The nuclear receptor interaction domain of GRIP1 is modulated by covalent attachment of SUMO-1.
The steroid receptor coactivator (SRC) proteins comprise a well-characterized family of nuclear receptor (NR) coactivators that increase transcriptional activation by NRs via covalent modification of chromatin proteins and recruitment of other coactivators. We have recently shown that the SRC family member GRIP1 interacts with a class of SUMO-1 (small ubiquitin-like modifier 1) E3 ligases, the PIAS proteins, and that the coactivator is subjected to SUMO-1 modifications (sumoylation). In this work, we demonstrate that lysine residues 239, 731, and 788 of GRIP1 serve as principal attachment sites for SUMO-1. Lys-731 and Lys-788 are located in the NR interaction domain (NID), and their substitution by arginines impairs the ability of GRIP1 to colocalize with androgen receptor (AR) in nuclei. Likewise, Lys-731 and Lys-788 mutants of GRIP1 have attenuated ability to enhance AR-dependent transcription and fail to synergize with PIASx beta-mediated activation of AR function, indicating that sumoylation modifies the ability of GRIP1 to function as a steroid receptor coactivator. The Lys-731 sumoylation site is conserved in SRC-3 and SRC-1, and the NIDs of the latter coactivators harbor one or two additional sites matching with the consensus sites for SUMO-1 attachment, respectively, suggesting a more general role for the modification in the regulation of SRC protein activity.


[Dihydromyricetin inhibits proliferation and migration of gastric cancer cells through regulating Akt/STAT3 signaling pathways and HMGB1 expression].
To investigate the inhibitory effects of dihydromyricetin on the proliferation and migration of gastric cancer BGC-823 cells and explore the molecular mechanisms. BGC-823 cells in routine culture were treated with different concentrations of dihydromyricetin (0, 40, 60, 80, 100, and 120 μg/mL) for 24 h, and the changes in cell viability were detected using CCK-8 assay; colony forming assay and Transwell assay were performed to assess the changes in colonyforming and migration abilities of the cells, respectively. The levels of MMP-2 and MMP-9 in the treated cells were determined using ELISA, and Western blotting was used to detect the expressions of E-cadherin, N-cadherin, cyclin D1, cyclin E1, HSP70 and HMGB1 and the phosphorylation levels of Akt and Stat3. CCK-8 assay showed that dihydromyricetin treatment dose-dependently inhibited the viability of BGC-823 cells (P < 0.05). Treatment with dihydromyricetin obviously suppressed the proliferation and migration of BGC-823 cells, significantly reduced the expression levels of cyclin D1, cyclin E1 and Ncadherin, enhanced E-cadherin expression, inhibited the phosphorylation of Akt and stat3, and downregulated HMGB1 expression in the cells. The results of ELISA demonstrated significantly lowered levels of MMP-2 and MMP-9 in dihydromyricetin-treated cells. Dihydromyricetin inhibits the proliferation and migration of BGC-823 cells through suppressing the activation of Akt/stat3 signaling pathways and HMGB1 expression.


CD8+ T lymphocytes and progression to AIDS in HIV-infected men: some observations.
The relationship between CD8+ lymphocyte counts and progression to AIDS was studied in 340 HIV-1-seropositive men participating in a population-based prospective study. Overall, the relative hazard for developing AIDS during 60 months of observation was slightly elevated (1.08, P = 0.003), indicating an 8% increase in risk of progression for every 100 CD8+ cell count increment. When the data were analyzed in relation to date of diagnosis, the relative hazard was depressed (0.90, P less than 0.001) for the period 6 months prior to diagnosis, but was close to 1.0 for the period 6-36 months prior to diagnosis. These findings suggest a complex relationship between CD8+ cell counts and progression to AIDS, with the possibility that various subsets of the CD8+ compartment play different roles.


Large lung bullae in marijuana smokers.
The case histories are presented of four men with multiple large upper zone lung bullae but otherwise relatively preserved lung parenchyma. Each had a history of significant exposure to marijuana. In three of the four cases the tobacco smoking load had been relatively small, suggesting a possible causal role for marijuana in the pathogenesis of this unusual pattern of bullous emphysema.


The phylogenetic structure of the cluster of tobamovirus species serologically related to ribgrass mosaic virus (RMV) and the sequence of streptocarpus flower break virus (SFBV).
Ribgrass mosaic virus (RMV), turnip vein-clearing virus (TVCV) and Youcai mosaic virus (YoMV; formerly designated as oilseed rape mosaic virus; ORMV) belong to the genus Tobamovirus and are arranged in one out of three subgroups because of their common host range, serological cross-reactivity and amino acid composition of their coat proteins. The recently defined species Wasabi mottle virus (WMoV) is closely related to the same subgroup. The distinction of the four species is difficult and the lack of sequence information of a wide range of isolates has led to an unclear nomenclature. To clarify this situation we sequenced the coat protein genes from 18 isolates which were serologically related to members of the species of this cluster. The size of the coat protein was conserved with the exception of one isolate which revealed an N-terminal extension due to the mutation of three stop-codons. Phylogenetic analysis of these CP ORFs resulted in a tree with three clusters each containing at least one of the approved species RMV, TVCV and 1ptYoMV/WMoV in which our isolates were distributed. The tree was congruent and did support the present taxonomic status of species within this subgroup. For practical purpose we developed a subgroup 3 specific primer pair and a species differentiating restriction fragment length polymorphism (RFLP). Sequencing of the genome of Streptocarpus flower break virus (SFBV) which is serologically distantly related to the subgroup 3 viruses revealed a distinct genome organization. Therefore we propose that this virus should be regarded as a member of a species not belonging to any of the subgroups so far established.


[The effects of fitness-type exercise on iron status and hematological status for female college students].
Forty-two female college students underwent fitness-type exercise over a 13 week period. The students exercised an average of two times a week for 30 minute periods at 50% levels of VO2 . max. Iron status and hematological laboratory data were monitored at three points in time; at the initiation of exercise, at the termination of exercise and 3 months later. Serum ferritin levels in a third of the students were lower than 12ng/ml. Red blood cell counts decreased during exercise, and returned to the pre-exercise levels 3 months later. The number of circulatory reticulocytes and mean corpuscular hemoglobin concentration were increased significantly after the exercise and the effects were still observed 3 months later, independent of the iron status. In the lower ferritin group, erythropoietin levels decreased significantly during the post-exercise period. The average serum ferritin levels while showing no significant changes during exercise, increased significantly during the post-exercise period, in the normal ferritin group. We discussed possible mechanisms, among them iron metabolism, by which physical training may facilitate erythropoiesis. However, no definite conclusions have been reached.


ONT-093 (Ontogen).
Ontogen is developing ONT-093 (formerly OC-144-093), a P-glycoprotein pump inhibitor, for the potential reversal of multidrug resistance in patients undergoing cancer chemotherapy. The compound is also being evaluated for its potential enhancement of the oral bioavailability of drugs that are P-glycoprotein substrates requiring either high dosage forms or intravenous administration, and for the potential improvement of central nervous system penetration of P-glycoprotein substrate drugs.


"Just Dance": The Effects of Exergame Feedback and Controller Use on Physical Activity and Psychological Outcomes.
In Asia, dance games are among the most popular types of exergames. Whereas traditional dance-based games emphasize step movements on a dance pad, more recent dance games emphasize intuitive dance movements using simple controllers or players' own bodies to "just dance." However, because of limited space and access, young adults in Taiwan often do not use these games. Popular dance videos on YouTube are more readily available to students because these videos can be accessed on a computer. Therefore, the current study examines the effects of interactivity (the role of feedback) and controller use on participants' physiological and psychological outcomes during exergames. The dance game "Just Dance 3" (Ubisoft, Montreuil, France) was chosen as the stimulus for this study. Participants danced through one song for rehearsal and warm-up, followed by three songs for the experiment, which lasted approximately 12 minutes. One hundred twenty-nine college students participated in a 2×2×2 (interactivity, feedback versus no feedback; controller, with versus without; sex, male versus female) between-subject factorial design. A series of 2×2×2 (interactivity, controller, and sex) analyses of variance showed no significant differences in interaction effects on participants' heart rates, blood pressures, body movements, step counts, or perceived psychological outcomes. Dance game videos without feedback are also effective tools for achieving moderate-level exercise intensity. These videos can supplement the limited access to games in Asian countries, such as Taiwan.


POLRMT as a Novel Susceptibility Gene for Cardiotoxicity in Epirubicin Treatment of Breast Cancer Patients.
Anthracyclines are among the most used chemotherapeutic agents in breast cancer (BC). However their use is hampered by anthracycline-induced cardiotoxicity (AIC). The currently known clinical and genetic risk factors do not fully explain the observed inter-individual variability and only have a limited ability to predict which patients are more likely to develop this severe toxicity. To identify novel predictive genes, we conducted a two-stage genome-wide association study in epirubicin-treated BC patients. In the discovery phase, we genotyped over 700,000 single nucleotide variants in a cohort of 227 patients. The most interesting finding was rs62134260, located 4kb upstream of POLRMT (OR = 5.76, P = 2.23 × 10-5). We replicated this association in a validation cohort of 123 patients (P = 0.021). This variant regulates the expression of POLRMT, a gene that encodes a mitochondrial DNA-directed RNA polymerase, responsible for mitochondrial gene expression. Individuals harbouring the risk allele had a decreased expression of POLRMT in heart tissue that may cause an impaired capacity to maintain a healthy mitochondrial population in cardiomyocytes under stressful conditions, as is treatment with epirubicin. This finding suggests a novel molecular mechanism involved in the development of AIC and may improve our ability to predict patients who are at risk.


Role of endothelial nitric oxide synthase gene polymorphisms in predicting aneurysmal subarachnoid hemorrhage in South Indian patients.
Endothelial nitric oxide synthase (eNOS) gene polymorphisms have been implicated as predisposing genetic factors that can predict aneurysmal subarachnoid hemorrhage (aSAH), but with controversial results from different populations. Using a case-control study design, we tested the hypothesis whether variants in eNOS gene can increase risk of aSAH among South Indian patients, either independently, or by interacting with other risk factors of the disease. We enrolled 122 patients, along with 224 ethnically matched controls. We screened the intron-4 27-bp VNTR, the promoter T-786C and the exon-7 G894T SNPs in the eNOS gene. We found marked interethnic differences in the genotype distribution of eNOS variants when comparing the South Indian population with the reported frequencies from Caucasian and Japanese populations. Genotype distributions in control and patient populations were found to be in Hardy-Weinberg equilibrium. In patients, the allele, genotype and estimated haplotype frequencies did not differ significantly from the controls. Multiple logistic regression indicated hypertension and smoking as risk factors for the disease, however the risk alleles did not have any interaction with these risk factors. Although the eNOS polymorphisms were not found to be a likely risk factor for aSAH, the role of factors such as ethnicity, gender, smoking and hypertension should be evaluated cautiously to understand the genotype to phenotype conversion.


Long-term survival and fate of the leg in de novo intermittent claudication.
The long-term life expectancy and fate of the leg, including progression rate to critical limb ischaemia (CLI), were analysed in de novo patients with intermittent claudication (IC). A prospective cohort study was performed in 1107 patients with de novo IC. The endpoints were overall survival (OS), freedom from major adverse cardiovascular events (MACE), freedom from major adverse cardiovascular and limb events (MACLE), and fate of the leg. The 5-, 10-, 15-, and 20-year rates were 73.3, 47.8, 28.1, and 14.9% for OS, and 63.0, 35.6, 18.5, and 5.7% for freedom from MACE, respectively. In Cox multivariable analysis, body mass index, diabetes, haemodialysis, and C-reactive protein (CRP) level were correlated with OS (P < 0.05). Ankle brachial pressure index, diabetes, coronary artery disease, haemodialysis, and CRP level were independently correlated with freedom from MACE and MACLE. Statins improved mortality, MACE, and MACLE (P < 0.05). Revascularization did not improve mortality and MACE, and femoropopliteal revascularization increased MACLE (P < 0.05). There was no deterioration of claudication in 881 patients (79.6%). Worsening claudication was noted in 211 patients (14.8% per 5 years), and 15 patients (1.1% per 5 years) worsened to CLI. Diabetes and haemodialysis were independent predictors of CLI. A history of cerebral infarction and femoropopliteal revascularization tended to increase CLI. Life expectancy in patients with IC was poor, but the rate of IC progression to CLI was low. Statins improved mortality and morbidity, revascularization did not improve mortality and MACE, and femoropopliteal revascularization reduced freedom from MACLE with a risk of CLI.


Dermatophyte virulence factors: identifying and analyzing genes that may contribute to chronic or acute skin infections.
Dermatophytes are prevalent causes of cutaneous mycoses and, unlike many other fungal pathogens, are able to cause disease in immunocompetent individuals. They infect keratinized tissue such as skin, hair, and nails, resulting in tinea infections, including ringworm. Little is known about the molecular mechanisms that underlie the ability of these organisms to establish and maintain infection. The recent availability of genome sequence information and improved genetic manipulation have enabled researchers to begin to identify and study the role of virulence factors of dermatophytes. This paper will summarize our current understanding of dermatophyte virulence factors and discuss future directions for identifying and testing virulence factors.


[Integrons].
The development of antimicrobial resistance has led to the discovery of many natural mobile elements like transposons and conjugative plasmids. Integrons are carried on plasmids and transposons that potentially increase the dissemination of antibiotic resistance genes among bacterial species. Integrons are genetic elements containing the determinants of a site-specific recombination system. These DNA elements mediate the integration of antibiotic resistance genes into bacteria through the site-specific recombination. Integrons consist of an integrase gene (intl), a recombination site (attl), and one or two promoters responsible for expression of the inserted gene cassettes. Class 1 integrons are the most commonly studied and largely implicated type in the dissemination of antibiotic resistance among clinical isolates. In the last few years, a variety of new gene cassettes coding antibiotic resistance have been described. Having the ability of horizontal transfer of antibiotic resistance genes between interspecies of bacteria, integrons play a dominant role in the development of multiresistance in Enterobacteriaceae. In this review article, classification, structure and expression, epidemiology and clinical importance of integrons, has been discussed.


Enzymic Fractionation of the Stable Carbon Isotopes of Carbon Dioxide by Ribulose-1,5-bisphosphate Carboxylase.
The enzymic fractionation of the stable carbon isotopes of CO(2) (Deltaco(2)) was determined using a purified preparation of ribulose-1,5-bisphosphate (RuBP) carboxylase isolated from cotton (a C(3) plant) leaves. The bicarbonate concentration in the reaction mixture saturated the enzyme and furnished an infinite pool of (12)CO(2) and (13)CO(2) for enzyme fractionation. The RuBP was 96 to 98% pure. The phosphoglycerate synthesized in the reaction mixtures was purified free of RuBP, phosphoglycolate, and other phosphate esters by column chromatography on Dowex 1-Cl(-) resin. The average Deltaco(2) value of -27.1% was determined from five separate experiments. A discussion of the isotope fractionation associated with photosynthetic CO(2) fixation in plants shows that the enzymic fractionation of stable carbon isotopes of CO(2) by RuBP carboxylase is of major importance in determining the delta(13)C values of C(3) plants.


Short periodic applications of the vacuum-assisted closure device cause an extended tissue response in the diabetic mouse model.
The vacuum-assisted closure device is a widely used mechanical modulator of wound healing; however, the optimal time kinetics of application have not been determined. The objective of the study was to optimize the kinetics of vacuum-assisted closure application. Full-thickness wounds in seven diabetic mice per study group were treated with either an occlusive dressing alone, the vacuum-assisted closure device for 6 or 12 hours, or the vacuum-assisted closure device periodically for 4 hours every other day or continuously for 7 days. Wound closure and tissue response were evaluated by macroscopic, histologic, and immunohistochemical analyses on day 7. Wound closure was significantly faster after short initial vacuum-assisted closure (6-hour and 12-hour groups) when compared with continuous treatment. Increased granulation tissue formation was seen in the 12-hour group (2.4-fold increase) and in those treated periodically for 4 hours every other day (3.2-fold increase) compared with the dressing-alone controls. Significant stimulation of cell proliferation was seen after all vacuum-assisted closure patterns (3.6- to 5.3-fold increase), whereas angiogenesis was augmented only after the device was applied for either three times for 4 hours (4.3-fold) or continuously (4.7-fold) when compared with dressing-treated wounds. Treatment three times for 4 hours showed a superior angiogenic effect also when compared with short initial applications (6-hour and 12-hour groups). Short vacuum-assisted closure treatment induced an extended biological response in the wound. A total of 12 hours of periodically applied vacuum-assisted closure reached a similar wound tissue response as continuously applied vacuum-assisted closure for 7 days. These findings suggest new clinical approaches for mechanical wound-healing devices.


Chromodomain helicase DNA-binding protein 2 affects the repair of X-ray and UV-induced DNA damage.
Eukaryotic cells have evolved a variety of parallel and redundant DNA damage response pathways that function in a coordinated fashion to prevent the fixation of DNA damage as mutations. Despite the wealth of knowledge on DNA damage signaling on downstream cellular events, the mechanisms of DNA damage recognition, DNA repair as well as DNA damage signaling in the context of chromatin is poorly understood. Chromodomain helicase DNA-binding proteins (CHD) belong to a group of highly conserved chromatin remodeling proteins that are implicated in regulation of transcription. In an effort to understand the physiological role of one of the CHD members in a mammalian model system, we developed a mutant mouse model for the Chd2 gene. The Chd2 mutant mice are highly susceptible to spontaneous lymphoid tumor formation. In this study, we present evidence that the Chd2 mutant cells are defective in their ability to repair DNA damage induced by ionizing and ultraviolet radiation. Consistent with the role of Chd2 in regulating DNA damage responses, the Chd2 mutant cells are also sensitive to DNA damaging agents in clonogenic assays. In summary, our data suggest that the Chd2 protein is involved in regulating the DNA damage responses at the chromatin level.


Comparative experimental study of cerebral protection during aortic arch reconstruction.
The optimal adjunctive method for cerebral protection during aortic arch repair remains controversial. Retrograde cerebral perfusion, selective cerebral perfusion, and hypothermic circulatory arrest were compared in terms of their effect on cerebral function of mongrel dogs using somatosensory evoked potentials. Brain temperatures were held at 20 degrees C for 90 minutes during cerebral perfusion or circulatory arrest and then rewarmed gradually to normal temperature. Somatosensory evoked potentials completely disappeared as soon as retrograde cerebral perfusion or hypothermic circulatory arrest started and did not recover completely. In the selective cerebral perfusion group, it recovered in all cases. Only 2% of cerebral blood flow and about 3% of the cerebral metabolic rate for oxygen were obtained during retrograde cerebral perfusion compared with the preoperative value. The analysis of adenosine triphosphate and water content of the brain supported these results. Retrograde cerebral perfusion had some advantage for cerebral protection compared with hypothermic circulatory arrest, but could not supply sufficient cerebral blood flow to maintain brain function. Selective cerebral perfusion was the safest method for arch reconstruction that requires cerebral protection for 90 minutes.


Sodium in plants: perception, signalling, and regulation of sodium fluxes.
Although not essential for most plants, sodium (Na(+)) can be beneficial to plants in many conditions, particularly when potassium (K(+)) is deficient. As such it can be regarded a 'non-essential' or 'functional' nutrient. By contrast, the many salinized areas around the globe force plants to deal with toxicity from high levels of Na(+) in the environment and within tissues. Progress has been made in identifying the relevant membrane transporters involved in the uptake and distribution of Na(+). The latter is important in the context of mitigating salinity stress but also for the optimization of Na(+) as an abundantly available functional nutrient. In both cases plants are likely to require mechanism(s) to monitor Na(+) concentration, possibly in multiple compartments, to regulate gene expression and transport activities. Extremely little is known about whether such mechanisms are present and if so, how they operate, either at the cellular or the tissue level. This paper gives an overview of the regulatory and potential sensing mechanisms that pertain to Na(+), in both the context of salt stress and Na(+) as a nutrient.


Recent evolution of bacterial pathogens: the gall-forming Pantoea agglomerans case.
Pantoea agglomerans, a widespread epiphyte and commensal bacterium, has evolved into an Hrp-dependent and host-specific tumorigenic pathogen by acquiring a plasmid containing a pathogenicity island (PAI). The PAI was evolved on an iteron plasmid of the IncN family, which is distributed among genetically diverse populations of P. agglomerans. The structure of the PAI supports the premise of a recently evolved pathogen. This review offers insight into a unique model for emergence of new bacterial pathogens. It illustrates how horizontal gene transfer was the major driving force in the creation of the PAI, although a pathoadaptive mechanism might also be involved. It describes the crucial function of plant-produced indole-3-acetic acid (IAA) and cytokinines (CK) in gall initiation as opposed to the significant but secondary role of pathogen-secreted phytohormones. It also unveils the role of type III effectors in determination of host specificity and evolution of the pathogen into pathovars. Finally, it describes how interactions between the quorum sensing system, hrp regulatory genes, and bacterially secreted IAA or CKs affect gall formation and epiphytic fitness.


Pullout strength of suture anchors: effect of mechanical properties of trabecular bone.
This study investigated the relationships between trabecular microstructure and elastic modulus, compressive strength, and suture anchor pullout strength. Twelve fresh-frozen humeri underwent mechanical testing followed by micro-computed tomography (microCT). Either compression testing of cylindrical bone samples or pullout testing using an Arthrex 5mm Corkscrew was performed in synthetic sawbone or at specific locations in the humerus such as the greater tuberosity, lesser tuberosity, and humeral head. Synthetic sawbone underwent identical mechanical testing and microCT analysis. Bone volume fraction (BVF), structural model index (SMI), trabecular thickness (TbTh), trabecular spacing (TbSp), trabecular number (TbN), and connectivity density were compared against modulus, compressive strength, and pullout strength in both materials. In cadaveric bone, modulus showed correlations to all of the microstructural properties, while compressive and pullout strength were only correlated to BVF, SMI, and TbSp. The microstructure of synthetic bone differed from cadaveric bone as SMI and TbTh showed little variation across the densities tested. Therefore, SMI and TbTh were the only microstructural properties that did not show correlations to the mechanical properties tested in synthetic bone. This study helps identify key microstructure-property relationships in cadaveric and synthetic bone as well as illustrate the similarities and differences between cadaveric and synthetic bone as biomechanical test materials.


Dexamethasone reduces the interstitial fluid pressure in a human colon adenocarcinoma xenograft.
The effect of dexamethasone on interstitial hypertension was evaluated in a human colonic adenocarcinoma. Two weeks after transplantation of the tumor line LS174T into SCID mice, recipients with tumors > 8.5 mm in diameter received one daily injection i.p. on days 1-4, at five different doses in the range of 0.3-30 mg/kg. Controls received saline. The interstitial fluid pressure (IFP) was determined in all tumors pretherapeutically on days 1, 4, and 7. A total of 68 tumors were examined, and in an additional group of 22 mice, the effect of 4-day dexamethasone therapy on blood pressure was evaluated. In the 3-, 10-, and 30-mg/kg dose groups a significant reduction in IFP was found, comparing treated versus controls and individual measurements from day 1 versus day 4. No effects were observed on day 7. A marginal effect was observed after 1.0 mg/kg, whereas 0.3 mg/kg did not affect the IFP. The systemic blood pressure was slightly increased by the dexamethasone therapy, and no treatment related changes in tumor sizes were observed. Our findings indicate that the reversible decrease in tumor IFP by dexamethasone is an effect of a reduced microvascular permeability and vascular hydraulic conductivity in the tumors.


Comparative proteomic analysis of triclabendazole response in the liver fluke Fasciola hepatica.
Control of Fasciola hepatica infections of livestock in the absence of vaccines depends largely on the chemical triclabendazole (TCBZ) because it is effective against immature and adult parasites. Overdependence on a single drug and improper application is considered a significant factor in increasing global reports of fluke resistant to TCBZ. The mode(s) of action and biological target(s) of TCBZ are not confirmed, delaying detection and the monitoring of early TCBZ resistance. In this study, to further understand liver fluke response to TCBZ, the soluble proteomes of TCBZ-resistant and TCBZ-susceptible isolates of F. hepatica were compared with and without in vitro exposure to the metabolically active form of the parent drug triclabendazole sulphoxide (TCBZ-SO), via two-dimensional gel electrophoresis (2-DE). Gel image analysis revealed proteins displaying altered synthesis patterns and responses both between isolates and under TCBZ-SO exposure. These proteins were identified by mass spectrometry supported by a F. hepatica expressed sequence tag (EST) data set. The TCBZ responding proteins were grouped into three categories; structural proteins, energy metabolism proteins, and "stress" response proteins. This single proteomic investigation supported the reductionist experiments from many laboratories that collectively suggest TCBZ has a range of effects on liver fluke metabolism. Proteomics highlighted differences in the innate proteome profile of different fluke isolates that may influence future therapy and diagnostics design. Two of the TCBZ responding proteins, a glutathione transferase and a fatty acid binding protein, were cloned, produced as recombinants, and both found to bind TCBZ-SO at physiologically relevant concentrations, which may indicate a role in TCBZ metabolism and resistance.


Immune and genetic aspects of asthma, allergy and parasitic worm infections: evolutionary links.
There are important parallels in the immunobiology of allergy and asthma, and of the human host's response to parasitic worms. Th-2 immune actions with 'weep and sweep' mucosal biology are common to both - pathological in the first and protective in the second. Common up-regulating genetic variants of Th-2 immunity, notably in IL13 and STAT6, predict increased risk of asthma and allergy, but diminished intensity of infection by Ascaris and Schistosoma. Endemic exposures of humans to parasitic worms may have been one evolutionary force selecting for genetic variants that promote asthma and allergy.


Luminescent cell-penetrating pentadecanuclear lanthanide clusters.
A novel pentadecanuclear lanthanide hydroxy cluster [{Ln15(μ3-OH)20(PepCO2)10(DBM)10Cl}Cl4] (Ln = Eu (1), Tb (2)) featuring the first example with peptoids as supporting ligands was prepared and fully characterized. The solid-state structures of 1 and 2 were established via single-crystal X-ray crystallography. ESI-MS experiments revealed the retention of the cluster core in solution. Although OH groups are present, 1 showed intense red fluorescence with 11(1)% absolute quantum yield, whereas the emission intensity and the quantum yield of 2 were significantly weaker. In vitro investigations on 1 and 2 with HeLa tumor cells revealed an accumulation of the clusters in the endosomal-lyosomal system, as confirmed by confocal microscopy in the TRLLM mode. The cytotoxicity of 1 and 2 toward the HeLa cells is moderate.


Road traffic noise and registry based use of sleep medication.
Road traffic noise has been associated with adverse health effects including sleep disturbances. Use of sleep medication as an indicator of sleeping problems has rarely been explored in studies of the effects of traffic noise. Furthermore, using registry data on sleep medications provides an opportunity to study the effects of noise on sleep where attribution of sleep problems to noise is not possible. We used questionnaire data from the population-based study Health and Environment in Oslo (HELMILO) (2009-10) (n = 13,019). Individual data on sleep medications was obtained from the Norwegian Prescription Database (NorPD). Noise levels (L night) were modeled for the most exposed façade of the building at each participant's home address. Logistic regression models adjusted for potential confounders were used to analyze the association between traffic noise and sleep medication use both for one whole year and for the summer season. The results were reported as changes in the effect estimate per 5 decibel (dB) increase in noise level. We observed no association between traffic noise and sleep medication use during one year [odds ratio (OR) = 1.00; 95% confidence interval (CI): 0.96, 1.04]. For sleep medication use in the summer season, there was a positive, however non-significant association (OR = 1.04; 95% CI: 0.99, 1.10). Among individuals sleeping with the bedroom window open, the association increased slightly and was borderline statistically significant (OR = 1.06; 95% CI: 1.00, 1.12). We found no evidence of an association between traffic noise and sleep medication use during one year. However, for the summer season, there was some suggestive evidence of an association. These findings indicate that season may play a role in the association between traffic noise and sleep, possibly because indoor traffic noise levels are likely to be higher during summer due to more frequent window opening. More studies are, however, necessary in order to confirm this.


Tumor necrosis factor alpha mediates a T cell receptor-independent induction of the gene regulatory factor NF-kappa B in T lymphocytes.
We investigated the molecular basis of the ability of DCEK experimental antigen-presenting cells (APCs) to induce the nuclear form of the transcription factor NF-kappa B in T lymphocytes without engagement of the T cell receptor. We found that NF-kappa B induction did not require contact between the APCs and T lymphocytes and could be achieved by medium conditioned by the APCs. The APCs were found to express low levels of mRNA for TNF alpha. The addition of antibody against TNF alpha blocked the ability of APCs to induce NF-kappa B. These observations were extended by the finding that NF-kappa B was also induced in T lymphocytes separated by a membrane from a mixture of T lymphocytes, splenic APCs and antigen by a TNF alpha-dependent mechanism. Together, these findings suggest that induction of NF-kappa B in antigenically stimulated or 'bystander' T cells may take place through stimulation by TNF alpha as well as in response to T cell receptor occupancy.


Chromosome mapping of five human cardiac and skeletal muscle sarcoplasmic reticulum protein genes.
Fluorescence in situ hybridization (FISH) experiments were performed using genomic and complementary DNA probes in order to determine the location on human chromosomes for five genes expressed in cardiac and skeletal muscle sarcoplasmic reticulum. The chromosome location of each gene was determined in terms of both cytogenetic bands and fractional chromosome length. The ATP2A2 gene, expressing the SERCA2 isoform of the Ca2+ pump, maps to bands 12q23-q24.1, the phospholamban gene (PLN) to 6q22.1, the human skeletal muscle calsequestrin gene (CASQ1) to band 1q21, the cardiac calsequestrin gene (CASQ2) to bands 1p11-p13.3, and the cardiac calcium release channel gene (RYR2) to the interval between band 1q42.1 (distal) and band 1q43 (proximal).


Quantitative Lipidomics and Spatial MS-Imaging Uncovered Neurological and Systemic Lipid Metabolic Pathways Underlying Troglomorphic Adaptations in Cave-Dwelling Fish.
Sinocyclocheilus represents a rare, freshwater teleost genus endemic to China that comprises the river-dwelling surface fish and the cave-dwelling cavefish. Using a combinatorial approach of quantitative lipidomics and mass-spectrometry imaging (MSI), we demonstrated that neural compartmentalization of lipid distribution and lipid metabolism is associated with the evolution of troglomorphic traits in Sinocyclocheilus. Attenuated docosahexaenoic acid (DHA) biosynthesis via the Δ4 desaturase pathway led to reductions in DHA-phospholipids in cavefish cerebellum. Instead, cavefish accumulates arachidonic acid-phospholipids that may disfavor retinotectal arbor growth. Importantly, MSI of sulfatides coupled with immunostaining of myelin basic protein and transmission electron microscopy images of hindbrain axons revealed demyelination in cavefish raphe serotonergic neurons. Demyelination in cavefish parallels the loss of neuroplasticity governing social behavior such as aggressive dominance. Outside the brain, quantitative lipidomics and qRT-PCR revealed systemic reductions in membrane esterified DHAs in the liver, attributed to suppression of genes along the Sprecher pathway (elovl2, elovl5, and acox1). Development of fatty livers was observed in cavefish; likely mediated by an impeded mobilization of storage lipids, as evident in the diminished expressions of pnpla2, lipea, lipeb, dagla, and mgll; and suppressed β-oxidation of fatty acyls via both mitochondria and peroxisomes as reflected in the reduced expressions of cpt1ab, hadhaa, cpt2, decr1, and acox1. These neurological and systemic metabolic adaptations serve to reduce energy expenditure, forming the basis of recessive evolution that eliminates nonessential morphological and behavioral traits and giving cavefish a selective advantage to thrive in caves where proper resource allocation becomes a major determinant of survival.


Prospective evaluation of endoscopic ultrasonography and microscopic examination of duodenal bile in the diagnosis of cholecystolithiasis in 45 patients with normal conventional ultrasonography.
The aim of this study was to prospectively evaluate endoscopic ultrasonography and microscopic examination of duodenal bile in the diagnosis of cholecystolithiasis not detected by conventional ultrasonography. Forty five consecutive patients (26 females, 19 males, mean age: 50 years) with suspected cholecystolithiasis and at least two normal transcutaneous ultrasonography examinations were included. Endoscopic ultrasonographic criteria for the diagnosis of cholecystolithiasis were the presence of stones with or without acoustic shadowing or sludge. Criteria of microscopic examination of bile were cholesterol or bilirubinate crystals or spheroliths. Thirty three patients underwent cholecystectomy and lithiasis was found in gall bladder bile in 24. Twelve patients who were not operated on and were followed up (median: 17 months), had no evidence of cholecystolithiasis. Endoscopic ultrasonography and duodenal bile examination were 96% and 67% sensitive, respectively (p < 0.03). The specificity was not different (86 and 91%, respectively). None of the 16 patients with negative results in both procedures had evidence of cholecystolithiasis. It was found that for the diagnosis of cholecystolithiasis in patients with normal conventional ultrasonography, the sensitivity of endoscopic ultrasonography is higher than that of microscopic examination of duodenal bile. If endoscopic ultrasonography and microscopic examination of duodenal bile are negative, the risk of underdiagnosing cholecystolithiasis is negligible.


Co-occurring mental health and drug dependency disorders: work-force development challenges for the AOD field.
In this paper it is argued that the sheer extent of the co-occurrence of mental health and drug dependency disorders means inevitably that alcohol and other drug (AOD) staff encounter such problems. However, it is contended that the AOD work-force has a number of characteristics that often act as impediments to people with co-occurring disorders receiving, in that sector, appropriate, integrated, 'one-stop-shop' care. Nevertheless, because of the configuration of mental health services in Australia, as essentially acute services for people with severe mental illnesses, there has been, and will continue to be, an overspill of people with mental health disorders and drug problems disorders into the AOD sector. It is there absolutely necessary that initiatives are put into place that support and enable the AOD sector to respond more effectively to people with co-occurring disorders.


Treatment of intracranial (dural) arteriovenous fistulas in unusual locations.
We evaluated retrospectively the treatment modalities and clinical outcome of 14 patients with intracranial dural arteriovenous fistula (AVF) involving cortical veins and dural sinuses except the cavernous and lateral sinuses. The location of arteriovenous shunt was the confluence of the sinuses and superior sagittal sinus (in 2 patients), superior petrosal sinus (1), marginal sinus (1), parasigmoid sinus (1), cortical vein at the anterior fossa (2), cortical vein of the parietal lobe (2), petrosal vein (2), and the cortical vein around the craniocervical junction (3). Of 12 patients who underwent endovascular andlor surgical treatment, five patients were treated only with microsurgery, six only with endovascular therapy, and one with combined surgical and endovascular procedure. Angioanatomical result was complete occlusion of the lesion in all the cases treated with surgery, and 80 to 100% occlusion in cases with endovascular treatment. Clinical outcome was GR in nine patients, MD in two, SD in one, VS in one, and D in one. The natural history of the lesion at each location and angioanatomical feature including the hemodynamic condition in each case should be precisely evaluated to select endovascular, surgical, or a combined procedure for the management of these unusual types of intracranial dural AVF.


An indigenously developed method for sweat collection and estimation of chloride for diagnosis of cystic fibrosis.
An indigenously developed method for sweat collection and titration method for estimation of chloride was validated. The mean difference in estimated chloride value from the known strength of saline in 50 samples was -1.04 +/- 4.13 mEq/L (95% CI: -0.07 to 2.28). The mean difference in the estimated chloride values between two observers when the test was performed on known strengths of saline solution was -2.5 +/- 4.24 mEq/L (95% CI: -3.67 to 1.33). The inter observer variability between two observers when the test was performed on sweat samples obtained from 50 individuals was -1.12 +/- 4.34 mEq/L (95% CI: -2.23 to 0.8 ). Sweat weight of more than 100 mg could be collected in first attempt in 602 of 757 (80%) patient with an average sweat weight of 230 mg. This inexpensive method of sweat collection and chloride estimation has acceptable accuracy and repeatability and can be used in resource poor setting for making a diagnosis of cystic fibrosis.


An imperceptible plastic electronic wrap.
Extremely compliant sub-2-μm sensor films enable temperature mapping on complex 3D objects, like integrated circuits on printed circuit boards, food packages, and on human skin. In their stretchable form, these metal films withstand strains up to 275%. This imperceptible electronic foil technology platform offers new avenues for the design of complex, hybrid rigid-island stretchable-interconnect electronic devices such as RGB light-emitting diode (LED) strips that can be stretched and twisted without impairing their function.


[Sodium thiosulfate--new hope for the treatment of calciphylaxis].
Calciphylaxis is a rare disease primarily affecting patients dependent on dialysis. It is characterised by small vessel media calcification leading to cutaneous ischemia and necrosis. The mortality rate is high with infection and sepsis being the most common causes of death. Calcium salts, vitamin D and high levels of serum calcium and phosphorus increase the risk of calciphylaxis. Current therapies including restoration of mineral homeostasis, wound care and pain control, are not entirely effective. Sodium thiosulfate, by dissolving calcium deposits, is a novel therapeutic choice for calciphylaxis. It has proved successful also in cases refractory to conventional treatment.


Ischemic fasciitis: a juxta-skeletal fibroblastic proliferation with a predilection for elderly patients.
We are reporting six examples of a distinctive reactive fibroblastic proliferation occurring predominantly in elderly bed-ridden or convalescent patients that presents as an ill-defined mass often overlying a bony prominence or in close apposition to the periosteum of bone. Unlike conventional fasciitis, the lesion achieves a relatively larger size and is characterized by a biphasic appearance with an outer fringe of mitotically active fibroblasts and capillaries circumscribing a central area of liquefactive and focally coagulative necrosis. Follow-up information in all patients indicated no evidence of aggressive behavior. We believe these lesions arise on an ischemic basis, similar to a decubitus ulcer, from long-standing or intermittent pressure on the soft tissue structures. Because of their large size and close proximity to bone, they are commonly mistaken for a sarcoma.


Cardiac arrest after severe traumatic brain injury can be survivable with good outcomes.
Resuscitation for traumatic cardiac arrest (TCA) in patients with severe traumatic brain injury (sTBI) has historically been considered futile. There is little information on the characteristics and outcomes of these patients to guide intervention and prognosis. The purpose of the current study is to report the clinical characteristics, survival, and long-term neurological outcomes in patients who experienced TCA after sTBI and analyze the factors contributing to survival. A retrospective review identified 42 patients with TCA from a total of 402 patients with sTBI (Glasgow Coma Scale (GCS) score ≤8) who were admitted to Stony Brook University Hospital, a level I trauma center, from January 2011 to December 2018. Patient demographics, clinical characteristics, survival, and neurological functioning during hospitalization and at follow-up visits were collected. Of the 42 patients, the average age was 45 years and 21.4% were female. Eight patients survived the injury (19.0%) to discharge and seven survived with good neurological function. Admission GCS score and bilateral pupil reactivity were found to be significant indicators of survival. The mean GCS score was 5.3 in survivors and 3.2 in non-survivors (p=0.020). Age, Injury Severity Score, or cardiac rhythm was not associated with survival. Frequent neuroimaging findings included subarachnoid hemorrhage, subdural hematoma, and diffuse axonal injury. TCA after sTBI is survivable and seven out of eight patients in our study recovered with good neurological function. GCS score and pupil reactivity are the best indicators of survival. Our results suggest that due to the possibility of recovery, resuscitation and neurosurgical care should not be withheld from this patient population. Level IV, therapeutic/care management.


Outcomes and associated risk factors for aortic valve replacement in 160 children: a competing-risks analysis.
We sought to define patient characteristics, outcomes, and associated risk factors after aortic valve replacement (AVR) in children. Clinical records from children undergoing AVR from 1974 to 2004 at our institution were reviewed. Competing-risks methodology determined the time-related prevalence of 3 mutually exclusive end states: death, repeated replacement, and survival without subsequent AVR and their associated risk factors. Longitudinal echocardiographic data were analyzed by mixed linear-regression models. Children (n=160) underwent 198 AVRs, with 33 having >1. Competing-risks analysis predicted that 10 years from the initial AVR, 19% had died without subsequent AVR, 34% underwent a second AVR, and 47% remained alive without replacement. Risk factors for death without a second AVR included lower weight (P<0.001) and younger age at AVR (P=0.04), performance of aortic arch reconstruction together with AVR (P=0.03), and nonautograft use (P=0.03). Risk factors for a second AVR included earlier operation year (P=0.04) and implantation of a bioprosthetic or homograft valve (P=0.004). Analysis of serial echocardiographic measurements showed that pulmonary autograft use was associated with slower progression of peak aortic gradient (P=0.002), smaller left ventricular dimension (P=0.04), and decreased prevalence of aortic regurgitation (P=0.04). Mortality and repeated valve replacement are common after initial AVR in children, especially in younger patients and those with bioprosthetic or homograft valves. Pulmonary autograft use is associated with decreased mortality, slower gradient progression, and smaller left ventricular dimension.


Bullying behaviour among Norwegian adolescents: psychiatric diagnoses and school well-being in a clinical sample.
Few studies have focused the association between bullying and psychiatric disorders in clinical samples. The aim of this study was to examine if bullying behaviour was associated with psychiatric disorders and school well-being. The cross-sectional study was part of a health survey at St. Olav's University Hospital. The sample consisted of 685 adolescent patients aged 13-18 years who completed an electronic questionnaire. Clinical diagnoses were collected from clinical records. In this clinical psychiatric sample, 19% reported being bullied often or very often, and 51% reported being bullied from time to time. Logistic regression analyses showed associations between being a victim and having a mood disorder, and between being involved in bullying behaviour and reporting lower scores on school well-being. No difference was found in bullying behaviour on gender, age and SES. The risk of being a victim was high among adolescents in this clinical sample, especially among patients with mood disorders. Any involvement in bullying behaviour was associated with reduced school well-being.


Does management reasoning constitute the backbone of the clinical learning environment?: Conceptual analysis of the existing notions.
Management reasoning is a paradigm whereby learning occurs in a context bound fashion on analysing the biophysical factors existing in the clinical learning environment. In the contemporary medical education forums, much importance is being laid on clinical reasoning and this warrants the appropriate usage of the biomedical knowledge in arriving at the diagnosis. We perceive that clinical reasoning, in pure sense, often doesn't solve the purpose of rendering the best management plan to the patient. This holds stronger when the case is non-linear and highly complex in nature. Management reasoning fills the gap between hypotheses generation, i.e. accomplishing diagnosis and devising management plan. Indeed, it is a complex activity relying on several factors including the physician's perceptual abilities and situated cognition derived from formal and informal learning experiences. In contrast to clinical reasoning, which can be taught using structured scenarios, management reasoning necessitates analysing multitude of factors revolving around a patient and prioritizing those in order to titrate the best possible management plan. This commentary spotlights different dimensions of management reasoning, emphasizes the need of teaching it in the current scenarios, enlists the ways it can be taught, and opens the platform for discussing further on this underemphasized topic.


Willing to pay to save the planet? Evaluating support for increased spending on sustainable development and environmentally friendly policies in five countries.
While the 2016 Paris Agreement is in many ways an important attainment with the potential to represent a milestone in humanity's path towards sustainable development, and avoid thus a potential calamitous and destructive future, the achievement of the goals set in the agreement is a long way off. This paper investigates one of the most important worldwide hurdles frustrating the implementation of the policies required to limit environmental degradation and limit pollution, namely the still insufficient public support for the necessary environmental policies and their associated cost. Using a comparative database generated through an experimental study on tax compliance and policy preferences run in five countries (USA, UK, Italy, Sweden and Romania), I will evaluate five explanatory models of the degree to which people support environmentally friendly policies by accepting higher tax burdens and increased collective solidarity.


i2dash: Creation of Flexible, Interactive, and Web-based Dashboards for Visualization of Omics Data.
Data visualization and interactive data exploration are important aspects of illustrating complex concepts and results from analyses of omics data. A suitable visualization has to be intuitive and accessible. Web-based dashboards have become popular tools for the arrangement, consolidation, and display of such visualizations. However, the combination of automated data processing pipelines handling omics data and dynamically generated, interactive dashboards is poorly solved. Here, we present i2dash, an R package intended to encapsulate functionality for the programmatic creation of customized dashboards. It supports interactive and responsive (linked) visualizations across a set of predefined graphical layouts. i2dash addresses the needs of data analysts/software developers for a tool that is compatible and attachable to any R-based analysis pipeline, thereby fostering the separation of data visualization on one hand and data analysis tasks on the other hand. In addition, the generic design of i2dash enables the development of modular extensions for specific needs. As a proof of principle, we provide an extension of i2dash optimized for single-cell RNA sequencing analysis, supporting the creation of dashboards for the visualization needs of such experiments. Equipped with these features, i2dash is suitable for extensive use in large-scale sequencing/bioinformatics facilities. Along this line, we provide i2dash as a containerized solution, enabling a straightforward large-scale deployment and sharing of dashboards using cloud services. i2dash is freely available via the R package archive CRAN (https://CRAN.R-project.org/package=i2dash).


Compensation claims following road accidents: a six-year follow-up study.
Systematic information was obtained on 96 subjects who were all those seeking compensation from a cohort of 172 consecutive road accident injury victims. Subjects were interviewed immediately after the accident, and again at three months and one year. Further telephone or postal information was obtained about compensation proceedings for up to six years. Compensation proceedings were often prolonged and final settlements were modest and late in relation to the losses suffered. Awards were largely used to make up financial losses. However, they failed to meet needs, especially the considerable early financial problems. There was no evidence that subjects exaggerated their losses; many preferred not to claim or to settle early. There was no evidence that settlement was followed by significant change in clinical state. There was considerable dissatisfaction with the procedures for obtaining compensation. Subjects were often more concerned with recognition of their distress and suffering than with the size of financial settlements. Seeking compensation was not a major predictor of medical and social outcome.


Bisphenol A: a body of evidence supporting exposure reduction.
The "tolerable daily intake" of bisphenol A, established by the European and US regulatory agencies, is based on a small number of reproductive toxicity studies in animals, mostly funded by industry, using protocols that adhere to regulatory guidelines. Many scientists consider these regulatory toxicology tests unsuitable for the evaluation of endocrine disrupters, because they cannot be used to demonstrate the effects of low doses of bisphenol A, observed in dozens of independent studies. Results obtained in studies of high doses of bisphenol A have been extrapolated to predict the effects of low-dose exposure, according to the principle that "the dose makes the poison". The validity of this extrapolation is disputed. Some human studies suggest that bisphenol A causes coronary heart disease, increases the risk of type 2 diabetes, and has harmful effects on reproduction and development. Considerable data from rodent studies suggest that low doses of bisphenol A affect reproduction, lipid metabolism and neurological development, usually following intrauterine or postnatal exposure. In France, the use of bisphenol A in infant feeding bottles has been banned since 30 June 2010, and in food packaging intended for children aged 0 to 3 years since 1 January 2013. The ban is due to be extended to all food packaging as of 1 January 2015. Bisphenol A is not the only substance present in food packaging that could interfere with endocrine function. Too little is known yet about the toxicology of bisphenol A substitutes. Several studies have shown that exposure to bisphenol A in adults and children can be greatly reduced by choosing a varied diet based on fresh foods, and by avoiding the use of plastic tableware. To reduce exposure to bisphenol A and other chemicals with hormonal activity that are present in food packaging, it seems reasonable to encourage the consumption of fresh foods, avoiding canned food and plastic packaging for storing and reheating food and beverages. These precautionary measures are most important for food and beverages intended for pregnant women and young children.


[Prenatal diagnostics of chromosomal aberrations Czech Republic: 1994-2007].
An analysis of prenatal diagnostics efficiency of selected types of chromosomal aberrations in the Czech Republic in 2007. Update of 1994-2007 data according to particular selected diagnoses. Retrospective epidemiological analysis of pre- and postnatal chromosomal aberrations diagnostics and its efficiency. Data on pre- and postnatally diagnosed birth defects in the Czech Republic during 1994-2007 were used. Data on prenatally diagnosed birth defects (and for terminated pregnancies) were collected from particular departments of prenatal diagnostics, medical genetics and ultrasound diagnostics in the Czech Republic, data on birth defects in births from the National Birth Defects Register (Institute for Health Information and Statistics). Total numbers over the period under the study, mean incidences of selected types of chromosomal aberrations and mean prenatal diagnostics efficiencies were analyzed. Following chromosomal aberrations were studied: Down, Edwards, Patau, Turner and Klinefelter syndromes and syndromes 47,XXX and 47,XYY. A relative proportion of Down, Edwards and Patau syndromes as well as other autosomal and gonosomal aberration is presented in figures. Recently, trisomies 13, 18 and 21 present around 70% of all chromosomal aberrations in selectively aborted fetuses, in other pregnancies, "other chromosomal aberrations" category (mostly balanced reciprocal translocations and inversions) present more than 2/3 of all diagnoses. During the period under the study, following total numbers, mean relative incidences (per 10,000 live births, in brackets) and mean prenatal diagnostics efficiency (in %) were found in following chromosomal syndromes: Down syndrome 2,244 (16.58) and 63.37%, Edwards syndrome 521 (3.85) and 79.93%, Patau syndrome 201 (1.49) and 68.87%, Turner syndrome 380 (2.81) and 79.89%, 47,XXX syndrome 61 (0.45) and 59.74%, Klinefelter syndrome 163 (1.20) and 73.65% and 47,XYY syndrome 22 (0.16) and 54.76%. The study gives updated results of incidences analysis of both pre- and postnatally diagnosed chromosomal birth defects in the Czech Republic during the 1994-2007 period. Incidences found in our study correspond (in case of trisomies 13, 18 and 21) with those published widely in literature as well as with those found in large-scale international studies (ICBDSR, EUROCAT). In case of gonosomal aberrations, incidences found in this study are lower that those published, most probably due to a later registration (over 15 years of age of the child) of these diagnoses.


New graduate nurses' experiences of bullying and burnout in hospital settings.
This paper is a report of a study conducted to test a model linking new graduate nurses' perceptions of structural empowerment to their experiences of workplace bullying and burnout in Canadian hospital work settings using Kanter's work empowerment theory. There are numerous anecdotal reports of bullying of new graduates in healthcare settings, which is linked to serious health effects and negative organizational effects. We tested the model using data from the first wave of a 2009 longitudinal study of 415 newly graduated nurses (<3 years of experience) in acute care hospitals across Ontario, Canada. Variables were measured using the Conditions of Work Effectiveness Questionnaire, Negative Acts Questionnaire-Revised and Maslach Burnout Inventory-General Survey. The final model fit statistics revealed a reasonably adequate fit (χ² = 14·9, d.f. = 37, IFI = 0·98, CFI = 0·98, RMSEA = 0·09). Structural empowerment was statistically significantly and negatively related to workplace bullying exposure (β = -0·37), which in turn, was statistically significantly related to all three components of burnout (Emotional exhaustion: β = 0·41, Cynicism: β = 0·28, EFFICACY: β = -0·17). Emotional exhaustion had a direct effect on cynicism (β = 0·51), which in turn, had a direct effect on efficacy (β = -0·34). Conclusion. The results suggest that new graduate nurses' exposure to bullying may be less when their work environments provide access to empowering work structures, and that these conditions promote nurses' health and wellbeing.


Symmetry of the activation of cyclin-dependent kinases in mitogen and growth factor-stimulated T lymphocytes.
The entry of resting T cells into the G1 phase of the cell cycle after stimulation by mitogens is controlled by a series of biochemical events that are independent of growth factors. These events follow the initial signals stimulated through the engagement of the T-cell receptor and include activation of the cyclin-dependent kinases Cdk6, Cdk4, and Cdk2, as well as a transient phosphorylation of the retinoblastoma gene product (p110Rb) by one or several of these proteins. A progression signal such as that delivered by interleukin-2 then induces a second phase of Cdk6, Cdk4, and Cdk2 activation, along with sustained phosphorylation of p110Rb in the activated T cells. This second signal is required to carry the cells into the S phase and beyond. Quantitative and qualitative differences in the expression and activity of these proteins may be critical to maintain the delicate balance that is necessary to ensure the normal progression of T cells through the cell cycle.


Cell type-specific resistance of trigeminal ganglion neurons towards apoptotic stimuli.
Trigeminal ganglion (TG) neurons are important target cells for many alphaherpesviruses and constitute a major site of virus latency and reactivation. Earlier we showed that porcine TG neurons are remarkably more resistant towards (apoptotic) cell death resulting from infection by the swine alphaherpesvirus pseudorabies virus (PRV) compared to a broad range of other primary porcine cell types and that this resistance does not depend on the strongly anti-apoptotic US3 viral protein kinase (Geenen, K., Favoreel, H.W., Nauwynck, H.J., 2005a. Higher resistance of porcine trigeminal ganglion neurons towards pseudorabies virus-induced cell death compared with other porcine cell types in vitro. J. Gen. Virol. 86, 1251-1260). Although other viral anti-apoptotic proteins may be involved in survival of TG neurons during PRV infection, an additional factor may be that TG neurons possess a cell type-dependent capacity to withstand apoptosis compared to other cell types. To investigate this, we treated uninfected porcine TG cultures, swine kidney cells, and porcine superior cervical ganglion (SCG) neurons with several apoptosis-inducing reagents (staurosporine, camptothecin and genistein). None of these reagents were able to trigger substantial apoptotic cell death in TG neurons, whereas non-neuronal TG cells, swine kidney cells, and SCG neurons showed a clear dose-dependent increase in apoptosis using either of these reagents. In conclusion, sensory TG neurons may contain a cell type-specific capacity to withstand different apoptotic assaults, including infection with an alphaherpesvirus.


Natural history of twin-twin transfusion syndrome.
To determine the natural history of pregnancies with twin-twin transfusion syndrome (TTTS). All cases of TTTS at our institution since 1991 and in a MED-LINE search since 1966 were retrospectively reviewed. The prenatal diagnosis of TTTS required the presence of monochorionic/diamniotic placentation (absence of twin-peak sign, thin membrane, single placenta, same sex) and of polyhydramnios (largest pocket > 8 cm) in one sac and oligohydramnios (largest pocket < 2 cm or stuck twin) in the other. Only cases diagnosed at < or = 28 weeks were included. Upon diagnosis, all patients were counseled as to the availability, risks and benefits of serial amniocentesis, laser therapy, septostomy, umbilical cord ligation, and other medical and surgical interventions. Of 29 pregnancies identified at our institution with the above strict criteria for TTTS, 5 (17%) declined in utero therapy and were managed expectantly. The mean gestational age at presentation was 19.2 weeks (range, 16-28) and at delivery, 33.8 weeks (range, 22-41). Four (40%) of the twins survived past the neonatal period, and of the three with follow-up, all are free of neurologic sequelae despite the death in utero of their cotwin. From the literature, 136 fetuses with TTTS as defined above and managed expectantly were identified; 37 (27%) survived; 75% (9/12) of survivors with follow-up are neurologically normal. The most recent four studies have reported survival of untreated cases of 50% (17/34) when diagnosed at < or = 26 weeks and of 63% (20/32) when diagnosed at < or = 28 weeks. The perinatal survival of TTTS pregnancies managed without in utero procedures is approximately 30% overall and 63% in the four most recent series when diagnosed at < or = 28 weeks. The success of in utero therapeutic intervention should be assessed by randomized studies or at least compared to that in similar cases managed without such intervention.


What, me worry? A survey of adolescents' concerns.
Adolescence is generally regarded as a time of transition demanding considerable adaptation. Failing to successfully negotiate the developmental hurdles associated with this period can have serious physical and psychosocial consequences (e.g., teenage pregnancy, suicide, disruption of social relationships, poor school performance). Efforts to identify problems that adolescents typically experience have been useful in facilitating a better understanding of this developmental phase. However, the perceived concerns or worries of adolescents themselves have been neglected as an additional source of useful information. This study assessed the worries of 622 adolescents between the ages of 12 and 20 years on an 80-item self-report measure, the "Things That Worry Me" scale. Findings indicated consistent concerns related to terrorism, adolescents' self-esteem, parents' physical and mental health, and adolescents' dating and sexual relationships. Gender- and race-specific differences are discussed and implications for future research and clinical applications are offered.


Efficacy of a synthetic antimicrobial peptidomimetic versus vancomycin in a Staphylococcus epidermidis device-related murine peritonitis model.
Biofilm-forming Staphylococcus epidermidis is a prevalent cause of peritonitis during peritoneal dialysis. We compared the efficacy of a synthetic antimicrobial peptidomimetic (Ltx21) versus vancomycin in a murine model mimicking a device-related peritonitis. Silicone implants, pre-colonized with an S. epidermidis biofilm, were inserted into the peritoneal cavity of BALB/c mice. Three groups (36 mice in each) with pre-colonized implants received intraperitoneal treatment with Ltx21, vancomycin or placebo. Mice were euthanized on day 3 (n = 12), day 6 (n = 12) or day 8 (n = 12) post-implantation. Controls were mice with sterile implants (n = 18) and mice without surgery (n = 6). Bacterial reductions in cfu were analysed from implants and peritoneal fluid (PF). Inflammatory responses in serum and PF were measured. Vancomycin resulted in a stronger reduction in cfu counts, both on pre-colonized implants and in PF, compared with Ltx21 and placebo. Complete bacterial clearance of the implants was not achieved in any of the groups. The implants pre-colonized with S. epidermidis 1457 resulted in a low-grade peritonitis. We observed, only on day 6, a significant increase in the PF leucocyte count in the group with pre-colonized implants compared with the group with sterile implants (P = 0.0364). Treatment with vancomycin or Ltx21 was not sufficient to achieve complete bacterial clearance of implants, underlining the difficulties of treating such infections. The low-grade infection may attenuate the inflammatory response and contribute to impaired bacterial clearance.


Higher-Level Executive Functions in Healthy Elderly and Mild Cognitive Impairment: A Systematic Review.
Mild Cognitive Impairment (MCI) is a clinical syndrome characterized by a moderate decline in one or more cognitive functions with a preserved autonomy in daily life activities. MCI exhibits cognitive, behavioral, psychological symptoms. The executive functions (EFs) are key functions for everyday life and physical and mental health and allow for the behavior to adapt to external changes. Higher-level executive functions develop from basic EFs (inhibition, working memory, attentional control, and cognitive flexibility). They are planning, reasoning, problem solving, and fluid intelligence (Gf). This systematic review investigates the relationship between higher-level executive functions and healthy and pathological aging, assuming the role of executive functions deficits as a predictor of cognitive decline. The systematic review was conducted according to the PRISMA Statement. A total of 73 studies were identified. The results indicate that 65.8% of the studies confirm significant EFs alterations in MCI (56.8% planning, 50% reasoning, 100% problem solving, 71.4% fluid intelligence). These results seem to highlight a strong prevalence of higher-level executive functions deficits in MCI elderly than in healthy elderly.


Human monocytes synthesize hyaluronidase.
The involvement of hyaluronic acid (HA) oligosaccharides and blood-derived mononuclear cells in inflammatory processes prompted us to determine whether peripheral blood mononuclear cells (PBMC) possess hyaluronidase activity. PBMC were incubated with macromolecular-tritiated HA at pH 3.8 and supernatants were analysed by size exclusion chromatography to reveal digestion of HA. This digestion was due to the CD14-positive (CD14+), adherent, non-specific esterase-positive, subpopulation of PBMC. Hyaluronidase activity (72 kDa) was found in aqueous and non-ionic detergent PBMC extracts but not in the medium in which the cells had been cultured. These results indicate that hyaluronidase is, at least in part, linked to the membrane rather than excreted. Hence, monocytes have one or more hyaluronidases that can generate a pool of active HA fragments within tissues. Hyaluronidase activity was also found in 3/3 myelomonocytic lineage leukaemias but not in 3/3 lymphoblastic leukaemias.


[The role of social networks in exclusive breastfeeding].
The purpose of the study was to explore the network that the social actors form around the mother with a neonate and the roles they play, either as support or as an obstacle of exclusive breast-feeding. We applied a social network survey in two stages: in the first one, we asked mothers with babies under six months of age who had helped them breast-feed their babies and who had had a bearing on not letting them do it. Later, we asked other mothers who had told them to give formula, water, tea or solid food to the babies. With the answers we formed two "cases by actors" matrices. We computed the frequencies to find out those people that most influenced the mother for and against exclusive breast-feeding. We also graphed the results from the matrix to visualize the answers. The maternal grandmother of the child, the physician and the paternal grandmother appeared as those who most positively contributed with exclusive breast-feeding. Paradoxically, they are the same who most influenced its interruption. We were looking for a social network to support exclusive breast-feeding and another one to hinder it, but the two networks turned out to be very similar. The same characters who help a mother to breast-feed are the ones who make her stop. The implication for an intervention program is that it is necessary to strengthen some knowledge and inhibit some other within the same group of people.


Kaempferol inhibitions of corn mitochondrial phosphorylation.
Kaempferol (3, 5, 7, 4'tetrahydroxyflavone) inhibited the rate of state 3 substrate oxidation, but not the state 4 rate. This, along with the kaempferol inhibition of substrate-driven calcium-phosphate deposition, provided evidence that kaempferol was acting specifically on the phosphorylation mechanism and not on electron transfer. Kaempferol, however, did not inhibit ATP-driven contraction while oligomycin did. Comparisons of kaempferol with mersalyl indicated that kaempferol did not inhibit phosphorylation by blocking phosphate transport. Both kaempferol and 2,4-dinitrophenol inhibited calcium-phosphate transport, but kaempferol did not stimulate respiration to the extent that 2,4-dinitrophenol did under acceptorless conditions. Kaempferol had no effect on NADH-driven contraction in a potassium chloride reaction medium. The site of kaempferol effect is thus seen to be unique from oligomycin and more like aurovertin, likely acting before the formation of the phosphorylated high energy intermediate, but not as an uncoupler in the traditional 2,4-dinitrophenol mode.


Policy progress for physician treatment of opiate addiction.
Medical treatment of heroin addiction with methadone and other pharmacotherapies has important benefits for individuals and society. However, regulatory policies have separated this treatment from the medical care system, limiting access to care and contributing to the social stigma of even effective addiction pharmacotherapy. Increasing problems caused by heroin addiction have added urgency to the search for policies and programs that improve the access to and quality of opiate addiction treatment. Recent initiatives aiming to reintegrate methadone maintenance and other addiction pharmacotherapies into medical practice may promote both expanded treatment capacity and increased physician expertise in addiction medicine. These initiatives include changes in federal oversight of the opiate addiction treatment system, the approval of physician office-based methadone maintenance programs for stabilized patients, and federal legislation that could enable physicians to treat opiate addiction with new medications in regular medical practice.


Impact of revascularization and myocardial viability determined by nitrate-enhanced Tc-99m sestamibi and Tl-201 imaging on mortality and functional outcome in ischemic cardiomyopathy.
Nitrate-enhanced perfusion imaging has been shown to detect viability in dysfunctional myocardium, but nitrate-enhanced technetium 99m sestamibi has not been compared with nitrate-enhanced thallium 201. Fifty-six patients with ischemic cardiomyopathy and heart failure (New York Heart Association classes II-IV) were scheduled for revascularization. Through use of a matching 12-segment model, nitrate-enhanced Tl-201 and Tc-99m sestamibi uptake at rest was assessed by 2 sets of blinded investigators. All single photon emission computed tomography data sets were read separately. Additional exercise Tc-99m sestamibi single photon emission computed tomography was performed on a separate day. Myocardial viability was thought to be present when the tracer uptake score was less than 3 (normal, 0; absent, 4). Of the 56 patients scheduled to undergo revascularization, only 23 (41%) underwent the procedure and the remainder continued medical therapy. Functional assessment by rest echocardiography was performed at 21 +/- 8 months, and survival was determined at 40 +/- 18 months. The baseline clinical and hemodynamic parameters were similar in the revascularization (n = 23) and medical therapy (n = 33) groups. Perfusion scores with nitrate-enhanced Tl-201 and Tc-99m sestamibi were similar in dysfunctional segments. Stress Tc-99m sestamibi reversible defects predicted significant improvement in left ventricular function compared with those without defects (P <.01) after revascularization. Cox regression model showed that when at least 5 reversible segments were viable, revascularization produced greater improvements in New York Heart Association class, a better trend toward survival (P =.07 for Tl-201 and P =.06 for Tc-99m), and a significantly greater impact on reverse remodeling. Myocardial viability determined by nitrate-enhanced Tl-201 and myocardial viability determined by Tc-99m sestamibi are equivalent for predicting functional improvements, remodeling, and survival after revascularization in patients with ischemic cardiomyopathy.


Injuries in Australian Army recruits. Part II: Location and cause of injuries seen in recruits.
Three hundred fifty male recruits were randomly allocated to either the standard recruit training program (N = 180) or substituted a weighted-march activity for all formal run periods (N = 170) in the physical training program. All injuries were seen at a single medical facility, and the cause, location, and severity of injury were recorded in the medical documents. Lower-limb injuries constituted 79.8% of all Run injuries and 61.1% of all Walk injuries. Foot (18.9%), knee (16.7%), ankle (13.3%), and shoulder (8.9%) were the most common sites of injury in the Walk group. In the Run group, the most common sites were knee (32.1%), ankle (18.3%), foot (11.9%), and shin (7.3%). There were two stress fractures (tibial) in the Run group and none in the Walk group, giving the Run group an incidence of 1.1%. There were 10 medical discharges in the Walk group and 16 in the Run group. Ten (62.5%) of the Run and 2 (20%) of the Walk discharges were due to lower-limb causes. Of these, only 1 (10%) of the Walk and 4 (25%) of the Run injuries were not considered to be pre-existing conditions. Marching (30.0%), physical training (25.5%), and the obstacle course (11.1%) were the most frequent causes of injury in the Walk group. In the Run group, the leading causes were running (36.6%), physical training (19.2%), and the obstacle course (14.6%). Running was the major cause of knee injury in the Run group (17/35), whereas physical training was the major cause of knee injury in the Walk group (5/15). Running was also the major cause of other lower-limb injuries in the Run group (19/58), whereas marching was the major cause in the Walk group (19/50). Lower-limb injuries were more frequent in the Run group, with running cited as the major cause of these injuries.


Expression of human immunodeficiency virus type 1 gag modulates ligand-induced downregulation of EGF receptor.
Many enveloped viruses use the ESCRT proteins of the cellular vacuolar protein sorting pathway for efficient egress from the cell. Recruitment of the ESCRT proteins by human immunodeficiency virus type 1 (HIV-1) Gag is required for HIV-1 particle budding and egress. ESCRT proteins normally function at endosomal membranes, where they facilitate the downregulation of mitogen-activated receptors such as EGF receptor (EGFR) through multivesicular body biogenesis. It is not known whether the Gag-mediated recruitment of ESCRT proteins functionally depletes the pool of these molecules that is available for the downregulation of EGFR. Here we show that the expression of HIV-1 Gag decreases the rate of EGFR downregulation, as assessed by decreases in the rates of (125)I-EGF and EGFR degradation. The effect of Gag was dependent on the presence of the TSG101 binding motif (PTAP) within the Gag C-terminal p6 domain. Cells expressing HIV-1 Gag retained more EGFR in late endosomes. This effect occurred when Gag was expressed alone from a heterologous promoter and when Gag expression was driven by the HIV-1 long terminal repeat within pHXB2DeltaBalD25S, a noninfectious lentiviral vector. Gag-expressing cells exhibited higher levels of activated mitogen-activated protein kinase for longer times after EGF addition than did cells that did not express HIV-1 Gag. These results indicate that HIV-1 Gag can impinge upon the functioning of the cellular vacuolar protein sorting pathway and reveal yet another facet of the intricate effects of HIV-1 infection on host cell physiology.


Macro and microscopic study of a rare case of Papilliferous Keratoameloblastoma using a stereo zoom microscope.
Papilliferous keratoameloblastoma is an extremely rare variant of ameloblastoma, a benign odontogenic tumor, with only seven cases reported in the English language literature. This variant presents with the metaplastic transformation of stellate reticulum-like cells to the extent of forming papillary structures exhibiting superficial keratinization of varying thickness. This paper describes the pathognomonic macroscopic features of this tumor observed during gross examination under the stereo zoom microscope that differentiate it from the other odontogenic tumors which have not been explored in the previously documented cases. Also, in this paper, a detailed comparison of the macroscopic features observed under the stereo zoom microscope during gross examination with the microscopic features of the histologic section has been described proving to be useful in the histological differential diagnosis of the keratinizing variants of ameloblastoma.


Revision of the structure of Cs2CuSi5O12 leucite as orthorhombic Pbca.
The crystal structure of a hydrothermally synthesized leucite analogue Cs(2)CuSi(5)O(12) has been determined and refined using the Rietveld method from high-resolution synchrotron X-ray and neutron powder diffraction data. This structure is based on the topology and cation-ordering scheme of the Pbca leucite structure of Cs(2)CdSi(5)O(12), and exhibits five ordered Si sites and one ordered Cu tetrahedrally coordinated (T) site. This structure for Cs(2)CuSi(5)O(12) is topologically identical to other known leucite structures and is different from that originally proposed by Heinrich & Baerlocher [(1991), Acta Cryst. C47, 237-241] in the tetragonal space group P4(1)2(1)2. The crystal structure of a dry-synthesized leucite analogue Cs(2)CuSi(5)O(12) has also been refined; this has the Ia3d cubic pollucite structure with disordered T sites.


Genome-wide indel markers shared by diverse Asian rice cultivars compared to Japanese rice cultivar 'Koshihikari'.
Insertion-deletion (indel) polymorphisms, such as simple sequence repeats, have been widely used as DNA markers to identify QTLs and genes and to facilitate rice breeding. Recently, next-generation sequencing has produced deep sequences that allow genome-wide detection of indels. These polymorphisms can potentially be used to develop high-accuracy polymerase chain reaction (PCR)-based markers. Here, re-sequencing of 5 indica, 2 aus, and 3 tropical japonica cultivars and Japanese elite cultivar 'Koshihikari' was performed to extract regions containing large indels (10-51 bp) shared by diverse cultivars. To design indel markers for the discrimination of genomic regions between 'Koshihikari' and other diverse cultivars, we subtracted the indel regions detected in 'Koshihikari' from those shared in other cultivars. Two sets of indel markers, KNJ8-indel (shared in eight or more cultivars, including 'Khao Nam Jen' as a representative tropical japonica cultivar) and C5-indel (shared in five to eight cultivars), were established, with 915 and 9,899 indel regions, respectively. Validation of the two marker sets by using 23 diverse cultivars showed a high PCR success rate (≥95%) for 83.3% of the KNJ8-indel markers and 73.9% of the C5-indel markers. The marker sets will therefore be useful for the effective breeding of Japanese rice cultivars.


Influence of Initial C/N Ratio on Chemical and Microbial Composition during Long Term Composting of Straw.
Shredded straw of Miscanthus was composted in 800-L boxes with different amounts of pig slurry added as nitrogen source. The impact of the different initial C/N ratios (11, 35, 47, 50, and 54) on the composting process and the end product was evaluated by examining chemical and microbiological parameters during 12 months of composting. Low initial C/N ratios caused a fast degradation of fibers during the first three months of composting (hemicellulose: 50-80%, cellulose: 40-60%), while high initial C/N ratios resulted in 10-20% degradation of both hemicellulose and cellulose. These differences were reflected in the microbial biomass and respiration, which initially were higher in low C/N treatments than in high C/N treatments. After 12 months of composting, this situation was reversed. Composts with high initial C/N ratios had high microbial biomass (15-20 mg ATP g-1 OM) and respiration rates (200 mg CO2 h-1 g-1 OM) compared to treatments with low initial C/N ratios (less than 10 mg ATP g-1 OM and 25 mg CO2 h-1 g-1 OM). This could be explained by the microorganisms being nitrogen limited in the high C/N ratio treatments. In the low C/N ratio treatments, without nitrogen limitation, the high activity in the beginning decreased with time because of exhaustion of easily available carbon. Different nitrogen availability was also seen in the nitrification patterns, since nitrate was only measured in significant amounts in the treatments with initial C/N ratios of 11 and 35. The microbial community structure (measured as phospholipid fatty acid, PLFA, profile) was also affected by the initial C/N ratios, with lower fungal/bacterial ratios in the low compared to the high C/N treatments after 12 months of composting. However, in the low C/N treatments higher levels of PLFAs indicative of thermophilic gram-positive bacteria were found compared to the high C/N treatments. This was caused by the initial heating phase being longer in the low than in the high C/N treatments. The different fungal/bacterial ratios could also be explained by the initial heating phase, since a significant correlation between this ratio and heat generated during the initial composting phase was found.


Medicare program; demonstration project to develop a uniform cost reporting system for hospitals--HCFA. Interim final rule with comment period.
This interim final rule with comment period implements the provisions of section 4007(c) of the Omnibus Budget Reconciliation Act of 1987, as amended by section 411(b)(6)(C) of the Medicare Catastrophic Coverage Act of 1988, which require that the Secretary conduct a demonstration project to develop a uniform cost reporting system for hospitals under the Medicare program. Under this rule, all hospitals in the States of California and Colorado are required to participate in this demonstration project. For the duration of the demonstration, those hospitals are required to submit the cost report currently required under Medicare regulations and additional worksheets specifically developed for the demonstration in a uniform, electronic format.


A high throughput electrochemiluminescence assay for the quantification of frataxin protein levels.
Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disease affecting 1 in 50,000 people and is caused by a GAA-trinucleotide expansion in the frataxin gene located on chromosome locus 9q13 which results in a markedly reduced expression of frataxin, a small mitochondrial protein. The exact function of frataxin is still unknown and currently there is no approved treatment available. In the near future there will be a high demand for measuring frataxin protein levels due to the development of therapeutic strategies for FRDA based on manipulating frataxin expression levels in vivo. In this paper we describe the development of an electrochemiluminescence assay (ECLIA) to measure frataxin protein levels in a 96-well plate format. The ECLIA for frataxin is able to measure human and mouse samples and is highly quantitative, accurate and reproducible, with low intra- and inter-assay error throughout a wide working range. The assay has an excellent precision and provides a new tool for the set up of high-throughput screening for basic research and for clinical studies with FRDA patients.


Plasmodium falciparum: immunogenicity of alum-adsorbed clinical-grade TBV25-28, a yeast-secreted malaria transmission-blocking vaccine candidate.
Gozar, M. M. G., Muratova, O., Keister, D. B., Kensil, C. R., Price, V. L., and Kaslow, D. C. 2001. Plasmodium falciparum: Immunogenicity of alum-adsorbed clinical-grade TBV25-28, a yeast-secreted malaria transmission-blocking vaccine candidate. Experimental Parasitology 97, 61-69. The fusion of Pfs25 and Pfs28, two major surface antigens on zygotes and ookinetes of Plasmodium falciparum, as a single recombinant protein (TBV25-28) was previously shown to elicit potent transmission-blocking antibodies in mice. Clinical-grade TBV25-28 was subsequently manufactured and its potency was evaluated in rabbits. Rabbits received three doses of either clinical-grade TBV25H or clinical-grade TBV25-28 adsorbed to alum with or without QS-21. As measured in a standard membrane-feeding assay, addition of QS-21 to the formulations appeared to enhance transmission-blocking potency of rabbit sera after two vaccinations but not after three vaccinations. Surprisingly, TBV25H elicited more potent transmission-blocking antibodies than did TBV25-28, a result strikingly different from those of previous mouse experiments using research-grade TBV25-28. The apparent decrease in potency of clinical-grade TBV25-28 in rabbits appears to reflect an enhancement in potency of clinical-grade TBV25H in a new formulation rather than simply a species difference in immunogenicity of TBV25-28.


A Visual Discrimination of Existing States of Virus Capsid Protein by a Giant Molybdate Cluster.
We report a unique phenomenon, the opposite color response of a giant polyoxometalate, (NH4)42[Mo132O372(CHCOO)30] (H2O)72 ([Mo132]), to the existing states of human papillomavirus (HPV) major capsid protein, L1-pentamer (L1-p), and virus-like particles (VLPs). The color responses originate from the different assembly forms between [Mo132] and the capsid protein. The latter were inspected and separated by using CsCl gradient centrifugation, and validated in detail by sodium dodecyl sulfate-polyacrylamide gel-electrophoresis (SDS-PAGE), dynamic light scattering (DLS), and transmission electron microscopy (TEM) imaging. Furthermore, the intrinsic mechanisms were investigated in-depth by using XPS-based semi-quantitative analysis and well-designed peptides, revealing the critical points of L1 that determine the charge-transfer ratio between Mo(V) to Mo(VI), and consequently, the levels of [Mo132] hypochromic in different assemblies. Such a unique phenomenon is significant as it supplies a colorimetry approach to distinguish the existing states of the HPV capsid protein and would be significant in the quality assay of the HPV vaccine and existing states of other viruses in the future.


Assessment of cognitive load in multimedia learning using dual-task methodology.
In two pilot experiments, a new approach for the direct assessment of cognitive load during multimedia learning was tested that uses dual-task methodology. Using this approach, we obtained the same pattern of cognitive load as predicted by cognitive load theory when applied to multimedia learning: The audiovisual presentation of text-based and picture-based learning materials induced less cognitive load than the visual-only presentation of the same material. The findings confirm the utility of dual-task methodology as a promising approach for the assessment of cognitive load induced by complex multimedia learning systems.


Abundance and diversity of tetracycline resistance genes in soils adjacent to representative swine feedlots in China.
Tetracyclines are commonly used antibiotics in the swine industry for disease treatment and growth promotion. Tetracycline resistance was determined in soils sampled from farmlands in the vicinity of nine swine farms located in three cities in China. Totally, 15 tetracycline resistance (tet) genes were commonly detected in soil samples, including seven efflux pump genes (tetA, tetC, tetE, tetG, tetK, tetL, tetA/P), seven ribosomal protection proteins (RPPs) genes (tetM, tetO, tetQ, tetS, tetT, tetW, tetB/P), and one enzymatic modification gene (tetX). The quantitative real-time PCR was further used to quantify five RPPs genes (tetM, tetO, tetQ, tetW, tetT) and 16S rRNA gene abundances. The concentrations of total tetracyclines (5 typical tetracyclines and 10 of their degradation products) in these soils were measured using liquid chromatography-electrospray tandem mass spectrometry (LC-MS/MS) and were found to range from 5.4 to 377.8 μg·kg(-1) dry soil. Bivariate correlation analysis confirmed that absolute tet gene copies (sum of tetM, tetO, tetQ, tetW genes) were strongly correlated with the concentrations of tetracycline residues (r(2) = 0.45, P < 0.05), ambient bacterial 16S-rRNA gene copies in each soil sample (r(2) = 0.65, P < 0.01), and organic matter in soil (r(2) = 0.46, P < 0.05), respectively. Finally, the phylogenetic analysis on tetM combined with culture-independent molecular techniques revealed at least five genotypes of tetM in nine soil samples.


Recent Topics of Pneumococcal Vaccination: Indication of Pneumococcal Vaccine for Individuals at a Risk of Pneumococcal Disease in Adults.
Pneumococcal disease is one of the most common and severe vaccine-preventable diseases (VPDs). Despite the advances in antimicrobial treatment, pneumococcal disease still remains a global burden and exhibits a high mortality rate among people of all ages worldwide. The immunization program of the pneumococcal conjugate vaccine (PCV) in children has decreased pneumococcal disease incidence in several countries. However, there are several problems regarding the pneumococcal vaccine, such as indications for immunocompetent persons with underlying medical conditions with a risk of pneumococcal disease, the balance of utility and cost, i.e., cost-effectiveness, vaccine coverage rate, serotype replacement, and adverse events. Especially for individuals aged 19-64 at risk of pneumococcal disease, physicians and vaccine providers should make a rational decision whether the patients should be vaccinated or not, since there is insufficient evidence supporting it. We describe this review regarding topics and problems regarding pneumococcal vaccination from the clinician's point of view.


Coinduction of nitric oxide synthase and arginine metabolic enzymes in endotoxin-induced uveitis rats.
The regulation of expression of the arginine-recycling enzymes and arginase isoforms in association with inducible nitric oxide synthase (iNOS) in the eye of endotoxin-induced uveitis (EIU) rats is investigated. An animal model of EIU was created in Wistar rats by intravitreal injection of lipopolysaccharide (LPS). mRNAs for argininosuccinate synthase (AS) and arginase I as well as for iNOS, measured by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), were induced in the eye of EIU rats. iNOS mRNA increased markedly 3 hr after injection, reached a maximum at 6-12 hr, and then decreased at 24 hr. AS mRNA remained little change at 3 hr and increased maximally at 6 hr (by about 3.3-fold), whereas arginase I mRNA increased later and reached a maximum at 12 hr (by about 4.2-fold). iNOS, AS, and arginase I proteins were also induced. AL and arginase II mRNAs remained little changed. In immunohistochemical analysis, iNOS, AS and arginase I were almost colocalized in infiltrated inflammatory cells in the vitreous, iris, ciliary body and inner layers of the retina. In conclusion, AS and arginase I are coinduced with iNOS in infiltrated inflammatory cells in the eyes of EIU rats, and may regulate NO production by changing intracellular concentration of arginine.


Assimilation in visibility: additional evidence.
The present research tested the theory that a less visible target increases in similarity to a more visible simultaneous context, and that therefore the target increases in visibility. This assimilation-in-visibility theory was tested using context + targets that were either 3-line brackets or 2-line right angles, contexts and targets that were the component lines of these context + targets, with the target always the identical single top line. Experiments with a total of 204 participants indicated that the 3-line context + targets resulted in better context + target versus context discriminations than target versus background discriminations than did the 2-line context + targets. This was so for both over-all errors and misses but not false alarms. It is concluded that only the 3-line context + targets increased the visibility of the 1-line target. Additional analysis indicated that the 2-line contexts of the 3-line context + targets were more visible than all the 1-line stimuli. So, the 1-line target assimilated to a simultaneous more visible 2-line context and thereby increased in visibility, thus improving the context + target versus context discrimination. This support for the assimilation-in-visibility theory is of interest because assimilation and contrast in visibility may play a large role in perception.


Truncation of the correlation consistent basis sets: an effective approach to the reduction of computational cost?
The systematic reduction of commonly used basis sets as a means to reduce computational cost is examined for a small test set of molecules, which includes H(2), CH(4), NH(3), H(2)O, HF, and HCN. Coupled cluster with single, double, and quasiperturbative triple excitations calculations were performed using both the correlation consistent basis sets, and a set of systematically reduced basis sets to examine both the impact of the reduction upon the accuracy of the structures and energies, and the computational cost savings achieved. The effect of several truncation scenarios upon basis set convergence is also examined. Overall, for the systems studied, a reduction can occur which preserves the well-established systematic convergence behavior of the correlation consistent basis sets.