing a child's developmental age (rather than chronological age). Additionally, disease-related clinical variables were reviewed, and clinical progress was determined through observation. Subgroup analyses by epilepsy severity, syndromic diagnosis, diffuse brain atrophy, and clinical rating were performed. The pre- and post-diagnosis results were compared by the paired t-test and Bonferroni correction. The pre-diagnostic, diagnostic, and post-diagnostic evaluations were compared using repeated measures ANOVA. Patients with diffuse brain atrophy at the first pre-diagnostic and second post-diagnostic evaluations showed lower DQs. Compared with patients with a mildly or severely deteriorating clinical course, those with an improving or static clinical course presented higher DQs at the pre-diagnostic and diagnostic evaluations. The age at onset of the first symptom correlated positively with the DQ post-diagnosis. Follow-up revealed consistent patterns of significant developmental deterioration during the lead time to diagnosis, with no significant decline post-diagnosis. The DQ is a feasible predictor and a measure of long-term functional development in children with MD. Early initiation of treatment may minimize developmental regression.


Minimal model for synchronization induced by hydrodynamic interactions.
Motivated by the observed coordination of nearby beating cilia, we use a scale model experiment to show that hydrodynamic interactions can cause synchronization between rotating paddles driven at constant torque in a very viscous fluid. Synchronization is only observed when the shafts supporting the paddles have some flexibility. The phase difference in the synchronized state depends on the symmetry of the paddles. We use the method of regularized Stokeslets to model the paddles and find excellent agreement with the experimental observations. We also use a simple analytic theory based on far-field approximations to derive scaling laws for the synchronization time as a function of paddle separation.


Skin grafts in intraoral reconstruction. A new stenting method.
The results of skin graft reconstruction in intraoral cancer in 65 consecutive cases were uniformly good. There were only 11 wound complications and all resolved spontaneously without additional surgery. Skin grafts were used successfully in conjunction with coronal resections of the mandible, incontinuity modified neck dissections, and composite resections. Postoperative radiation therapy had no ill effects on the grafts or oral hygiene. A new stenting method with a dental tissue conditioner was employed. When used to immobilize intraoral skin grafts, it improved oral hygiene and patient deglutition, thereby hastening rehabilitation. The success of grafts performed with the new stent was equal to (if not better than) the success of grafts performed with the traditional stent.


Comparison of Two Radiotherapy Regimens for Metastatic Spinal Cord Compression: Subgroup Analyses from a Randomized Trial.
According to our randomized trial, 5×4Gy was comparable to 10×3Gy for metastatic spinal cord compression. Since it remained unclear whether findings applied to poor and intermediate prognoses patients, subgroup analyses were performed. In patients with poor prognoses, 58 received 5×4Gy, 53 received 10×3Gy. In intermediate-prognoses patients, numbers were 43 and 49. In patients with poor prognoses, 1-month overall response (OR) was 85% after 5×4Gy and 10×3Gy (p=0.99), improvement 38% vs. 42%, ambulatory status 60% vs. 64% (p=0.83), 6-month local progression-free survival (LPFS) 75% vs. 69% (p=0.74) and 6-month overall survival (OS) 26% vs. 19% (p=0.43). In patients with intermediate prognoses, 1-month OR was 89% after 5×4Gy and 93% after 10×3Gy (p=0.85), improvement 39% vs. 45%, ambulatory status 84% vs. 82% (p=0.90), 6-month LPFS 79% vs. 92% (p=0.17) and 6-months OS 65% vs. 58% (p=0.65). 5×4Gy was not significantly inferior to 10x3Gy in both subgroups.


Calculation of Haem Iron Intake and Its Role in the Development of Iron Deficiency in Young Women from the Australian Longitudinal Study on Women's Health.
Total iron intake is not strongly associated with iron stores, but haem iron intake may be more predictive. Haem iron is not available in most nutrient databases, so experimentally determined haem contents were applied to an Australian Food Frequency Questionnaire (FFQ) to estimate haem iron intake in a representative sample of young women (25-30 years). The association between dietary haem iron intakes and incident self-reported diagnosed iron deficiency over six years of follow-up was examined. Haem iron contents for Australian red meats, fish, and poultry were applied to haem-containing foods in the Dietary Questionnaire for Epidemiological Studies V2 (DQESv2) FFQ. Haem iron intakes were calculated for 9076 women from the Australian Longitudinal Study on Women's Health (ALSWH) using the DQESv2 dietary data from 2003. Logistic regression was used to examine the association between haem iron intake (2003) and the incidence of iron deficiency in 2006 and 2009. Multiple logistic regression showed baseline haem iron intake was a statistically significant predictor of iron deficiency in 2006 (Odds Ratio (OR): 0.91; 95% Confidence Interval (CI): 0.84-0.99; p-value: 0.020) and 2009 (OR: 0.89; 95% CI: 0.82-0.99; p-value: 0.007). Using the energy-adjusted haem intake made little difference to the associations. Higher haem iron intake is associated with reduced odds of iron deficiency developing in young adult Australian women.


Dual-view transport of intensity phase imaging flow cytometry.
In this work, we design multi-parameter phase imaging flow cytometry based on dual-view transport of intensity (MPFC), which integrates phase imaging and microfluidics to a microscope, to obtain single-shot quantitative phase imaging on cells flowing in the microfluidic channel. The MPFC system has been proven with simple configuration, accurate phase retrieval, high imaging contrast, and real-time imaging and has been successfully employed not only in imaging, recognizing, and analyzing the flowing cells even with high-flowing velocities but also in tracking cell motilities, including rotation and binary rotation. Current results suggest that our proposed MPFC provides an effective tool for imaging and analyzing cells in microfluidics and can be potentially used in both fundamental and clinical studies.


Image-based reporting for bronchoscopy.
Bronchoscopy is often performed for staging lung cancer. The recent development of multidetector computed tomography (MDCT) scanners and ultrathin bronchoscopes now enable the bronchoscopic biopsy and treatment of peripheral diagnostic regions of interest (ROIs). Because these ROIs are often located several generations within the airway tree, careful planning and interpretation of the bronchoscopic route is required prior to a procedure. The current practice for planning bronchoscopic procedures, however, is difficult, error prone, and time consuming. To alleviate these issues, we propose a method for producing and previewing reports for bronchoscopic procedures using patient-specific MDCT chest scans. The reports provide quantitative data about the bronchoscopic routes and both static and dynamic previews of the proper airway route. The previews consist of virtual bronchoscopic endoluminal renderings along the route and three-dimensional cues for a final biopsy site. The reports require little storage space and computational resources, enabling physicians to view the reports on a portable tablet PC. To evaluate the efficacy of the reporting system, we have generated reports for 22 patients in a human lung cancer patient pilot study. For 17 of these patients, we used the reports in conjunction with live image-based bronchoscopic guidance to direct physicians to central chest and peripheral ROIs for subsequent diagnostic evaluation. Our experience shows that the tool enabled useful procedure preview and an effective means for planning strategy prior to a live bronchoscopy.


Effect of conditions being present at time of surgery (PATOS) on outcomes in liver surgery.
Information about condition(s) being present at time of surgery (PATOS) in the American College of Surgeons (ASC) National Surgical Quality Improvement Program (NSQIP) database can influence the postoperative complication rates after liver surgeries. Here, we compare the postoperative complication rates with and without taking condition(s) being PATOS into account. We retrospectively reviewed the ACS NSQIP Participant User Files (PUFs) from 2015 through 2019. We analyzed rates of eight different postoperative complications: superficial surgical site infection (SSI), deep SSI, organ space SSI, pneumonia, urinary tract infection, ventilator, sepsis, and septic shock. In addition, we calculated the percent change in event rates after taking into account whether a condition is PATOS. Of the 22,463 patients in the ACS NSQIP PUFs for liver surgery, 334 (1.49%) had one or more conditions PATOS. The percentages of patients with PATOS events ranged from 2.03% for superficial SSI to 14.74% for sepsis. For all complications, event rates declined when taking condition(s) PATOS into account. From 2015 through 2019, the observed-to-expected ratios for most complications remained unchanged. Whether a condition is PATOS is important in reporting postoperative complication rates for patients undergoing liver surgery. When taking whether a condition is PATOS into account, we demonstrated an overall decrease in event rates across all eight postoperative complications.


Time preference and its relationship with age, health, and survival probability.
Although theories from economics and evolutionary biology predict that one's age, health, and survival probability should be associated with one's subjective discount rate (SDR), few studies have empirically tested for these links. Our study analyzes in detail how the SDR is related to age, health, and survival probability, by surveying a sample of individuals in townships around Durban, South Africa. In contrast to previous studies, we find that age is not significantly related to the SDR, but both physical health and survival expectations have a U-shaped relationship with the SDR. Individuals in very poor health have high discount rates, and those in very good health also have high discount rates. Similarly, those with expected survival probability on the extremes have high discount rates. Therefore, health and survival probability, and not age, seem to be predictors of one's SDR in an area of the world with high morbidity and mortality.


The moral deliberation pathway in veterinary practice: a qualitative study.
Veterinarians may face various ethical decisions and potential moral conflicts in clinical practice. The ethical decision-making process often leads to a satisfying resolution. However, when such a process is accompanied by a perceived inability to act according to a person's values, it can lead to psychological distress that characterises moral distress. Theoretical models in professions such as nursing attempt to explain the evolution of moral conflict into moral distress. In veterinary professionals, a model has been proposed to explain this pathway (the moral deliberation pathway). However, empirical data are still lacking on whether veterinary clinicians experience a moral deliberation pathway as hypothesised. Using thematic analysis, this qualitative study investigates veterinary clinicians' experiences with moral distress and aims to explain the moral deliberation pathway in these veterinarians. The results suggest that veterinarians' experiences with moral distress follow a deliberation process that can be explained by the proposed moral deliberation pathway. Experiencing a moral conflict leads to moral stress, then either to moral distress or resolution into moral comfort. Self-selection of participants and possible recollection bias may have biased the findings. The empirical data provided by this study can inform future research and intervention strategies to identify, measure and manage moral distress in the veterinary context.


Genome-wide dissection and expression profiling of unique glyoxalase III genes in soybean reveal the differential pattern of transcriptional regulation.
Reactive carbonyl species, such as methylglyoxal and glyoxal are very toxic in nature and can inactivate various cellular macromolecules such as DNA, RNA, and protein by forming advanced glycation end products. Conventional glyoxalase pathway with two enzymes- glyoxalase I and glyoxalase II, detoxify MG into D-lactate with the help of reduced glutathione. However, DJ-1/PfpI domain(s) containing DJ-1/ Hsp31 proteins do the same in a single step, and thus termed as "glyoxalase III". A comprehensive genome-wide analysis of soybean identified eleven putative glyoxalase III proteins with DJ-1/PfpI domain encoded by seven genes. Most of these proteins are predicted to be mitochondria and chloroplast localized. In spite of similar function, a differential evolution pattern was observed between Hsp31 and DJ-1 proteins. Expression of GmDJ-1A, GmDJ-1B, and GmDJ-1D2 transcripts was found to be constitutive in different tissues and developmental stages. Transcript profiling revealed the strong substrate-specific upregulation of GmDJ-1 genes in response to exogenous methylglyoxal exposure. Out of seven genes, GmDJ-1D1 and GmDJ-1D2 showed maximum upregulation against salinity, dehydration, and oxidative stresses. Moreover, GmDJ-1D2 showed functional glyoxalase III enzyme activity by utilizing MG as a substrate. Overall, this study identifies some novel tissue-specific and abiotic stress-responsive GmDJ-1 genes that could be investigated further.


When is a sentinel node biopsy indicated for patients with primary melanoma? An update of the 'Australian guidelines for the management of cutaneous melanoma'.
A sentinel lymph node biopsy is a surgical staging procedure performed for patients with primary cutaneous melanoma who are clinically lymph-node negative to determine whether there is low volume nodal metastasis in the draining lymph node field. A systematic review was recently performed to update the Australian clinical practice guidelines for the diagnosis and management of melanoma, addressing the question, 'When is a sentinel lymph node biopsy indicated?' This article discusses the findings of the systematic review and the evidence base for the updated guidelines.


Synaptic and spiking dynamics underlying reward reversal in the orbitofrontal cortex.
Cognitive and emotional flexibility involve a coordinated interaction between working memory, attention, reward expectations, and the evaluation of rewards and punishers so that behaviour can be changed if necessary. We describe a model at the integrate-and-fire neuronal level of the synaptic and spiking mechanisms which can hold an expectation of a reward rule in working memory, and can reverse the reward rule if expected rewards are not obtained. An example of a reward rule is that stimulus 1 is currently associated with reward, and stimulus 2 with punishment. The attractor-based reward rule working memory incorporates a spike-frequency synaptic adaptation mechanism which supports the neural switching between rules by being shut down by a general inhibitory input produced by punishment, so that when the attractor starts up again is in the opposite state. The mechanism can implement one-trial reward reversal, which is a property of orbitofrontal cortex neurons. We show how this reward rule input can operate in a biased competition way to influence which one of two stimuli is currently associated with reward and which with punishment, and to map the stimuli correctly to the reward or punishment representations, providing a basis for action selection required to obtain the reinforcer.


[Management, prevention and control of anaemia secondary to iron deficiency].
Anemia secondary to iron deficiency is the most frequent anaemia in our environment, the first cause of consultation in Haematology and the most common nutritional problem. It is characterized by a diminution or absence of iron deposits. The ultimate test that confirms the diagnosis of anaemia secondary to iron deficiency is a low serum level of ferritin, which indicates iron depletion. Other parameters do not allow to distinguish iron deficiency anaemia from other chronic derangements. Diet is of utmost importance in anaemia. There is not a single food product with sufficient concentration of iron capable of restoring iron deficiency situations. Therefore, treatment of iron deficiency must be made orally with iron preparates, mainly in the form of iron sulphate in order to guarantee a better absorption. The initial recommended doses are 150-200 mg of elemental iron per day split in three ingestions (in children 3-5 mg/Kg/day).


Postnatal intermittent hypoxia alters baroreflex function in adult rats.
Chronic perinatal intermittent hypoxia (IH) could have long-term cardiovascular effects by altering baroreflex function. To examine this hypothesis, we exposed rats (n = 6/group) for postnatal days 1-30 or prenatal embryonic days 5-21 to IH (8% ambient O2 for 90 s after 90 s of 21% of O2, 12 h/day) or to normoxia (control). Baroreflex sensitivity (BRS) and cardiac chronotropic responses were examined in anesthetized animals 3.5-5 mo later by infusing phenylephrine or sodium nitroprusside (6-12 microg/min iv, 1-2 min) during normoxia and after 18 min of acute IH (IHA). In controls after IHA, baroreflex gain was 42% (P < 0.05) less than during normoxia. BRS in the postnatal IH group during normoxia was approximately 50% less than in control rats and similar to controls after IHA. The heart rate response to phenylephrine in the IH group was also less than in controls (P < 0.05) and was not changed by IHA. BRS and heart rate responses in the prenatal IH group were similar to the normoxic control group. Vagal efferent projections to atrial ganglia neurons in rats after postnatal IH (n = 4) were examined by injecting tracer into the left nucleus ambiguous. After 35 days of postnatal IH, basket ending density was reduced by 17% (P < 0.001) and vagal axon varicose contacts by 56% (P < 0.001) compared with controls. We conclude that reduction of vagal efferent projections in cardiac ganglia could be a cause of long-term modifications in baroreflex function.


Sustained inhibition of HIV-1 replication by conditional expression of the E. coli-derived endoribonuclease MazF in CD4+ T cells.
Gene therapy using a Tat-dependent expression system of MazF, an ACA nucleotide sequence-specific endoribonuclease derived from Escherichia coli, in a retroviral vector appears to be an alternative approach to the treatment of human immunodeficiency virus type 1 (HIV-1) infection. MazF can cleave HIV-1 RNA, since it has more than 240 ACA sequences. Significant inhibition of viral replication, irrespective of HIV-1 strains, was observed in CD4(+) T cells that had been transduced with the MazF-expressing retroviral vector (MazF-T cells). The growth and viability of MazF-T cells were not affected by HIV-1 infection. Interestingly, the infectivity of HIV-1 produced from MazF-T cells was found to be lower than that from control CD4(+) T cells. A long-term culture experiment with HIV-1-infected cells revealed that viral replication was always lower in MazF-T cells than in CD4(+) T cells transduced with or without a control vector for more than 200 days. MazF was expressed and mainly localized in the cytoplasm of the infected cells. Unlike in CD4(+) T cells, the expression level of Tat gradually decreased rather than increased in MazF-T cells after HIV-1 infection. As a consequence, the expression level of MazF appeared to be well regulated and sustained during HIV-1 infection in MazF-T cells. Furthermore, the levels of cellular mRNA were not affected by HIV-1 infection. Thus, the Tat-dependent MazF expression system has great potential for inhibition of HIV-1 replication in vivo without apparent toxicity and may be able to avoid the emergence of resistant strains.


Structural plasticity in mesencephalic dopaminergic neurons produced by drugs of abuse: critical role of BDNF and dopamine.
Mesencephalic dopaminergic neurons were suggested to be a critical physiopathology substrate for addiction disorders. Among neuroadaptive processes to addictive drugs, structural plasticity has attracted attention. While structural plasticity occurs at both pre- and post-synaptic levels in the mesolimbic dopaminergic system, the present review focuses only on dopaminergic neurons. Exposures to addictive drugs determine two opposite structural responses, hypothrophic plasticity produced by opioids and cannabinoids (in particular during the early withdrawal phase) and hypertrophic plasticity, mostly driven by psychostimulants and nicotine. In vitro and in vivo studies identified BDNF and extracellular dopamine as two critical factors in determining structural plasticity, the two molecules sharing similar intracellular pathways involved in cell soma and dendrite growth, the MEK-ERK1/2 and the PI3K-Akt-mTOR, via preferential activation of TrkB and dopamine D3 receptors, respectively. At present information regarding specific structural changes associated to the various stages of the addiction cycle is incomplete. Encouraging neuroimaging data in humans indirectly support the preclinical evidence of hypotrophic and hypertrophic effects, suggesting a possible differential engagement of dopamine neurons in parallel and partially converging circuits controlling motivation, stress, and emotions.


HIV-induced abnormalities in myelopoiesis and their recovery following antiretroviral therapy.
HIV-1 infection is associated with hematologic abnormalities including defective myelopoiesis. Most studies of myelopoiesis during HIV-1 infection were performed using unfractionated bone marrow-derived mononuclear cells, thus resulting in significant inter-individual variability in the numbers of cultured precursors. Here we evaluated the myelopoietic potential of circulating CD34+ progenitors by conducting a longitudinal analysis of antiretroviral therapy (ART)-induced changes of colony forming units-granulocyte and monocyte (CFU-GM) growth. Twelve HIV-infected individuals were studied longitudinally before and after initiation of ART (i.e. at a time when plasma HIV-RNA levels had become undetectable); thirty-one HIV-uninfected healthy individuals were enrolled as controls. Peripheral blood-derived CD34+ progenitors were purified by immunomagnetic sorting, and cultured in methylcellulose-based medium containing stem cell factor, granulocyte-monocyte colony-stimulating factor and interleukin-3. ART-induced changes in the proportion of CD8+ T cells expressing surface HLA-DR were also evaluated. We found that CFU-GM levels were increased in untreated HIV-infected individuals when compared to uninfected controls but declined significantly following ART, in parallel with the decline of HIV-RNA levels in plasma and with the down-regulation of HLA-DR expression on CD8+ T cells. These findings suggest that, in untreated HIV-infected individuals, chronic inflammation and/or immune activation is associated with defective myelopoiesis and accumulation of myeloid precursors. ART-induced suppression of HIV-1 replication is associated with normalization of CFU-GM levels.


Environment quality at Maitri station in Antarctica.
A comprehensive study of air, water and soil quality was undertaken during the austral summer of 1999-2000 at the Indian Polar Research Station "Maitri" in compliance with the statutory requirements of the article 3 of Protocol on Environmental Protection to the Antarctic Treaty. The main objective of the study was to assess the impacts of various scientific programs and their associated logistic support facilities on the fragile ecosystem of Antarctica. Identification of major sources of pollution and quantification of pollutants in different environmental components were carried out through an extensive environmental monitoring program spread over a period of 5-7 weeks. Preliminary studies reveal that the levels of pollution are not alarming but there is scope for concern looking into the critical aspects of Antarctic environment and the carrying capacity of the environment surrounding Maitri station.


Sharjah teaching hospital takes shape.
In late 2006, the Ruler of Sharjah, His Highness Sheikh Dr Sultan Bin Mohamed Al Qassimi, approved the start of building of the new Sharjah Teaching Hospital in the United Arab Emirates Jim Cozens, MIHEA, the new facility's engineering services manager, describes the services set to be offered and looks forward to the hospital's opening, scheduled for late this year.


Baicalein Ameliorates Myocardial Ischemia Through Reduction of Oxidative Stress, Inflammation and Apoptosis via TLR4/MyD88/MAPKS/NF-κB Pathway and Regulation of Ca2+ Homeostasis by L-type Ca2+ Channels.
Background: Baicalein (Bai) is the principal ingredient of Scutellaria baicalensis Georgi. Reports concerning the therapeutic advantages in treating cardiovascular diseases have been published. However, its protective mechanism towards myocardial ischemia (MI) is undefined. Objective: The aim of this study was to investigate the protective mechanisms of Bai on mouse and rat models of MI. Methods: Mice were pre-treated with Bai (30 and 60 mg/kg/day) for 7 days followed by subcutaneous injections of isoproterenol (ISO, 85 mg/kg/day) for 2 days to establish the MI model. Electrocardiograms were recorded and serum was used to detect creatine kinase (CK), lactate dehydrogenase (LDH), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and malondialdehyde (MDA). Cardiac tissues were used to detect Ca2+ concentration, morphological pathologies, reactive oxygen species (ROS), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). In addition, the expression levels of Bcl-2-associated X (Bax), B cell lymphoma-2 (Bcl-2), Caspase-3, Toll-like receptor-4 (TLR4), myeloid differentiation protein 88 (MyD88), nuclear factor-kappa B (NF-κB), p-p38, p-extracellular signal-regulated kinase1/2 (p-ERK1/2) and c-Jun N-terminal kinase (p-JNK) were assessed by western blots in myocardial tissues. The effects of Bai on L-type Ca2+ currents (ICa-L), contractility and Ca2+ transients in rat isolated cardiomyocytes were monitored by using patch clamp technique and IonOptix system. Moreover, ISO-induced H9c2 myocardial injury was used to detect levels of inflammation and apoptosis. Results: Bai caused an improvement in heart rate, ST-segment and heart coefficients. Moreover, Bai led to a reduction in CK, LDH and Ca2+ concentrations and improved morphological pathologies. Bai inhibited ROS generation and reinstated SOD, CAT and GSH activities in addition to inhibition of replenishing MDA content. Also, expressions of IL-6 and TNF-α in addition to Bax and Caspase-3 were suppressed, while Bcl-2 expression was upregulated. Bai inhibited protein expressions of TLR4/MyD88/MAPKS/NF-κB and significantly inhibited ICa-L, myocyte contraction and Ca2+ transients. Furthermore, Bai caused a reduction in inflammation and apoptosis in H9c2 cells. Conclusions: Bai demonstrated ameliorative actions towards MI, which might have been related to attenuation of oxidative stress, inflammation and apoptosis via suppression of TLR4/MyD88/MAPKS/NF-κB pathway and adjustment of Ca2+ homeostasis via L-type Ca2+ channels.


Identification of Possible Causative Agents in a Polymedicated Patient Presenting With Toxic Epidermal Necrolysis.
To present the pharmacological evaluation process in a case of a polymedicated patient presenting with toxic epidermal necrolysis (TEN). A 75-year-old Caucasian polymedicated woman had been treated for hip pain with nonsteroidal anti-inflammatory drugs and pregabalin in the months preceding the apparition of an expanding papulo-erythematous rash. She had also started using new medicated eye drops for glaucoma. She presented to the emergency department of a regional hospital where all of her medications were stopped. The patient was transferred and admitted to a tertiary-care teaching hospital's specialized burn unit for significant cutaneous detachment. It was estimated that 70% to 80% of the body surface area was affected. Skin biopsy showed keratinocyte necrosis with a partial detachment of the epidermis leading to a diagnosis of TEN. The reaction ceased to progress 2 days after the discontinuation of her medications. A complete reepithelialization was objectified after 10 days. A series of steps were followed by the hospital pharmacist to determine which drugs were the most probable culprits. A complete pharmacological history was obtained and a timeline for medication use in the 3 months preceding rash apparition was established. A review of the literature was done to determine the drugs' relationships to Steven-Johnson syndrome or TEN. Using the algorithm of drug causality for epidermal necrolysis (ALDEN) score, it was determined that naproxen, pregabalin, and brinzolamide-timolol drops were all possible culprits. A systematic method for pharmacological evaluation of a polymedicated patient with TEN is presented. Naproxen, pregabalin, and brinzolamide-timolol drops were all retained as possible culprits.


Regulated production of type I collagen and inflammatory cytokines by peripheral blood fibrocytes.
We recently described a novel population of blood-borne cells, termed fibrocytes, that display a distinct cell surface phenotype (collagen+/CD13+/CD34+/CD45+), rapidly enter sites of tissue injury, and contribute to scar formation. To further characterize the role of these cells in vivo, we examined the expression of type I collagen and cytokine mRNAs by cells isolated from wound chambers implanted into mice. Five days after chamber implantation, CD34+ fibrocytes but not CD14+ monocytes or CD90+ T cells expressed mRNA for type I collagen. Fibrocytes purified from wound chambers also were found to express mRNA for IL-1beta, IL-10, TNF-alpha, JE/MCP, MIP-1alpha, MIP-1beta, MIP-2, PDGF-A, TGF-beta1, and M-CSF. The addition of IL-1beta (1-100 ng/ml), a critical mediator in wound healing, to fibrocytes isolated from human peripheral blood induced the secretion of chemokines (MIP-1alpha, MIP-1beta, MCP-1, IL-8, and GRO alpha), hemopoietic growth factors (IL-6, IL-10, and macrophage-CSF), and the fibrogenic cytokine TNF-alpha. By contrast, IL-1beta decreased the constitutive secretion of type I collagen as measured by ELISA. Additional evidence for a role for fibrocytes in collagen production in vivo was obtained in studies of livers obtained from Schistosoma japonicum-infected mice. Mouse fibrocytes localized to areas of granuloma formation and connective matrix deposition. We conclude that fibrocytes are an important source of cytokines and type I collagen during both the inflammatory and the repair phase of the wound healing response. Furthermore, IL-1beta may act on fibrocytes to effect a phenotypic transition between a repair/remodeling and a proinflammatory mode.


EZH2 promotes metabolic reprogramming in glioblastomas through epigenetic repression of EAF2-HIF1α signaling.
Cancer cells prefer glycolysis for energy metabolism, even when there is sufficient oxygen to make it unnecessary. This is called the Warburg effect, and it promotes tumorigenesis and malignant progression. In this study, we demonstrated that EZH2, a multifaceted oncogenic protein involved in tumor proliferation, invasion and metastasis, promotes glioblastoma tumorigenesis and malignant progression through activation of the Warburg effect. We observed that HIF1α is a target of EZH2 whose activation is necessary for EZH2-mediated metabolic adaption, and that HIF1α is activated upon EZH2 overexpression. EZH2 suppressed expression of EAF2, which in turn upregulated HIF1α levels. We conclude from these results that EZH2 promotes tumorigenesis and malignant progression in part by activating glycolysis through an EAF2-HIF1α signaling axis.


Towards Bose-Einstein condensation of excitons in potential traps.
An exciton is an electron-hole bound pair in a semiconductor. In the low-density limit, it is a composite Bose quasi-particle, akin to the hydrogen atom. Just as in dilute atomic gases, reducing the temperature or increasing the exciton density increases the occupation numbers of the low-energy states leading to quantum degeneracy and eventually to Bose-Einstein condensation (BEC). Because the exciton mass is small--even smaller than the free electron mass--exciton BEC should occur at temperatures of about 1 K, many orders of magnitude higher than for atoms. However, it is in practice difficult to reach BEC conditions, as the temperature of excitons can considerably exceed that of the semiconductor lattice. The search for exciton BEC has concentrated on long-lived excitons: the exciton lifetime against electron-hole recombination therefore should exceed the characteristic timescale for the cooling of initially hot photo-generated excitons. Until now, all experiments on atom condensation were performed on atomic gases confined in the potential traps. Inspired by these experiments, and using specially designed semiconductor nanostructures, we have collected quasi-two-dimensional excitons in an in-plane potential trap. Our photoluminescence measurements show that the quasi-two-dimensional excitons indeed condense at the bottom of the traps, giving rise to a statistically degenerate Bose gas.


Three-dimensional structure of a schistosome serpin revealing an unusual configuration of the helical subdomain.
Parasitic organisms are constantly challenged by the defence mechanisms of their respective hosts, which often depend on serine protease activities. Consequently, protease inhibitors such as those belonging to the serpin superfamily have emerged as protective elements that support the survival of the parasites. This report describes the crystal structure of ShSPI, a serpin from the trematode Schistosoma haematobium. The protein is exposed on the surface of invading cercaria as well as of adult worms, suggesting its involvement in the parasite-host interaction. While generally conforming to the well established serpin fold, the structure reveals several distinctive features, mostly concerning the helical subdomain of the protein. It is proposed that these peculiarities are related to the unique biological properties of a small serpin subfamily which is conserved among pathogenic schistosomes.


Caplacizumab to treat immune-mediated thrombotic thrombocytopenic purpura.
Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare and life-threatening disease characterized by microangiopathic hemolytic anemia, thrombocytopenia and multiorgan failure, resulting from autoantibody-mediated severe A disintegrin and metalloproteinase with thrombospondin motifs 13 (ADAMTS13) deficiency. In spite of treatment with plasma exchange and immunosuppression, patients remain at risk of exacerbations, refractoriness and death. Caplacizumab (Cablivi; Ablynx, a Sanofi company), a nanobody targeting von Willebrand factor (vWF), has been recently approved in the E.U. and the U.S. as the first therapeutic specifically indicated for the treatment of adults experiencing an episode of iTTP. Caplacizumab blocks the interaction of all multimers with platelets and, therefore, has an immediate effect on platelet aggregation and the ensuing formation and accumulation of platelet-rich microthrombi. This immediate effect of caplacizumab has the potential to protect the patient from tissue ischemia and organ dysfunction while the underlying disease process resolves. We detail here the preclinical and clinical data on caplacizumab for iTTP, including the recent studies that led to approval by the U.S. Food and Drug Administration (FDA) in 2019.


Diagnosis and Management of Patients With Geographic Atrophy Secondary to Age-Related Macular Degeneration: A Delphi Consensus Exercise.
Geographic atrophy (GA) is a progressive and irreversible retinal disease with no comprehensive recommendations for diagnosis or monitoring. We used a Delphi approach to determine consensus in key areas around diagnosis and management of GA. A steering committee of eight retina specialists developed two sequential online surveys administered to eye care professionals (ECPs). Consensus was defined as agreement by ≥ 75% of respondents. Up to 177 ECPs from eight countries completed one or both surveys. Consensus was achieved in several topics related to diagnostic imaging, including the use of optical coherence tomography, and the urgent need for treatments and beneficial interventions to reduce the associated burden. Currently, low-vision aids and smoking cessation are considered the most beneficial interventions. We demonstrate consensus for diagnosis and management of patients with GA including best practices in patient identification and monitoring, and unmet needs. [Ophthalmic Surg Lasers Imaging Retina 2023;54:589-598.].


[Study on effect of drug concentration of "Bushen huayu jiedu fang" drug serum on drug-resistance lung cancer cells with serum pharmacology].
To explore Rh123 ion concentration effect of "Bushen huayu jiedu fang" (BSHYJD) on drug-resistance lung cancer cells, tumor-bearing animal drug-serum pharmacology and flow cytometry method were utilitied. In contrast with normal animal drug serum, BSHYJD drug-serum of tumor-bearing animal would markedly increase Rh123 concentration in drug-resistance lung cancer cells(P < 0.05), but which hasn't marked discrepancy in contrast with normal animal drug-serum(P > 0.05), that indicated BSHYJD drug-serum has increased drug concentration in drug-resistance lung cancer cells.


Translation and validation of the Chinese version of the Japan Frailty Scale.
Frailty is a difficult-to-measure condition that is susceptible to adverse outcomes. The Japan Frailty Scale (JFS) is a tool for assessing frailty status in older adults. This study aimed to translate and culturally adapt the JFS into a Chinese version (JFS-C). The study included 160 older adults as participants. Internal consistency was assessed using Cronbach's alpha, and test-retest reliability was conducted using the intraclass correlation coefficient (ICC). Convergent validity was evaluated by assessing the correlation between JFS-C and the Barthel Index, the Frail scale, and the 36-item Short-Form Health Survey (SF-36). Criterion validity was assessed by comparing JFS-C scores with the Frail scale. JFS-C demonstrated adequate internal consistency (Cronbach's alphas = 0.711) and excellent test-retest reliability over a 7 to 10-day interval (ICC = 0.949). Correlation analysis showed a strong positive correlation between JFS-C and the Frail scale (r = 0.786, p < 0.001), a moderate negative correlation with the Barthel Index (r = -0.598, p < 0.001), and moderate correlations with various subscales of SF-36 (r = -0.574 to -0.661). However, no significant correlations were found between JFS-C and SF-36 mental health (r = -0.363, p < 0.001) or role emotional (r = -0.350, p < 0.001). Based on the reference standard of the Frail scale phenotype (score ≥ 2), the cutoff value for JFS-C was determined to be 3. JFS-C demonstrates good reliability and validity in assessing frailty among the older population in China.


Dielectric and energy storage properties of surface-modified BaTi0.89Sn0.11O3@polydopamine nanoparticles embedded in a PVDF-HFP matrix.
In the most recent electronic and electric sectors, ceramic-polymer nanocomposites with high dielectric permittivity and energy density are gaining popularity. However, the main obstacle to improving the energy density in flexible nanocomposites, besides the size and morphology of the ceramic filler, is the low interfacial compatibility between the ceramic and the polymer. This paper presents an alternative solution to improve the dielectric permittivity and energy storage properties for electronic applications. Here, the poly(vinylidene fluoride-hexafluoropropylene) (PVDF-HFP) matrix is filled with surface-modified BaTi0.89Sn0.11O3/polydopamine nanoparticles (BTS11) nanoparticles, which is known for exhibiting multiphase transitions and reaching a maximum dielectric permittivity at room temperature. BTS11 nanoparticles were synthesized by a sol-gel/hydrothermal method at 180 °C and then functionalized by polydopamine (PDA). As a result, the nanocomposites exhibit dielectric permittivity (εr) of 46 and a low loss tangent (tan δ) of 0.017 at 1 kHz at a relatively low weight fraction of 20 wt% of BTS11@PDA. This is approximately 5 times higher than the pure PVDF-HFP polymer and advantageous for energy storage density in nanocomposites. The recovered energy storage for our composites reaches 134 mJ cm-3 at an electric field of 450 kV cm-1 with a high efficiency of 73%. Incorporating PDA-modified BTS11 particles into the PVDF-HFP matrix demonstrates highly piezo-active regions associated with BTS11 particles, significantly enhancing functional properties in the polymer nanocomposites.


Vancomycin use, dosing and serum trough concentrations in the pediatric population: a retrospective institutional review.
Vancomycin is used primarily for Gram-positive infections. Recommended dosage regimens and targeted therapeutic levels vary between institutions. This study aims to describe therapeutic levels according to initial vancomycin doses and patient's age. A secondary objective was to evaluate appropriateness of vancomycin use in our hospital. A retrospective chart review was conducted at the Children's Hospital of Eastern Ontario. Patients included in this study were classified by age (neonates, infants, children and adolescents) and categorized into those who received vancomycin ≤5 and >5 days. Initial vancomycin dosing regimens and corresponding initial trough levels obtained were evaluated. Initial trough levels drawn in relation to the third, fourth, or fifth doses corresponding to the first course of therapy were analyzed. Acceptable trough levels ranged from 5-20 mg/L. One-hundred-and-sixty-four patients who received intravenous vancomycin in 2013 were included. Of the 229 courses of vancomycin, 190 (83%) were used 5 days or less (mean 4.9 days). Sixteen infants (88.9%) and 21 adolescents (100%), who received vancomycin empiric dosing of 60 mg/kg/day, had initial trough levels >5mg/L. However, in the children's group 20 (37.7%) did not reach levels >5 mg/L. None of vancomycin minimum inhibitory concentration (MIC) values were >1mg/L for the four patients who had infections due to methicillin-resistant Staphylococcus aureus strains. In our institution, initial empiric vancomycin dosing of 60 mg/kg/day resulted in levels ≥5mg/L in most infants and adolescents. It remains unclear why some children aged 1-12 years did not achieve these levels.


Effects of nootropic drugs on brain cholinergic and dopaminergic transmission.
High affinity choline uptake (HACU) in the hippocampus and striatal concentration of dopamine (DA) and homovanillic acid (HVA) as measures of the in vivo acetylcholine and DA turnover, respectively, were estimated in male rats, Long-Evans, following 6-day administration of various nootropics in clinically relevant doses: piracetam and its derivatives pramiracetam and oxiracetam (100 mg/kg/day), pyritinol (50 mg/kg/day). Piracetam treatment was without effect on HACU, but induced significant increase of HVA in the striatum leaving striatal DA concentration unchanged. On the contrary, pyritinol, pramiracetam and oxiracetam increased HACU, but did not change striatal DA and HVA levels.


Antihyperalgesic and antiallodynic effect of sirolimus in rat model of adjuvant arthritis.
Sirolimus is an immunosupressive drug that specifically inhibit the activation of T-lymphocytes. This study was undertaken to investigate whether treatment with sirolimus exert analgesic effect in rat adjuvant-induced arthritis, an animal model of rheumatoid arthritis. Arthritis was induced by a single subcutaneous injection of Freund's complete adjuvant to male Wistar rats that were divided into four groups; control (saline), vehicle (ethanol), sirolimus 0.75 and sirolimus 1.5. Sirolimus (0.75 and 1.5mg/kg/day) was administered intraperitoneally using Monday-Wednesday-Friday dosing schedule for 29 days, this dosing regimen revealed acceptable trough blood concentrations in arthritic rats. Adjuvant inoculation resulted in paw inflammation, hyperalgesia and allodynia as assessed by pletismometer, analgesymeter and dynamic plantar aesthesiometer respectively. Light microscopic evaluation of the arthritic metacarpophalangeal joints revealed synovial hypertrophy with inflammatory cellular infiltration, cartilage destruction and partial subchondral bone resorption. ELISA tests of serum TNF-α, IL-1β or IL-6 did not show any change in arthritic rats, while Western blotting analysis revealed a significant increase in TNF-α (P<0.001), but not IL-1β or IL-6, protein expression in the lumbar spinal cord of arthritic rats. Treatment with sirolimus significantly decreased the arthritic lesions (P<0.001) and paw swelling (P<0.05), alleviated the histological features in the metacarpophalangeal joint, resulted in antihyperalgesic and antiallodynic effects without affecting the locomotor activity and prevented the increased spinal cord TNF-α level (P<0.05). It seems that prevention of the increased TNF-α expression in the spinal cord may partially contribute to the antihyperalgesic effect of sirolimus in adjuvant arthritic rats and sirolimus could be a promising immunosupressive agent in the treatment of arthritic pain.


Race/ethnicity and nonadherence to prescription medications among seniors: results of a national study.
Nonadherence to prescription drugs results in poorer control of chronic health conditions. Because of significant racial/ethnic disparities in the control of many chronic diseases, differences in the rates of and reasons for medication nonadherence should be studied. 1) To determine whether rates of and reasons for medication nonadherence vary by race/ethnicity among seniors; and 2) to evaluate whether any association between race/ethnicity and nonadherence is moderated by prescription coverage and income. Cross-sectional national survey, 2003. Medicare beneficiaries > or = 65 years of age, who reported their race/ethnicity as white, black, or Hispanic, and who reported taking at least 1 medication (n = 14,829). Self-reported nonadherence (caused by cost, self-assessed need, or experiences/side effects) during the last 12 months. Blacks and Hispanics were more likely than whites to report cost-related nonadherence (35.1%, 36.5%, and 26.7%, respectively, p < .001). There were no racial/ethnic differences in nonadherence caused by experiences or self-assessed need. In analyses controlling for age, gender, number of chronic conditions and medications, education, and presence and type of prescription drug coverage, blacks (odds ratio [OR] 1.38; 95% confidence interval [CI] 1.08-1.78) and Hispanics (1.35; 1.02-1.78) remained more likely to report cost-related nonadherence compared to whites. When income was added to the model, the relationship between cost-related nonadherence and race/ethnicity was no longer statistically significant (p = .12). Racial/ethnic disparities in medication nonadherence exist among seniors, and are related to cost concerns, and not to differences in experiences or self-assessed need. Considering the importance of medication adherence in controlling chronic diseases, affordability of prescriptions should be explicitly addressed to reduce racial/ethnic disparities.