MXene-laden bacteriophage: A new antibacterial candidate to control bacterial contamination in water.
In this study, Ti3C2 MXene nanofragments with a size distribution of about 20 nm were laden on the well-characterized bacteriophages via electrostatic bonding, introducing a new antibacterial agent as a modified virus vector to be used in high-risk bacterial environment. At > MIC of MXene, the MXene-functionalized bacteriophage would be much more active in attacking the bacteria because of the high specificity for host receptors' recognition and targeting ability of bacteriophage and bacterial surface negative charge when comparing to the phage alone. Also, the induced positive surface moieties drive MXene nanofragments toward the negative surface charge of bacteria. The main mechanisms are the specific targeting capacity of bacteriophages, often by lysing the host and bursting out, and the physical interaction of MXene nanofragments with the bacterial cell membrane, which may rupture the cell wall in microbial death. The results described that the Ti3C2 MXene significantly enhanced the bacteriophage adsorption rate and stability over long-standing cultivation in aquatic environments providing superior antibacterial efficacy against the bacterial cells target. The Ti3C2 MXene-laden bacteriophage demonstrated a fast, efficient attaching to bacterial host cells, high antibacterial potential, and reduced 99.99% of the artificial contamination in water samples. Interestingly, no re-growth of target bacteria was observed in the samples during the experiment period, and the count of bacteria constantly remained below the detection threshold. This research raises attention in proposing a novel antibacterial agent to be synthesized through a simple one-step technique devoid of shortcomings of post-treatments in conventional antibacterial treatments.


Investigating bacterial infections in Galleria mellonella larvae: Insights into pathogen dissemination and behavior.
The insect Galleria mellonella is an alternative animal model widely used for studying bacterial infections. It presents a wide range of advantages, including its low cost, easy maintenance and lack of ethical constraints. Among other features, their innate immune system is very similar to that of mammals. In this study, we dissected several larvae infected with important human pathogens: Mycobacterium abscessus, Staphylococcus aureus and Pseudomonas aeruginosa. By observing the fat body, gut, trachea, and hemolymph under the microscope, we were able to describe where bacteria tend to disseminate. We also quantified the number of bacteria in the hemolymph throughout the infection course and found significant differences between the different pathogens. With this work, we aimed to better understand the behavior and dissemination of bacteria in the infected larvae.


Identification of a novel Cdc42 GEF that is localized to the PAT-3-mediated adhesive structure.
In the model organism Caenorhabditis elegans, UNC-112 is colocalized with PAT-3/beta-integrin and is a critical protein in the formation of PAT-3-mediated adhesive structure in body-wall muscle cells. However, the signaling pathway downstream of PAT-3/UNC-112 is largely unknown. To clarify the signaling pathway from PAT-3/UNC-112 to the actin cytoskeleton, we searched for and identified a novel Dbl homology/pleckstrin homology (DH/PH) domain containing protein, UIG-1 (UNC-112-interacting guanine nucleotide exchange factor-1). UIG-1 was colocalized with UNC-112 at dense bodies in body-wall muscle cells. UIG-1 showed CDC-42-specific GEF activity in vitro and induced filopodia formation in NIH 3T3 cells. Depletion of CDC-42 or PAT-3 in the developmental stage, by RNAi, prevented the formation of continuous actin filament in body-wall muscle cells. Taken together, these results suggest that UIG-1 links a PAT-3/UNC-112 complex to the CDC-42 signaling pathway during muscle formation.


Subcutaneous sumatriptan in the acute treatment of migraine in patients using dihydroergotamine as prophylaxis. French Migraine Network Bordeaux-Lyon-Grenoble.
The efficacy of sumatriptan, a 5-HT1 receptor agonist, in patients with migraine attacks occurring despite prophylactic treatment with oral dihydroergotamine, was assessed in a double-blind placebo-controlled study involving 76 patients. Thirty-seven patients were treated with a subcutaneous injection of 6 mg sumatriptan self-administered with an auto-injector and 39 with placebo given by the same route. Patients having inadequate relief were allowed to use a second injection of test medication 1 hour later and rescue treatment between 2 hours and 24 hours after the first dose. Headache relief was achieved within 2 hours after sumatriptan in 26 patients (70%) compared to 8 patients (21%) in the placebo group (P < 0.0001). Of these patients, 19 (51%) and 3 (8%) were, respectively, pain free at this time. A second injection of sumatriptan was used by 8 (22%) patients compared to 30 (77%) patients in the placebo group (P < 0.0001), whereas rescue medication was used respectively by 13 (35%) and 22 (58%) patients (P < 0.024). The adverse event profile of sumatriptan was not affected by the concomitant use of dihydroergotamine and side-effects were all minor and transient. Patient satisfaction was significantly higher in the sumatriptan group (75%) compared to patient satisfaction with placebo (16%). These results show that the high efficacy rate of subcutaneous sumatriptan and its safety profile remain unchanged in migraine patients receiving oral dihydroergotamine as prophylaxis.


An overview of environmental and toxicological aspects of aromatic hydrocarbons. III. Xylene.
The commercial product "mixed xylenes" (a technical product generally containing approximately 40% m-xylene and 20% each of o-xylene, p-xylene and ethylbenzene, as well as small quantities of toluene) analogously to toluene is an agent of major chemical and occupational significance. It is produced in very large quantities and is extensively employed in a broad spectrum of applications, primarily as a solvent for which its use is increasing as a "safe" replacement for benzene, and in gasoline as part of the BTX component (benzene-toluene-xylene); xylenes are also frequently used in the rubber industry with other solvents such as toluene and benzene. As individual isomers they are extensively employed in the synthesis of synthetic agents, for example phthalic acid, isophthalic acid, terephthalic acid and dimethylterephthalate, which have very broad applications in the further preparation of phthalate ester plasticizers and components of polyester fiber, film and fabricated items. There is a broad potential for exposure both to industrial workers in the production and use of the xylenes and to the general public (via vehicle exhausts, consumer products, etc). Compared with benzene and toluene, very much less is known of the human health hazards, particularly the chronic effects of xylenes, either as mixed xylenes, as individual isomers or in admixture with other alkylbenzenes. It is of importance to note that coal-based solvents (e.g., xylene) have been suggested to be possible potent lymphocytic leukemogens, such as benzene, in a limited study of the relationship between lymphocytic leukemia and exposures to benzene and other solvents in the rubber industry. Available animal data on the carcinogenicity of xylene(s) are inadequate to permit an evaluation. Mixed xylenes are currently being investigated in a chronic bioassay by the National Toxicology Program. In limited studies thus far, the individual isomers have not been found genotoxic when tested in a number of short-term tests.


Integrin beta1 is involved in the signaling of glial cell line-derived neurotrophic factor.
Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor for the substantia nigra (SN) dopamine (DA) neurons. The transmembrane signaling of GDNF is mediated by a unique receptor system, including the ligand binding receptor GDNF family receptor alpha (GFRalpha) and the transmembrane signaling receptor Ret or neural cell adhesion molecule-140 (NCAM-140). Here, we found that another transmembrane cell adhesion molecule, integrin, a heterodimer consisting of alpha and beta subunits, also mediates the transmembrane signaling of GDNF. The results showed that the level of phosphorylated Src homology 2 domain containing (Shc), which was associated with the cytoplasmic domain of integrin beta1, increased after GDNF administration. Coimmunoprecipitation analysis demonstrated that integrin beta1 could form a complex with GFRalphal. The simulation of molecular modeling showed that four H-bonds were formed between integrin beta1 and GFRalpha. These data indicate that integrin beta1 is involved in the transmembrane signaling of GDNF and suggest that integrin beta1 may be an alternative signaling receptor for GDNF.


Role of antioxidants in buccal mucosa cells and plasma on the incidence and severity of oral mucositis after allogeneic haematopoietic cell transplantation.
Oral mucositis (OM) is known to be a significant complication of chemotherapy preceding haematopoietic cell transplantation (HCT). Antioxidants (AOX) scavenge free radicals, which play a major role in the initiation of OM and may reduce the OM risk. The primary objective of this prospective study was to investigate the association between the incidence and severity of OM (WHO oral toxicity scale) and the AOX status in buccal mucosa cells (BMC) and plasma. The α-tocopherol, ascorbic acid and ß-carotene concentrations in BMC and plasma were assessed at admission in 70 patients with a median age of 58 years before undergoing allogeneic HCT. Severe OM (III-IV), ulcerative OM (II-IV) and no or mild OM (0-I) were documented in 14 (20.0%), 32 (45.7%) and 38 (54.3%) patients, respectively. We observed no significant differences in baseline AOX concentrations in plasma or BMC among the OM groups. However, between patients with at least one plasma AOX beneath the normal range (39/70) and those with all plasma AOX in the normal range (31/70), we noted a trend towards longer duration of parenteral nutrition (PN) during the study period (10 vs. 8 days; p = 0.066). No single AOX, either in plasma or BMC (α-tocopherol, ascorbic acid and ß-carotene), revealed predictive value for the incidence or severity of OM. However, patients with an overall good plasma AOX status tended to require less PN, a common clinical marker for OM, which may be more relevant than any one AOX at reducing the risk of OM.


Simple approach to determining the minimum measurable stress length and stress measurement accuracy in distributed Brillouin sensing.
A simple approach is proposed for quantifying the errors in measuring the Brillouin frequency shifts associated with stresses whose lengths are shorter than the pulse length. The smallest detectable Brillouin frequency shift is thus determined with respect to the size of the stressed sections and the frequency resolution. The lowest detectable frequency shift is found to be approximately 42% of the Brillouin gain natural linewidth. A worst-case iso-error curve that associates the minimum frequency shift to the length of the stressed region is derived. A minimum resolvable frequency shift and minimum detectable stress length are defined with an approach based on a Rayleigh equivalent criterion.


Patient contribution to the medical dialogue and perceived patient-centeredness. An observational study in Japanese geriatric consultations.
Relatively few studies have directly addressed the interaction dynamics and consequences of a companion's presence in the medical visit, and their findings have been contradictory. To examine how patient's contribution to the medical dialogue, with or without the presence of a visit companion, is related to the perception of the medical visit as patient-centered. Observational study using pre- and postvisit questionnaires and audiotape recording of medical visits. One hundred and fifty-five patients aged 65 or over; 63 in medical visits that included the presence of a companion and 82 in visits that did not include a companion. Patient ratings of visit patient-centeredness. Long visits (greater than 10 minutes long) and visits in which patients were verbally active were rated as more patient-centered by patients than other visits. Since patients were generally less verbally active in visits that included a companion, accompanied visits, especially if they were less than 10 minutes long, received lower patient-centered ratings than others. The presence of a companion was not related to length of the visit, suggesting that the verbal activity of the companion was off-set by decreased verbal activity of the patient. Our results have suggested that patients are more likely to perceive their physician and visit as patient-centered when they have an opportunity to engage directly in the medical dialogue. A minimal amount of "talk-time" for patients themselves should be safeguarded even in a short visit, when a companion is present.


The significance of delayed long-loop responses to ankle displacement for the diagnosis of multiple sclerosis.
The present study compares the results of sensory evoked potentials after stimulation of the tibial nerve with measurements of short (M1), medium (M2) and long-loop latency (M3) responses of leg muscles in 42 patients suffering from multiple sclerosis. EMG responses were elicited by a movable platform which was tilted in pitch toe-up around the subject's ankle joint. The short latency response of the triceps surae muscle was nearly always normal in latency. The M2 response was lacking in about 30% of the patients and 10% of normals. The long latency response (M3) in the antagonistic anterior tibial muscle was significantly delayed (beyond 162 msec = AM + 2.5 S) in 69% of the patients. The delayed M3 response was found to indicate demyelination as reliably as the delayed somatosensory evoked potential (66% of the patients). The frequency of coincident results in the entire group was 86%. Additional information is gained in cases where SEPs are normal, but M3 is delayed (7%). Furthermore, patients lacking P40 of the SEP still exhibit M3 responses, the latency of which may be measured (24%). The results favour the assumption that M3 is mediated by a supraspinal pathway.


Light-induced crystallization of cold atoms in a 1D optical trap.
Collective off-resonant scattering of coherent light by a cold gas induces long-range interactions via interference of light scattered by different particles. In a 1D configuration, these interactions grow particularly strong by coupling the particles via an optical nanofiber. Above a threshold pump laser intensity, we predict a phase transition from a homogeneous density to a self-sustained crystalline order. In the dispersive regime, we determine the critical condition for the onset of order as well as the forms of gas density and electric field patterns above threshold. Surprisingly, there can coexist multiple ordered states with distinct appearances.


Role of MAIT cells in metabolic diseases.
MAIT cells are innate-like T cells that are enriched in mucosal sites and tissues including adipose tissue and liver. They play an important role in immunity against microbial pathogens. Recently, it has been reported that MAIT cells could also be important in metabolic diseases and can be involved in setting up and maintaining chronic inflammation. In this review, we give an overview of recent advances in understanding MAIT cells role in the ethology of this diseases.


Factors Affecting Oral Hygiene and Tooth Brushing in Preschool Children, Shiraz/Iran.
Inadequate tooth brushing and inappropriate oral hygiene can lead to dental caries, the most common chronic diseases of childhood with several side effects. To evaluate factors affecting on preschool children's oral hygiene and tooth brushing in Shiraz, Iran. In this cross-sectional study, we selected 453 children registered in Shiraz kindergartens in 2013 by randomized cluster sampling. The children's tooth brushing and oral hygiene were assessed using a reliable and valid questionnaire and Simplified Debris Index (DI-S), respectively. A dental student examined all the children in each kindergarten to determine their DI-S. The relationship between the children's demographic variables and their oral hygiene and tooth brushing status were evaluated. Tooth brushing for 272 children (71.2%) had been started after the age of 2 years. The teeth in 96 children (24.2%) had been brushed lower than once daily. The mean of the children's DI-S was 1.19 ± (0.77). The DI-S of only 126 children (31.8%) was found to be good and very good. After controlling the effect of confounding factors, we found that the children's tooth brushing frequency was significantly associated with the number of children in the family and mothers' employment status. The age at which tooth brushing had been started was significantly associated with the fathers' education. Furthermore, the DI-S was associated with children's age, number of the children in the family, and their mothers' education. Oral hygiene and tooth brushing of the preschool children were not in a desirable status. Interventional procedures, especially educational programs, are recommended for children and their parents. These programs seem to be more necessary for older children, low socioeconomic families, and families with more than one child.


Adhesion of human breast cancer cell line MCF-7 to human vascular endothelial cells in culture. Enhancement by activated platelets.
The interactions of MCF-7 tumor cells with human vascular endothelial cells (EC) and subendothelial extracellular matrices (ECM) were morphologically observed by electron microscopy and quantitatively evaluated by labelling tumor cells with 111Indium-oxine. MCF-7 tumor cells adhered more rapidly to ECM than to the apical surface of a confluent monolayer of EC. The affinity of MCF-7 cells for type-IV collagen was greater than for fibronectin, suggesting that type-IV collagen contributes to the higher rate of adhesion of MCF-7 cells to the subendothelial ECM. Otherwise, the attachment of tumor cells to EC was increased in the presence of both washed platelets and 0.1% citrated platelet-poor plasma (cPPP), a condition accelerating platelet aggregation by tumor cells. The enhancement of MCF-7 adhesion to EC in the presence of platelets and cPPP was completely blocked by the addition of prostacyclin, or hirudin, a specific thrombin inhibitor. In ultrastructural studies, MCF-7 initiated EC retraction, and firm attachment and flattening occurred on exposed ECM. When MCF-7 cells were incubated with platelets and cPPP, most of the tumor cells adhering to the EC and inducing disruption of endothelial monolayer were closely packed and associated with platelet aggregates. MCF-7 cells appeared to adhere more efficiently to exposed subendothelial ECM when they were associated into multicellular aggregates containing platelets and trapped in a fibrin thrombus. Thus, this homologous human system of cultured vascular EC and breast carcinoma line MCF-7 cells may be used to assess anti-aggregant compounds for their ability to alter tumor-cell implantation on EC-lined surfaces.


Consequences of axonal transport blockade by batrachotoxin on mammalian neuromuscular junction. III. An ultrastructural study.
Ultrastructural alterations were analyzed following a single subperineural injection of batrachotoxin (BTX) into the rat peroneal nerve 10-12 mm proximal to its entrance into the extensor digitorum longus (EDL) muscle. At the injection site, most axons underwent reversible changes. Internodal segments of myelin degenerated and were phagocytized without apparent damage to the axon cylinders. Newly forming myelin sheaths were observed by 10 days after injection. Similarly, motor endplates were reversibly altered. By 18 h following injection, most nerve terminals were withdrawn from the postsynaptic elements but reinnervated original endplate regions between 7 and 10 days after injection. These observations explain earlier findings in which muscle membrane potential decreased immediately and spontaneous miniature endplate potentials (MEPPs) and evoked transmitter release were absent from 18 h to 7 days following injection. We suggest that these reversible changes were the result of an insufficient supply of neuronal materials due to BTX-induced blockade of fast axonal transport. Normal physiological function and morphology were restored after fast axonal transport recovered and sufficient quantities of appropriate materials necessary for the maintenance of the nerve terminals and muscle membrane potential were again transported distally from the nerve cell body.


Impacts of gestational age uncertainty in estimating associations between preterm birth and ambient air pollution.
Previous epidemiologic studies utilizing birth records have shown heterogeneous associations between air pollution exposure during pregnancy and the risk of preterm birth (PTB, gestational age <37 weeks). Uncertainty in gestational age at birth may contribute to this heterogeneity. We first examined disagreement between clinical and last menstrual period-based (LMP) determination of PTB from individual-level birth certificate data for the 20-county Atlanta metropolitan area during 2002 to 2006. We then estimated associations between five trimester-averaged pollutant exposures and PTB, defined using various methods based on the clinical or LMP gestational age. Finally, using a multiple imputation approach, we incorporated uncertainty in gestational age to quantify the impact of this variability on associations between pollutant exposures and PTB. Odds ratios (OR) were most elevated when a more stringent definition of PTB was used. For example, defining PTB only when LMP and clinical diagnoses agree yielded an OR of 1.09 (95% confidence interval [CI] = 1.04, 1.14) per interquartile range increase in first trimester carbon monoxide exposure versus an OR of 1.04 (95% CI = 1.01, 1.08) when PTB was defined as either an LMP or clinical diagnosis. Accounting for outcome uncertainty resulted in wider CIs-between 7.4% and 43.8% wider than those assuming the PTB outcome is without error. Despite discrepancies in PTB derived using either the clinical or LMP gestational age estimates, our analyses demonstrated robust positive associations between PTB and ambient air pollution exposures even when gestational age uncertainty is present.


Increased hydrogen peroxide concentration in human tumor cells due to a nitroxide free radical.
Evidence is presented that the nitroxide free radical, TEMPO, at concentrations commonly used to prevent oxidative damage, increases the intracellular hydrogen peroxide concentration. To investigate the origin of this increased hydrogen peroxide concentration, we have incubated various human tumor cell lines with compounds interfering with the generation of active oxygen metabolites. Sodium azide, inhibitor of the respiratory chain, the iron-chelating agent desferrioxamine, superoxide dismutase and catalase had no effect on the hydrogen peroxide concentration. Metyrapone, inhibitor of the cytochrome P450 system, was demonstrated to decrease, but not completely prevent, the hydrogen peroxide production. N-ethylmaleimide, a sulphydryl-bond alkylating agent, was able to completely prevent the increased hydrogen peroxide production. We conclude that, by increasing the cellular hydrogen peroxide concentration, TEMPO exerts a pro-oxidant effect. This increase in hydrogen peroxide production seems to be mediated by the induction of oxidase activity in the cytochrome P450 system, but other cellular systems involved in electron transport may also play a role.


Association of human and bovine beta 2-microglobulins with detergent solubilized HLA-A,B antigens.
The association of human and bovine beta 2-microglobulins with detergent solubilized HLA-A,B antigens was analyzed by a direct binding assay using radiolabeled beta 2-microglobulin and an immunoadsorbent containing a monoclonal antibody to the HLA-A,B heavy chains. Binding of beta 2-microglobulin to HLA-A,B heavy chains could be saturated with respect to the amount of membrane glucoprotein in the system and reached steady state after 6 h at 37 degrees C. Inhibition of [125I]beta 2-microglobulin binding to HLA-A,B heavy chains by beta 2-microglobulin purified from human urine or bovine colostrum resulted in identical inhibition curves and apparent dissociation constants of 1 X 10(-8) M. This evidence suggests that beta 2-microglobulins from different species have similar binding sites for HLA-A,B heavy chains.


Lane change behavior with a side blind zone alert system.
This in-traffic study explored the effect of a side blind zone alert (SBZA) system on driver lane change behavior. Such a system may help drivers avoid lane change crashes by warning them with a side mirror display when a vehicle is detected in their blind zone. Participants drove with and without the SBZA system enabled, and were instructed to evaluate vehicle ride characteristics and only given an "incidental" system explanation. Overall, drivers failed to execute "over the shoulder" (blind zone) glances for 68 and 85% of the left and right lane changes, respectively. This suggests that the SBZA display provides information to the driver that often fails to be obtained via over the shoulder glances. In addition, when the SBZA system was enabled there was a 31% reduction in left lane changes attempted without the driver checking the left mirror, and a 23% reduction in right lane changes attempted without the driver checking the inside mirror. These results, coupled with the assumption that "did not see other vehicle" is a principal causal factor in many lane change crashes, suggests that the SBZA system may assist drivers in avoiding lane change crashes.


Laparoscopic hyperthermic intraperitoneal chemotherapy for the management of advanced peritoneal carcinomatosis.
The role of laparoscopic HIPEC has been reported by several centers around the world as a promising and appealing therapeutical alternative in the management of patients suffering of advanced intra-abdominal malignancies and peritoneal carcinomatosis. Laparoscopic HIPEC is implemented as a neoadjuvant and adjuvant therapeutical modality before and after open cytoreductive surgery. The diagnostic and therapeutical impact of laparoscopic HIPEC is well appreciated and generally is associated with many advantages when compared to classical open HIPEC and simultaneous open cytoreductive surgery.


Safety and effectiveness of a novel generator algorithm for bipolar vessel sealing: a randomised controlled chronic animal study.
Electrosurgical vessel sealers are gradually replacing conventional techniques such as ligation and clipping. Algorithms that control electrosurgical units (ESU), known as modes, are important for applications in different surgical disciplines. This chronic porcine animal study aimed to evaluate the safety and effectiveness of the novel thermoSEAL electrosurgical vessel sealing mode (TSM). The BiClamp® mode (BCM) of the renowned VIO® 300 D ESU served as control. BCM has been widely available since 2002 and has since been successfully used in many surgical disciplines. The TSM, for the novel VIO® 3 ESU, was developed to reduce sealing time and/or thermal lateral spread adjacent to the seal while maintaining clinical success rates. The primary aim of this study was to investigate the long-term and intraoperative seal quality of TSM. The BiCision® device was used for vessel sealing with TSM and BCM in ten German Landrace pigs which underwent splenectomy and unilateral nephrectomy during the first intervention of the study. The seals were cut with the BiCision® knife. Ninety-nine arteries, veins and vascular bundles were chronically sealed for 5 or 21 days. Thereafter, during the second and terminal intervention of the study, 97 additional arteries and veins were sealed. The carotid arteries were used for histological evaluation of thermal spread. After each survival period, no long-term complications occurred with either mode. The intraoperative seal failure rates, i.e. vessel leaking or residual blood flow after the first sealing activation, were 2% with TSM versus 6% with BCM (p = 0.28). The sealing time was significantly shorter with TSM (3.5 ± 0.69 s vs. 7.3 ± 1.3 s, p < 0.0001). The thermal spread and burst pressure of arteries sealed with both modes were similar (p = 0.18 and p = 0.61) and corresponded to the histological evaluation. The measured tissue sticking parameter was rare with both modes (p = 0.33). Tissue charring did not occur. Regarding the cut quality, 97% of the seals were severed in the first and 3% in the second attempt (both with TSM and BCM). The novel TSM seals blood vessels twice as fast as the BCM while maintaining excellent tissue effect and clinical success rates. Not applicable.


HCV-related proteins activate Kupffer cells isolated from human liver tissues.
It was reported from this laboratory that Kupffer cells (KCs) were activated in patients infected with HCV. Since dendritic cells, monocytes, and macrophages were activated by stimulation with HCV-related proteins, the specific aim of this study was to investigate the role of HCV-related proteins in activation of KCs, the signal pathway of activation of KCs mediated by Toll-like receptor (TLR) 4, and the influence of HCV infection on function of KCs. Kupffer cells isolated from non-cancerous surgical specimen were co-cultured with HCV-related proteins (Core, NS3, NS4, and NS5), and production of cytokines (TNF-α, IL-1β, and IL-10) and hydrogen peroxide were assessed. Furthermore, effects of neutralization antibodies against the TLR2, TLR3, or TLR4, and cytochalasin B on the production TNF-α by KCs were investigated. Kupffer cells produced markedly a proinflammatory cytokine TNF-α by stimulation with all HCV-related proteins studied, and values were as same as production by KCs stimulated with LPS. Importantly, this production in the case of NS3 was significantly blunted by about 60% by neutralization antibodies against the TLR4, but not cytochalasin B. Production of TNF-α by isolated KCs stimulated with LPS was significantly greater in the HCV-infected livers than the HCV/HBV-negative livers. These results indicated that HCV-related proteins may cause prolonged activation of KCs in the HCV-infected liver, leading to accumulation of inflammatory cytokines that contribute to DNA damage and carcinogenesis. Furthermore, function of KCs was difference between patients infected with and without HCV infection.


Emergency medical services operations during civil unrest: Best practices from lessons learned.
During periods of civil unrest, emergency medical services (EMSs) clinicians will be called upon to provide care to those impacted, including those who are actively instigating violence. Working during periods of civil unrest poses significant operational and security challenges to EMS leadership and clinicians. This review provides best practices for EMS operating during periods of civil unrest through analysis of after action reports from Baltimore, Maryland; Charlottesville, North Carolina; Minneapolis, Minnesota; and Washington, DC.


Regulation of prostanoid synthesis in microglial cells and effects of prostaglandin E2 on microglial functions.
Brain prostanoid levels are normally low but can increase after ischemia and during inflammatory and infectious diseases. High prostanoid levels can affect brain function in several ways. In particular, prostaglandin E2 (PGE2) might exert both immunodepressive and proinflammatory actions. The present short review focuses on the regulation of prostanoid synthesis in microglial cultures and on the possible role of PGE2 in the down-regulation of microglial activation induced by lipopolysaccharide (LPS). Our studies were carried out using purified mouse or rat microglial cultures. LPS induced a dose-dependent expression of the inducible isoform of cyclooxygenase (COX-2), both in neonatal and adult microglial cultures. In the latter, the inducibility of COX-2 increased with time in culture, paralleling the acquisition of a more 'activated' microglial phenotype, and appeared to account for the time-dependent increase in the PGE2/TXB2 production ratio. The LPS-induced COX-2 expression and prostanoid production were down-regulated by potentially neurotoxic agents, such as nitric oxide (NO), the proinflammatory cytokine IFN-gamma (which acted both directly and indirectly, through its NO-inducing activity) and the HIV regulatory protein tat. On the other hand, COX-2 expression was up-regulated by the macrophage-deactivating cytokine TGF-beta 1, by exogenous PGE2 itself, which acted through EP2 receptors linked to cyclic AMP generation, and by non steroidal anti-inflammatory drugs. Interestingly, PGE2 utilized the same EP2 receptor-mediated signal transduction mechanism to down-regulate the expression of the inducible NO synthase and the production of NO. Largely, but not exclusively, through its effect on cyclic AMP, PGE2 can also: i) depress the expression of major histocompatibility complex class II antigens and of the costimulatory molecule B7-2; ii) down-regulate TNF and up-regulate IL-10 microglial production; iii) inhibit microglial IL-12 secretion. These observations, together with literature data on in vivo models of central nervous system (CNS) diseases, suggest a neuroprotective role of PGE2 in pathological conditions.


Nitrous oxide as a humane method for piglet euthanasia: Behavior and electroencephalography (EEG).
The search for humane methods to euthanize piglets is critical to address public concern that current methods are not optimal. Blunt force trauma is considered humane but esthetically objectionable. Carbon dioxide (CO2) is used but criticized as aversive. This research sought to: 1) evaluate the aversiveness of inhaling nitrous oxide (N2O; 'laughing gas') using an approach-avoidance test relying on the piglet's perspective, and 2) validate its humaneness to induce loss of consciousness by electroencephalography (EEG). The gas mixtures tested were N2O and air (90%:10%; '90 N'); N2O, oxygen and air (60%:30%:10%; '60 N'); and CO2 and air (90%:10%; '90 C'). Experiment 1 allowed piglets to walk freely between one chamber filled with air and another prefilled with 60 N or 90 N. All piglets exposed to 60 N lasted for the 10 min test duration whereas all piglets exposed to 90 N had to be removed within 5 min because they fell recumbent and unresponsive and then started to flail. Experiment 2 performed the same test except the gas chamber held N2O prefilled at 25%, 50%, or 75% or CO2 prefilled at 7%, 14%, or 21%. The test was terminated more quickly at higher concentrations due to the piglets' responses. Time spent ataxic was greater in the middle concentration gradients. Flailing behavior tended to correlate with increasing concentrations of CO2 but not N2O. Experiment 3, using the minimal anesthesia model, showed that both 90 N and 90 C induced isoelectric EEG, in 71 and 59 s respectively, but not 60 N within 15 min. The EEG results together with the observed behavioral changes reflect differences in the animal's perceptive experience. The implications for animal welfare are that N2O is much less aversive than CO2, and 90% N2O can euthanize piglets.


On the mechanism of histamine release from sodium fluoride-activated mouse mast cells.
We have found that sodium fluoride-induced histamine release from mouse mast cells occurs in two separate steps, activation in the presence of fluoride and absence of calcium, and secretion triggered by calcium. The amount of released histamine was dependent either on the time of cell exposure to fluoride or on the final fluoride concentration in the incubation medium. The secretory step depends on the concentration of extracellular calcium; it increased as the concentration of calcium was increased. However, a substantial part of the release was both calcium and energy independent. This part, probably cytotoxic, increased markedly at the highest concentration and with extended times of cell exposure to fluoride. Among other divalent cations tested only strontium could partly substitute calcium to trigger secretion. The activating action of fluoride slowly decayed with time and addition of calcium for up to 2 h caused histamine release. Both steps were dependent on temperature and pH and were inhibited by antimycin A, suggesting that the reaction was enzymatic. The action of fluoride on mouse mast cells closely resembles its action on rat mast cells; however, some differences were also observed.


Differences in cardiovascular morbidity and mortality between previously known and newly diagnosed adult diabetics.
498 diabetics were discovered in a survey of ischaemic heart disease in 10,059 men aged 40 years and over in Israel. -The diabetics were divided into previously known and newly diagnosed. -During a 5 year follow-up period, the incidence rates of fatal and non-fatal myocardial infarction and the incidence of intermittent claudication were considerably greater in both groups of diabetics than in non-diabetics. The frequency of hypertension and left ventricular hypertrophy was about the same in both groups, and in non-diabetics. -However, the pattern of increased morbidity for angina pectoris and the increased rate of sudden death is seen only in the previously diagnosed diabetics. Different pathological mechanisms might be responsible for angina pectoris and sudden death, as compared to myocardial infarction and these might be related in diabetics to the duration and severity of the disease.


A tumor suppressor role of the Bub3 spindle checkpoint protein after apoptosis inhibition.
Most solid tumors contain aneuploid cells, indicating that the mitotic checkpoint is permissive to the proliferation of chromosomally aberrant cells. However, mutated or altered expression of mitotic checkpoint genes accounts for a minor proportion of human tumors. We describe a Drosophila melanogaster tumorigenesis model derived from knocking down spindle assembly checkpoint (SAC) genes and preventing apoptosis in wing imaginal discs. Bub3-deficient tumors that were also deficient in apoptosis displayed neoplastic growth, chromosomal aneuploidy, and high proliferative potential after transplantation into adult flies. Inducing aneuploidy by knocking down CENP-E and preventing apoptosis does not induce tumorigenesis, indicating that aneuploidy is not sufficient for hyperplasia. In this system, the aneuploidy caused by a deficient SAC is not driving tumorigenesis because preventing Bub3 from binding to the kinetochore does not cause hyperproliferation. Our data suggest that Bub3 has a nonkinetochore-dependent function that is consistent with its role as a tumor suppressor.


Accelerated Stress Test Method for the Assessment of Membrane Lifetime in Vanadium Redox Flow Batteries.
An accelerated stress test (AST) method was developed to estimate the lifetime of ion-exchange membranes in a vanadium redox flow battery. The oxidative VO2+ ions present in the charged positive electrolyte are the predominant stressor causing loss of functional groups and membrane conductivity. Membrane aging was accelerated in ex situ tests by exploiting elevated temperatures and the increased oxidative strength of Ce4+. Acceleration factors were determined on the basis of the analysis of aged radiation grafted g(S-AN) membranes. The degradation in a Ce4+ solution was found to be ∼4 times faster than in VO2+. The highest acceleration factor of ∼200 was found for the degradation with Ce4+ at 80 °C. The degradation reaction present in the accelerated stress test showed a similar activation energy of ∼50 kJ/mol in VO2+ and Ce4+ solutions, suggesting a similar reaction pathway. The applicability of the test was further evaluated with the second membrane, g(AMS-MAN). Its lifetime was estimated based on the accelerated stress test and acceleration factors previously determined for the g(S-AN) membrane and compared to the lifetime projected from an extended cycling experiment in the cell. The two values were in the same range of ∼4000 h. The proposed AST can serve as a basis for predictive modeling of membrane lifetime in vanadium redox flow batteries. The potential of the method and the limitations are discussed.


Selection principles for Gaia.
The Gaia hypothesis considers the life-environment coupled system as a single entity that acts to regulate and maintain habitable conditions on Earth. In this paper we discuss three mechanisms which could potentially lead to Gaia: Selection by Survival, Sequential Selection and Entropic Hierarchy. We use the Tangled Nature Model of co-evolution as a common framework for investigating all three, using an extended version of the standard model to elaborate on Gaia as an example of an entropic hierarchy. This idea, which combines sequential selection together with a reservoir of diversity that acts as a 'memory', implies a tendency towards growth and increasing resilience of the Gaian system over time. We then discuss how Gaian memory could be realised in practice via the microbial seed bank, climate refugia and lateral gene transfer and conclude by discussing testable implications of an entropic hierarchy for the study of Earth history and the search for life in the universe. This paper adds to the existing taxonomy of Gaia hypotheses to suggest an "Entropic Gaia" where we argue that increasing biomass, complexity and enhanced habitability over time is a statistically likely feature of a co-evolving system.


Structure-function relationships in high-density docosylsilane bonded stationary phases by Raman spectroscopy and comparison to octadecylsilane bonded stationary phases: effects of aromatic compounds.
The effects of four aromatic compounds on alkyl chain conformational order for a series of high-density docosylsilane (C22) stationary phases with surface coverage ranging from 3.61 to 6.97 micromol/m2 are investigated using Raman spectroscopy. Aromatic compounds studied include benzene-d6, toluene-d8, aniline-d7 and anisole-d8. In general, these aromatic solvents decrease the conformational order of the C22 phases relative to air suggesting partitioning of the aromatics into the alkyl chains of these stationary phases. Changes in alkyl chain conformational order are linearly dependent on the solvent hydrophobicity parameter, log K ow, and are also dependent on stationary phase properties (i.e. polymerization method and surface coverage). A comparison is made between C22 and C18 bonded phase systems. The conformational order of the alkyl chains in a mixed solute/mobile phase system is also studied using 80% methanol/water as the mobile phase and aniline-d7, anisole-d8 or toluene-d8 as solutes. Collectively, the Raman spectroscopic evidence at the molecular level suggests interaction of these aromatic species with the bonded alkyl chains through partitioning.


Lack of human IgE cross-reactivity between mite allergens Blo t 1 and Der p 1.
The group 1 mite allergens are the most significant indoor allergens and they belong to the papain-like cysteine protease family. To date there is only one published report on the isolation and characterization of group 1 allergens from Blomia tropicalis mites. The aims of the study are to determine the cross-reactivity between group 1 allergens and to evaluate their clinical importance in allergic patients. The full-length Blo t 1 gene was obtained by SMART RACE cDNA amplification method using gene-specific primers. The sequence alignment was performed using LOOK followed by three-dimensional homology modeling. The cDNA was expressed in Pichia pastoris as a secretory protein. Identification of native Blo t 1 in crude mite and spent mite medium extracts was done by Western immunoblot using monoclonal antibody. Allergenicity of recombinant Blo t 1 and native Der p 1 was examined by human IgE ELISA with 80 asthmatic sera. The cDNA sequence consists of 1105 base pairs, including 5'- and 3'-untranslating regions, encoding an open reading frame of 330 amino acid residues. The predicted molecular weight of the deduced protein was approximately 38 kDa. Blo t 1 shared 53 and 34% nucleotide and amino acid, respectively, sequence homology with Der p 1. Native Blo t 1 was detected in both crude mite and spent mite medium extracts, and its estimated molecular weight was about 26 kDa. The recombinant Blo t 1 reacted positively with IgE in 90 and 65% of sera from asthmatic children and adults, respectively, indicating that it is a major allergen. The correlation of human IgE reactivity between Blo t 1 and Der p 1 was low in these sera. The full-length cDNA encoding group 1 Blomia tropicalis mite allergen (designated as Blo t 1) has been characterized and expressed from local mites in Singapore. This fecal allergen showed high frequency of human IgE reactivity with asthmatic sera in the tropics and there was a low correlation of IgE reactivity between Blo t 1 and Der p 1.


Performance of abdominal ultrasonography in blunt trauma patients with out-of-hospital or emergency department hypotension.
We determine the test performance of abdominal ultrasonography for detecting hemoperitoneum in blunt trauma patients with out-of-hospital or emergency department (ED) hypotension. We reviewed the medical records of all blunt trauma patients hospitalized at a Level I trauma center. Patients were included if they were older than 6 years and had out-of-hospital or ED hypotension (systolic blood pressure < or =90 mm Hg) and underwent ED ultrasonography. The initial interpretation of the abdominal ultrasonography was recorded, including the presence or absence of intraperitoneal fluid and the specific location of such fluid. Presence or absence of intra-abdominal injury was determined by abdominal computed tomography scan, laparotomy, or clinical follow-up. Four hundred forty-seven patients with a mean age of 36.0+/-17.5 years were enrolled. One hundred forty-eight (33%) patients had intra-abdominal injuries, and 116 (78%) of these patients had hemoperitoneum. Abdominal ultrasonography had the following test performance for detecting patients with intra-abdominal injury and hemoperitoneum: sensitivity 92/116 (79%; 95% confidence interval [CI] 71% to 86%), specificity 316/331 (95%; 95% CI 93% to 97%), positive predictive value 92/107 (86%; 95% CI 78% to 92%), and negative predictive value 316/340 (93%; 95% CI 90% to 95%). The positive likelihood ratio was 15.8, and the negative likelihood ratio was 0.22. One hundred five (91%) of the 116 patients with intra-abdominal injuries and hemoperitoneum underwent a therapeutic laparotomy. Abdominal ultrasonography demonstrated intraperitoneal fluid in 87 (sensitivity 83%; 95% CI 74% to 90%) of these 105 patients. Of patients with out-of-hospital or ED hypotension, abdominal ultrasonography identifies most patients with hemoperitoneum and intra-abdominal injuries. Hypotensive patients with negative abdominal ultrasonography results, however, must be further evaluated for sources of their hypotension, including additional abdominal evaluation, once they are hemodynamically stabilized.


Lymphoproliferative disease after renal transplantation in Australia and New Zealand.
Lymphoproliferative disease is a common and serious complication of organ transplantation. It is well documented that the risk of its development increases with the level of immunosuppression. Less is known about its incidence, prevalence, timing, and prognosis. The authors conducted a retrospective review of all patients with lymphoproliferative disease after renal transplantation documented in the Australia and New Zealand Dialysis and Transplant Registry from 1970 to March 2003. One hundred ninety-seven cases of lymphoproliferative disease occurred in 15,930 allografts in 13,516 recipients. There has been a steady increase in its incidence and prevalence each decade since 1970. Cases cluster into an early group (<2 years after transplantation) and a late group (5-10 years after transplantation). Risk factors include exposure to a calcineurin inhibitor, but there was no increased risk in those treated with anti-T-lymphocyte antibodies. Patient survival was poor: 51% at 1 year and 39% at 5 years. Lymphoproliferative disease is an increasingly common problem after renal transplantation, and the outcome is poor. Measures to reduce its incidence might include reduction of long-term immunosuppression exposure. Established disease has a high short-term mortality, and new treatment options, such as anti-B-lymphocyte monoclonal antibodies, should be aggressively pursued.


The importance of binding kinetics and drug-target residence time in pharmacology.
A dominant assumption in pharmacology throughout the 20th century has been that in vivo target occupancy-and attendant pharmacodynamics-depends on the systemic concentration of drug relative to the equilibrium dissociation constant for the drug-target complex. In turn, the duration of pharmacodynamics is temporally linked to the systemic pharmacokinetics of the drug. Yet, there are many examples of drugs for which pharmacodynamic effect endures long after the systemic concentration of a drug has waned to (equilibrium) insignificant levels. To reconcile such data, the drug-target residence time model was formulated, positing that it is the lifetime (or residence time) of the binary drug-target complex, and not its equilibrium affinity per se, that determines the extent and duration of drug pharmacodynamics. Here, we review this model, its evolution over time, and its applications to natural ligand-macromolecule biology and synthetic drug-target pharmacology.


Overexpression of PRAD1 in a mantle zone lymphoma patient with a t(11;22)(q13;q11) translocation.
The PRAD1 gene identified from the chromosome band 11q13 region was previously demonstrated to be overexpressed in cell lines with t(11;14)(q13;q32) translocation and was suggested to be a candidate BCL-1 gene. We report here one case of mantle zone lymphoma with a t(11;22)(q13;q11), a variant translocation at the BCL-1 locus, having the PRAD1 overexpression. By analogy with the c-myc gene in Burkitt's lymphoma and the BCL-2 gene in follicular lymphoma, this case supports strongly the idea that the PRAD1 is the candidate BCL-1 gene.


Evaluation of clinical and genetic factors in the population pharmacokinetics of carbamazepine.
Carbamazepine can cause hypersensitivity reactions in ~10% of patients. An immunogenic effect can be produced by the electrophilic 10,11-epoxide metabolite but not by carbamazepine. Hypothetically, certain single nucleotide polymorphisms might increase the formation of immunogenic metabolites, leading ultimately to hypersensitivity reactions. This study explores the role of clinical and genetic factors in the pharmacokinetics (PK) of carbamazepine and 3 metabolites known to be chemically reactive or formed through reactive intermediates. A combination of rich and sparse PK samples were collected from healthy volunteers and epilepsy patients. All subjects were genotyped for 20 single nucleotide polymorphisms in 11 genes known to be involved in the metabolism or transport of carbamazepine and carbamazepine 10,11-epoxide. Nonlinear mixed effects modelling was used to build a population-PK model. In total, 248 observations were collected from 80 subjects. A 1-compartment PK model with first-order absorption and elimination best described the parent carbamazepine data, with a total clearance of 1.96 L/h, central distribution volume of 164 L and absorption rate constant of 0.45 h-1 . Total daily dose and coadministration of phenytoin were significant covariates for total clearance of carbamazepine. EPHX1-416G/G genotype was a significant covariate for the clearance of carbamazepine 10,11-epoxide. Our data indicate that carbamazepine clearance was affected by total dose and phenytoin coadministration, but not by genetic factors, while carbamazepine 10,11-epoxide clearance was affected by a variant in the microsomal epoxide hydrolase gene. A much larger sample size would be required to fully evaluate the role of genetic variation in carbamazepine pharmacokinetics, and thereby predisposition to carbamazepine hypersensitivity.


Evidence that dysregulated DNA mismatch repair characterizes human nonmelanoma skin cancer.
In addition to an established role in the repair of postreplicative DNA errors, DNA mismatch repair (MMR) proteins also contribute to cellular responses to exogenous DNA damage. Previously, we have shown that Msh2-null mice display increased sensitivity to ultraviolet (UV) B-induced tumorigenesis, but squamous cell carcinomas (SCC) generated are microsatellite stable, suggesting a role for MMR other than postreplicative repair in UV-induced cutaneous tumour formation. We questioned whether there was evidence of MMR dysfunction in human SCC, thus validating the mouse models of MMR-dependent UVB-induced skin cancer. Using tissue microarrays we examined both nuclear and cytoplasmic levels of MMR proteins MSH2, MSH6, MSH3, MLH1 and PMS2 in more than 200 cases of cutaneous SCC and basal cell carcinoma (BCC). We found that subsets of these 10 MMR protein measures were increased in nonmelanoma skin cancer (NMSC) compared with normal epidermal samples; this was particularly true of SCC. In fact, based on post hoc tests and MMR protein distribution patterns, BCC was distinct from SCC. With the exception of nuclear MSH2, the BCC had lower levels of identified MMR protein measures than SCC. We believe this to be important because not only is SCC more aggressive than BCC, but evidence suggests that these two NMSC subtypes arise through different molecular pathways. In combination with previously established roles for MMR proteins in response to UVB-induced DNA damage, our data point towards an expanded perspective of the importance of MMR proteins in the suppression of UVB-induced tumorigenesis and, potentially, tumour behaviour.


Raman Spectroscopy and Machine Learning for Agricultural Applications: Chemometric Assessment of Spectroscopic Signatures of Plants as the Essential Step Toward Digital Farming.
A growing body of evidence suggests that Raman spectroscopy (RS) can be used for diagnostics of plant biotic and abiotic stresses. RS can be also utilized for identification of plant species and their varieties, as well as assessment of the nutritional content and commercial values of seeds. The power of RS in such cases to a large extent depends on chemometric analyses of spectra. In this work, we critically discuss three major approaches that can be used for advanced analyses of spectroscopic data: summary statistics, statistical testing and chemometric classification. On the example of Raman spectra collected from roses, we demonstrate the outcomes and the potential of all three types of spectral analyses. We anticipate that our findings will help to design the most optimal spectral processing and preprocessing that is required to achieved the desired results. We also expect that reported collection of results will be useful to all researchers who work on spectroscopic analyses of plant specimens.


Use of drift substrates to characterize marine fungal communities from the west coast of Portugal.
This survey reports the occurrence, diversity and similarity of marine fungi associated with five categories of drift substrates (Arundo donax, Phragmites australis, Spartina maritima, "other stems" and driftwood) collected on four sandy beaches of the western coast of Portugal. "Other stems" and driftwood are composite samples with a variety of identified and unidentified pieces of non-woody and woody substrates respectively. Fifty-six taxa were identified, including 38 Ascomycota and 18 anamorphic fungi. Twenty-six taxa were generalists; however several cases of "substrate recurrence" were identified. The very frequent fungi differed among the categories of studied substrates, with the exception of Corollospora maritima, very frequent on four categories. Except for S. maritima, P. australis and driftwood, cases of multiple fungal colonization were rare. S. maritima was the single substrate with five different marine fungi on one sample, as well as with the highest number of very frequent fungi, highest percentage of colonization and average number of fungi per sample. Driftwood presented the highest value of fungal richness (37 taxa) and A. donax the lowest (22 taxa). ANOSIM analysis of similarity showed that all substrates supported different fungal communities with the exception of the pair P. australis/"other stems". The effect of sample size on estimated fungal richness was tested, and the results let us conclude that, although most of the sporadic fungi (<1% occurrence) will be detected only in a very large number of samples, 60 samples of A. donax and "other stems" and 70 samples of all the other substrates may suffice to assess their respective representative marine mycota.


Postmyocardial infarction pain and infarct extension in the coronary care unit: role of two-dimensional echocardiography.
Recent data suggest that patients who manifest extension of their acute myocardial infarct have a worse prognosis than to those who do not have this complication and, if identified early, may be candidates for more aggressive intervention. Serial two-dimensional echocardiography was used to diagnose myocardial infarct extension in 33 consecutive patients and its sensitivity was compared with that of electrocardiography (ECG) and serum creatine kinase determination. Infarct extension was diagnosed clinically using ECG and enzymatic criteria. The echocardiograms were scored using a weighted regional scoring system, with each segment of the left ventricle ascribed a percent of the total left ventricular mass. Abnormal regions were summed to yield a percent asynergy. In the postinfarction period, 19 episodes of acute ischemia occurred; in 9 of these episodes clinical extension was confirmed, and in 7 of the 9 episodes echocardiographic extension was detected. In the patients in whom infarct extension was documented clinically, the mean asynergy score increased from a mean of 19.2 +/- 11.3% to 36.1 +/- 18.2% (p less than 0.01). Where no extension was detected, the asynergy score improved from the initial 31.5 +/- 24.1% to 28.3 +/- 21.9% (p less than 0.05). The extent of the change in echocardiographic wall motion abnormality was not predicted by the amount of creatine kinase reelevation. Electrocardiography alone failed to distinguish which episodes of ischemia represented infarct extension and which did not. Greater degrees of asynergy were associated with worse in-hospital mortality. Two-dimensional echocardiography is a useful method for detecting myocardial infarct extension providing a means of assessing functional impact and prognosis.


The Q192R polymorphism of the paraoxonase 1 gene is a risk factor for coronary artery disease in Saudi subjects.
Paraoxonase-1 (PON1) is a HDL-bound antioxidant enzyme that protects LDL from oxidative modification. Discovery of the antioxidant properties of PON1 led to extensive research on its role in the initiation and progression of atherosclerosis. The Q192R (rs662; A/G) polymorphism, which results in the glutamine to arginine substitution at position 192, of the PON1 gene has been linked to increased atherosclerosis risk in several but not all population studies. Besides genetic factors, environmental variables and ethnicity have been implicated as factors responsible for the ambiguity in relating the PON1 gene with atherosclerotic risk. Here, we tested the association of the Q192R polymorphism with coronary artery disease (CAD) in Saudi ethnic subjects taking environmental factors into consideration. The genomic DNA samples from 121 angiographically confirmed CAD cases and 108 normal healthy control subjects were genotyped by PCR-RFLP analysis. The distribution of QQ, QR, and RR genotypes was significantly different between cases and controls (p < 0.005). The RR genotype was associated with CAD risk independently of several established risk factors including age, gender, smoking, obesity, and diabetes (OR 2.2, 1.4-7.4, p < 0.01). Genotype-based stratification of demographic and biochemical data revealed that the RR genotype has proatherogenic properties. This study, thus, identifies the Q192R polymorphism as an additional risk factor for CAD in the Saudi population and suggests that it may have prognostic value. The negative effect of this genetic variant is presumably due to the diminished ability of the RR variant genotype of PON1 to blunt LDL oxidation.


Posttraumatic symptom profiles among adult survivors of childhood sexual abuse: A longitudinal study.
In the present study, our aim was to examine longitudinal posttraumatic stress symptom (PTSS) trajectories in a Norwegian sample of adults who had experienced sexual abuse during childhood, and to identify predictors of PTSS-trajectory belongingness. The sample consisted of 138 adult survivors of childhood sexual abuse (96.4% women, mean age=42.9years, mean age at the first abuse=5.9 years), recruited from support centers for sexual abuse survivors. The majority (78.3%) reported penetrative abuse, and a large proportion of the sample reported that the perpetrator was a biological parent (38.4%) or someone they trusted (76.1%), reflecting a high severity level of the abusive experiences. Latent Profile Analyses revealed the best overall fit for a two PTSS-trajectories model; one trajectory characterized by sub-clinical and decreasing level of PTSS (54.9%), and the other by high and slightly decreasing level of PTSS (45.1%). Increased odds for belonging to the trajectory with clinical level symptoms was found among those who reported higher levels of exposure to other types of childhood maltreatment (OR=3.69, p=0.002), sexual abuse enforced by physical violence (OR=3.04, p=0.003) or threats (OR=2.56, p=0.014), very painful sexual abuse (OR=2.73, p=0.007), or who had experienced intense anxiety, helplessness or fear during the abuse (OR=2.97, p=0.044). Those in the trajectory with clinical level PTSS reported lower levels of perceived social support and more relational difficulties compared to those in the sub-clinical PTSS trajectory. In conclusion, different longitudinal PTSS trajectories can be found among adult survivors of childhood sexual abuse. Significant predictors of PTSS-trajectory belongingness are discussed alongside their potential implications for preventive efforts and clinical interventions.


Fostering critical thinking skills: a strategy for enhancing evidence based wellness care.
Chiropractic has traditionally regarded itself a wellness profession. As wellness care is postulated to play a central role in the future growth of chiropractic, the development of a wellness ethos acceptable within conventional health care is desirable. This paper describes a unit which prepares chiropractic students for the role of "wellness coaches". Emphasis is placed on providing students with exercises in critical thinking in an effort to prepare them for the challenge of interfacing with an increasingly evidence based health care system. This case study describes how health may be promoted and disease prevented through development of personalized wellness programs. As critical thinking is essential to the provision of evidence based wellness care, diverse learning opportunities for developing and refining critical thinking skills have been created. Three of the learning opportunities are an intrinsic component of the subject and, taken together, contributed over 50% of the final grade of the unit. They include a literature review, developing a client wellness contract and peer evaluation. In addition to these 3 compulsory exercises, students were also given an opportunity to develop their critical appraisal skills by undertaking voluntary self- and unit evaluation. Several opportunities for informal self-appraisal were offered in a structured self-study guide, while unit appraisal was undertaken by means of a questionnaire and group discussion at which the Head of School was present. Formal assessment showed all students capable of preparing a wellness program consistent with current thinking in contemporary health care. The small group of students who appraised the unit seemed to value the diversity of learning experiences provided. Opportunities for voluntary unit and self-appraisal were used to varying degrees. Unit evaluation provided useful feedback that led to substantial changes in unit structure. Students have demonstrated themselves capable of applying critical thinking in construction of evidence based wellness programs. With respect to unit design, selective use of learning opportunities highlighted the desirability of using obligatory learning opportunities to ensure exposure to core constructs while student feedback was found to provide useful information for enriching unit review. It is hoped inclusion of critical thinking learning opportunities in the undergraduate chiropractic curriculum will contribute to the development of an evidence based ethos in chiropractic care.


Multivariate determination of 13CO2/12CO2 ratios in exhaled mouse breath with mid-infrared hollow waveguide gas sensors.
The (12)CO2/(13)CO2 isotope ratio is a well-known marker in breath for a variety of biochemical processes and enables monitoring, e.g., of the glucose metabolism during sepsis. Using animal models-here, at a mouse intensive care unit-the simultaneous determination of (12)CO2 and (13)CO2 within small volumes of mouse breath was enabled by coupling a novel low-volume hollow waveguide gas cell to a compact Fourier transform infrared spectrometer combined with multivariate data evaluation based on partial least squares regression along with optimized data preprocessing routines.


Adenosine 5'-monophosphate enhances the dark and isoproterenol-induced rise in rat pineal N-acetyltransferase activity.
Exposure of rats to light during darkness or blockade of the pineal beta-adrenoceptor in stimulated pineal glands results in a rapid fall in pineal N-acetyltransferase (NAT) activity. Maintenance of a high level of NAT activity requires continuous stimulation of the pineal beta-adrenoceptors. It is not known what factors in the pinealocyte are responsible for this rapid inactivation of NAT activity. In the present study we have attempted to investigate a possible regulatory role of 5'-AMP on pineal NAT activity. The results show that 5'-AMP further enhances dark-induced as well as isoproterenol-induced NAT activity by approximately 3-fold but does not alter unstimulated daytime NAT activity. Theophylline, an inhibitor of 5'-AMP synthesis, when administered early in the dark phase, caused a rise in pineal cAMP with a concomitant fall in pineal NAT activity. These findings indicate that 5'-AMP could play a role in the activation of pineal NAT. The possibility that the rapid inactivation of NAT is due to a rapid removal of 5'-AMP by, for example, phosphorylation, remains to be investigated.


Serum stress responsive gene EhslncRNA of Entamoeba histolytica is a novel long noncoding RNA.
Non coding RNAs are known to play important roles in regulating gene expression at the transcriptional and posttranscriptional levels in metazoans. There is very little information available about non coding RNAs in protists such as Entamoeba histolytica. Antisense and micro RNAs have been reported in E. histolytica, however no long non coding RNAs has been reported yet. Here, we report our findings on an in vitro serum stress-inducible gene EhslncRNA, a member of B1 transmembrane kinase family of E. histolytica. EhslncRNA encodes a transcript of 2.6 kb and sequence analysis revealed that there is no ORF >150 bp within this transcript. The transcript was found to be polyadenylated and mainly associated with monosomes in the cytoplasm under serum starvation. In normal proliferating cells this RNA is mainly present in the nucleus. The promoter element was mapped between 437 to 346 nucleotides upstream of transcriptional start site and has both positive and negative regulatory elements. Deletion of the negative element converted the promoter to serum inducible type. Oxygen and heat stress also increased expression levels of EhslncRNA. These observations suggest that EhslncRNA may be a long non coding RNA and likely to help cells withstand stressful conditions in the host.


Angiosarcoma after breast-conserving therapy: experience with hyperfractionated radiotherapy.
To report our promising results of hyperfractionated radiotherapy (RT) in conjunction with surgery for angiosarcoma occurring after breast-conserving therapy for early-stage breast cancer. Since 1997, 3 cases of angiosarcoma after breast-conserving therapy have been managed at the University of Florida. The histologic specimens in each case were reviewed and graded by one of us (J.D.R.). Explosive growth of discolored skin lesions coincident with histologic evidence of angiosarcoma characterized all 3 cases but was preceded by a fairly indolent period (almost 2 years) of atypical vascular hyperplasia in 2 patients. All 3 patients were treated initially with radical surgery for the angiosarcoma, but extensive recurrences were noted within 1 to 2 months of surgery. Because of the extremely rapid growth noted before and after surgery, hyperfractionated RT was used. Two of the patients underwent planned resection after RT, and neither specimen demonstrated any evidence of high-grade angiosarcoma. All 3 patients were alive without any recurrent disease 22, 38, and 39 months after treatment. Hyperfractionated irradiation appears to be effective treatment for rapidly proliferating angiosarcoma. For previously untreated angiosarcoma, we now recommend hyperfractionated RT followed by surgery to enhance disease control and remove as much reirradiated tissue as possible.


[Risk factors for non communicable chronic diseases among workers of a financial company].
The epidemic of cardiovascular diseases in Chile, requires the development of strategies in health promotion and prevention. To assess the prevalence of risk factors for chronic non communicable diseases among workers of a financial company in Metropolitan Santiago. Assessment of 2,225 workers (1,383 males with a median age of 49 years and 842 females with a median age of 43 years). All answered an enquiry about education, medical history, smoking habits and physical activity. Body mass index and blood pressure were measured and a blood sample was obtained to measure blood glucose and lipid levels. Logistic repression models were used to determine the main risk factors for hypertension, diabetes, obesity, hypercholesterolemia and hyperuricemia. Sixteen percent of studied subjects were obese, 49% had overweight, 57% had hypercholesterolemia, 28% had high blood pressure, 4% were diabetic, 4% had hyperuricemia, 45% smoked and 83% were sedentary. Each worker had a mean of 2.4+/-1.1 risk factors. This figure was significantly higher among men, obese subjects, those older than 40 years and those with a lower educational level. There is an important disease burden among the studied subjects, specially among obese and older individuals. Healthy lifestyles should be promoted in this population.


The anti-inflammatory activities of ethanol extract from Dan-Lou prescription in vivo and in vitro.
Although, Dan-Lou prescription (DLP) is used for antagonizing check discomfort and heartache, the pharmacological mechanism has not been clearly illustrated. Our present study aimed to design inflammatory models induced by LPS in vivo and in vitro to investigate the anti-inflammation of DLP ethanol extract (EEDL) and the potential mechanisms. EEDL was prepared and then analyzed by high performance liquid chromatography (HPLC). Further, the anti-inflammatory effects of EEDL in vivo was evaluated by measuring inflammation-associated factors includingcytokines, chemokines and acute phase proteins in lipopolysaccharide (LPS)-induced mice serum and liver. The anti-inflammatory mechanism exploration of EEDL was performed in LPS-stimulated RAW 264.7 cells. Different effects of EEDL on nitric oxide (NO) and prostaglandin (PG)E2 secretion were investigated by Griess reagent method and enzyme-linked immunosorbent assay (ELISA) respectively. Then the mRNA and protein expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 were measured by real-time reverse-transcription polymerase chain reaction (RT-PCR), ELISA and Western blot. Other chemokines and acute phase proteins were determined by proteome profile array. Finally, the ELISA based transcription factor assay was applied to measure the DNA-binding activity of nuclear transcription factor (NF)-κB p65. Eight compounds from EEDL have been identified as gallic acid, salvianic acid, puerarin, daidzin, paeoniflorin, salvianolic acid B, cryptotanshinone, and tanshinone IIA, with amounts of 0.26, 9.84, 10.41, 2.55, 9.44, 3.82, 0.24 and 0.3 mg/kg, respectively. In vivo, EEDL administration antagonized the up-regulation of more than 17 kinds of cytokines, chemokines and acute phase proteins in LPS-treated mice serum, and inhibited LPS-induced IL-6 mRNA and protein expression in mice liver tissue. In vitro, LPS-induced NO and PGE2 over-productions were decreased by EEDL treatment. The mRNA and protein expression of iNOS, COX-2 and IL-6 were similarly inhibited by EEDL treatment, which might be attributed to decrease the DNA-binding activity of NF-κB p65. EEDL was valid for anti-inflammation and the potential molecular mechanisms might be due to the inhibition of of LPS-induced iNOS/NO, COX-2/PGE2 and cytokines expression by antagonizing the activation of NF-κB p65.


Terrestrial vertebrates have two keratin gene clusters; striking differences in teleost fish.
Keratins I and II form the largest subgroups of mammalian intermediate filament (IF) proteins and account as obligatory heteropolymers for the keratin filaments of epithelia. All human type I genes except for the K18 gene are clustered on chromosome 17q21, while all type II genes form a cluster on chromosome 12q13, that ends with the type I gene K18. Highly related keratin gene clusters are found in rat and mouse. Since fish seem to lack a keratin II cluster we screened the recently established draft genomes of a bird (chicken) and an amphibian (Xenopus). The results show that keratin I and II gene clusters are a feature of all terrestrial vertebrates. Because hair with its multiple hair keratins and inner root sheath keratins is a mammalian acquisition, the keratin gene clusters of chicken and Xenopus tropicalis have only about half the number of genes found in mammals. Within the type I clusters all genes have the same orientation. In type II clusters there is a rare gene of opposite orientation. Finally we show that the genes for keratins 8 and 18, which are the first expression pair in embryology, are not only adjacent in mammals, but also in Xenopus and three different fish. Thus neighboring K8 and K18 genes seem a feature shared by all vertebrates. In contrast to the two well defined keratin gene clusters of terrestrial vertebrates, three teleost fish show an excess of type I over type II genes, the lack of a keratin type II gene cluster and a striking dispersal of type I genes, that are probably the result of the teleost-specific whole genome duplication followed by a massive gene loss. This raises the question whether keratin gene clusters extend beyond the ancestral bony vertebrate to cartilage fish and lamprey. We also analyzed the complement of non-keratin IF genes of the chicken. Surprisingly, an additional nuclear lamin gene, previously overlooked by cDNA cloning, is documented on chromosome 10. The two splice variants closely resemble the lamin LIII a + b of amphibia and fish. This lamin gene is lost on the mammalian lineage.


Radiographic signs of gastrointestinal perforation in children: A pictorial review.
Plain abdominal radiographs remain an important aid for clinicians in the diagnosis of gastrointestinal perforation, especially in neonates and very sick children where clinical features of peritonitis may not be as prominent. Suggestive radiographic features are not always very obvious, especially when taken in the supine position and may lead to delayed or missed diagnosis. Through a pictorial review of plain radiographs, this article highlights a number of documented features of gastrointestinal perforation on X-ray in the paediatric setting, which increases the accuracy of diagnosis.


Surgical management of cystic lesions in the liver.
Liver cysts are common, occurring in up to 5% of the population. For many types of cysts, a variety of different treatment options exist and the preferred management is unclear. A Pubmed and Medline literature review using key words non-parasitic hepatic cysts, polycystic liver disease, echinococcus, hydatid cysts parasitic cysts, Caroli's disease, cystadenoma; liver abscess, surgery, aspiration and treatment was undertaken and papers pertaining to the diagnosis and management of cystic lesions within the liver were retrieved. Asymptomatic simple cysts in the liver require no treatment. Therapy for symptomatic cysts may incorporate aspiration with sclerotherapy or de-roofing. At present, insufficient evidence exists to recommend one over the other. Polycystic liver disease presents a unique management problem because of high morbidity and mortality rates from intervention and high rates of recurrence. Careful patient counselling and assessment of symptom index is essential before embarking on any treatment. New medical treatments may ameliorate symptoms. Acquired cystic lesions in the liver require a thorough work-up to fully characterize the abnormality and direct appropriate treatment. Hydatid cysts are best treated by chemotherapy followed by some form of surgical intervention (either aspiration and sclerotherapy or surgery). Liver abscesses can effectively be treated by aspiration or drainage. With improved antimicrobial efficacy, prolonged treatment with antibiotics may also be considered. All patients with cystic lesions in the liver require discussion at multi-disciplinary meetings to confirm and the diagnosis and determine the most appropriate method of treatment.


IL-2 therapy in type 1 diabetes: "Trials" and tribulations.
IL-2 facilitates immunity or tolerance depending on its availability. In model systems, it is well established that low dose IL-2 promotes selective expansion of regulatory T cells (Treg), an IL-2 responsive cell type known to control autoimmunity. Moreover, many autoimmune diseases are marked by defects in Treg and/or IL-2/IL-2 receptor signaling. Thus, patients with immune-mediated diseases were treated with IL-2 with the goal of increasing Treg and controlling autoimmunity. In graft versus host disease, HCV-induced vasculitis and type 1 diabetes (T1D), Treg numbers increased with IL-2 therapy. Yet there was no relationship between Treg number and clinical outcome. In fact, in T1D subjects treated with rapamycin and IL-2 therapy there was no measureable clinical benefit. In this review, we compare results from IL-2 treatment of patients with immune-mediated diseases, discuss possible mechanisms of IL-2 treatment and suggest future directions for use of IL-2 therapy in T1D.


A nationwide epidemiological study of mental disorders in Korea.
Epidemiological studies in Korea on mental illness began about four decades ago by Choi and Yoo. This was followed by more than 25 papers. Interviews by psychiatrists were not randomly selected samples. Consistent diagnostic tools were not used except by Yeon et al. The definition of prevalence was not definite and, therefore, not comparable. The research was confined to major psychoses such as schizophrenia, manic depressive illnesses, mental retardation and epilepsy. Most of the studies were performed in rural areas only. The present study was designed to meet the above described criteria as well as testing the applicability of Diagnostic Interview Schedule-III (DIS-III) in Korea. In order to accomplish those goals the Korean version of DIS-III was constructed and the lifetime prevalence of mental disorders was studied both in urban (Seoul) and rural areas.


The wrapping phenomenon in air-dried and negatively stained preparations.
We demonstrate that the interface energies involved in the direct preparation of supramolecular structures onto supporting films leads very frequently to a smooth wrapping of the supporting film around approximately one third to one half of the structure. We conclude that in such cases the structure is more rigid than the supporting film; examples being ribosomes, small viruses and small glass fragments. Other structures are less rigid and become significantly flattened. Complete flattening is frequently observed with empty virus capsids. The sandwich technique, by which a specimen is placed between two supporting films, in general leads to increased flattening. Only in few cases (e.g. ribosomes) are biological particles rigid enough to resist flattening and become wrapped from both sides.


Depth-dependent proton magnetization transfer in articular cartilage.
To measure the proton magnetization transfer ratio (MTR) maps in control and collagen-depleted bovine patellar cartilage specimens as a function of cartilage depth during mechanical compression. One-dimensional proton projection MR images employing a spin-echo imaging sequence were obtained on a custom-built NMR spectrometer interfaced to an Oxford magnet operating at 2T. The mechanical compressions were performed with a custom-built MR-compatible pressure cell and evaluated dynamically via one-dimensional projection. High-spatial-resolution two-dimensional MT images were obtained using a fast spin-echo (FSE) sequence on a 4T whole-body GE Signa scanner (GEMS, Milwaukee, WI, USA) to quantify the MTR maps of normal and collagen-depleted bovine patellae. All of the cartilage plugs from the bovine patellae showed that the MTR value increases continuously as a function of cartilage depth. Although the overall MTR trend as a function of depth is the same in both control and collagen-depleted cartilage, the magnitude of the MTR value differs between the two. The MTR value is decreased with collagen depletion and increased with mechanical compression. The increase in MTR value during compression may be due to a decrease in free water content and volume, resulting in an increase in collagen concentration. We demonstrated that the MTR in bovine patellar cartilage is depth-dependent and is relatively higher in the radial zone compared to the superficial zone. The high MTR in the radial zone not only depends on collagen content, it may also reflect a number of other parameters, such as the arrangement of macromolecules, high solid content, bound water fraction attached to macromolecules, radial orientation, etc.


Vagus nerve stimulation (VNS) is effective in a rat model of antidepressant action.
Depression is a common but debilitating illness that afflicts a large population and costs the US economy a staggering $40 billion dollars per year. Clinical studies have demonstrated that vagus nerve stimulation (VNS) is an effective treatment for medication-resistant depression. Understanding VNS's antidepressant mechanisms is key to improving the therapy and selecting the best surgical candidates, and demonstration that VNS is effective in a validated test of antidepressant activity allows us to elucidate these mechanisms in a cost-effective manner. In the present study, Wistar Kyoto rats were implanted with a cuff electrode on the left cervical vagus nerve. The next day, they were placed into a water-filled Plexiglas cylinder for 15 min. After this forced-swim session, one of three treatment conditions were administered over 4 consecutive days: 30 min per day of continuous VNS, 10 mg/kg of desipramine twice per day, or three daily electroconvulsive shocks (ECS). Yoked controls underwent sham procedures, but received no treatment. On the fourth day, the rats were given a 5-min, videotaped swim test. A blinded observer used the videotape to calculate the percentage of time that the rats were immobile (an index of depression) during the swim test. VNS significantly reduced immobility time as compared to unstimulated controls, indicating good antidepressant efficacy. This reduction did not differ statistically from that obtained from rats treated with either desipramine or ECS, two standard antidepressant treatments. These results indicate that VNS is an effective antidepressant in the forced-swim test, allowing us to now investigate possible therapeutic mechanisms.


Building a meta-predictor for MHC class II-binding peptides.
Prediction of class II major histocompatibility complex (MHC)-peptide binding is a challenging task due to variable length of binding peptides. Different computational methods have been developed; however, each has its own strength and weakness. In order to provide reliable prediction, it is important to design a system that enables the integration of outcomes from various predictors. In this chapter, the procedure of building such a meta-predictor based on Naïve Bayesian approach is introduced. The system is designed in such a way that results obtained from any number of individual predictors can be easily incorporated. This meta-predictor is expected to give users more confidence in the prediction.


Hibernoma: a possible model of brown fat histogenesis.
Hibernomas are composed of cells remarkably similar to those observed in brown adipose tissue. A surgically resected hibernoma was observed to contain cells at all stages of maturation from immature, relatively lipid free cells to multiloculated and finally uniloculated adipocytes. The ultrastructural features of adipocytes contained in the hibernoma were compared to previously reported features of differentiating preadipocytes and lipid depleted mature adipocytes derived from human white adipose tissue. This comparison confirmed the existence of distinct mitochondrial and cytoplasmic membrane component differences at all developmental stages and suggests that brown and white adipose tissue are two unique histologic types.


The effect of warfarin on urine calcium oxalate crystal growth inhibition and urinary excretion of calcium and nephrocalcin.
Urine contains inhibitors of calcium oxalate (CaOx) crystal growth. One such inhibitor is nephrocalcin (NC), a glycoprotein which is made in the kidney and contains several residues of gamma-carboxyglutamic acid (Gla) per molecule. The presence of Gla may be important to its ability to inhibit crystal growth. Several studies suggest that vitamin K-dependent proteins may also play a role in renal calcium (Ca) handling, and that vitamin D deficiency may lead to excess urinary Ca loss, but the effect of the vitamin K antagonist warfarin on urinary Ca excretion and CaOx growth inhibition in humans is not known. We studied 11 men while they were taking warfarin for a mean of 252 days, and again a mean of 64 days after its discontinuation. Urinary Ca excretion did not differ between those on or off warfarin, or between those on warfarin and normal controls. The ability of the subjects' urine to inhibit CaOx crystal growth did not differ on or off warfarin, or from that of control urine, and the excretion of immunoreactive NC also did not differ between these groups. NC was found to be responsible for approximately 16% of the CaOx growth inhibition seen. These results do not suggest that vitamin K-dependent proteins play a major role in renal Ca excretion in men, or that interference with vitamin K alters NC excretion or inhibitory activity of the urine.


Clinical challenges of glycemic control in the intensive care unit: A narrative review.
Glucose control in patient admitted to the intensive care unit has been a topic of much debate over the past 20 years. The harmful effects of uncontrolled hyperglycemia and hypoglycemia in critically ill patients is well established. Although a large clinical trial in 2001 demonstrated significant mortality and morbidity benefits with tight glucose control in this patient population, the results could not be replicated by other investigators. The "Normoglycemia in Intensive Care Evaluation-Survival Using Glucose Algorithm Regulation" trial in 2009 established that tight glucose control was not only of no benefit, but in fact harmful due to the significant risk of hypoglycemia. The current guidelines suggest a moderate approach with the initiation of intravenous insulin therapy in critically ill patients when the blood glucose level is above 180 mg/dL. The most important factor that underpins glycemic management in intensive care unit patients is the consequent prevention of hypoglycemia. Robust glucose monitoring strategies and insulin protocols need to be implemented in order to achieve this goal.


Dyscusins A-C, three new steroids from the leaves of Dysoxylum cumingianum.
Three new steroids dyscusins A-C (1-3), including a stigmastane-type sterol and two pregnanes, together with two known steroids were isolated from the leaves of Dysoxylum cumingianum (Meliaceae). Their structures were elucidated on the basis of extensive spectroscopic analyses. In a cytotoxicity assay, compound 1 showed ten-fold enhanced cytotoxicity against multi-drug resistant cancer cells (KB-C2) in the presence of 2.5 µM colchicine as compared with the absence of colchicine. This notable finding indicated that 1 possessed a multi-drug resistant reversal effect.


A versatile and simple method for staining nervous tissue using Giemsa dye.
A method for staining nervous tissue with Giemsa dye is described. The procedure is easy to perform and works well on paraffin, celloidin and frozen sections. The results combine the properties of the Nissl stains with the polychromatism of the Romanowsky dyes. The method also provides good results for counterstaining autoradiographies, or when applied after horseradish or peroxidase-antiperoxidase techniques. In the latter case, Giemsa dye darkens the immunoreactive product in the same manner as osmium tetroxide but avoids the well-known risks of handling this toxic agent.


Childhood temperament and family environment as predictors of internalizing and externalizing trajectories from ages 5 to 17.
Childhood temperament and family environment have been shown to predict internalizing and externalizing behavior; however, less is known about how temperament and family environment interact to predict changes in problem behavior. We conducted latent growth curve modeling on a sample assessed at ages 5, 7, 10, 14, and 17 (N = 337). Externalizing behavior decreased over time for both sexes, and internalizing behavior increased over time for girls only. Two childhood variables (fear/shyness and maternal depression) predicted boys' and girls' age-17 internalizing behavior, harsh discipline uniquely predicted boys' age-17 internalizing behavior, and maternal depression and lower family income uniquely predicted increases in girls' internalizing behavior. For externalizing behavior, an array of temperament, family environment, and Temperament x Family Environment variables predicted age-17 behavior for both sexes. Sex differences were present in the prediction of externalizing slopes, with maternal depression predicting increases in boys' externalizing behavior only when impulsivity was low, and harsh discipline predicting increases in girls' externalizing behavior only when impulsivity was high or when fear/shyness was low.


A compact Z-scheme heterojunction of BiOCl/Bi2WO6 for efficiently photocatalytic degradation of gaseous toluene.
Construction of Z-scheme heterojunction photocatalysts with efficient electron-hole pairs separation and robust oxidation abilities is a promising strategy to decompose volatile organic compounds (VOCs). Herein, UV-light-driven BiOCl and visible-light-driven Bi2WO6 were successfully combined via a one-pot hydrothermal method and compact Z-scheme heterojunction photocatalyst BiOCl/Bi2WO6 was obtained. Owing to the similar precursors and synthesis conditions, the integrated BiOCl/Bi2WO6 heterojunction was intimate and homogenous, which resulted in the efficient separation of photogenerated carriers, and generated abundant holes (h+), hydroxyl radicals (·OH) and superoxide radicals (·O2-). The optimal BiOCl/Bi2WO6 photocatalyst (BWOCl-2), achieved by tailoring the amount of hydrochloric acid, exhibited almost 100 % of toluene degradation and excellent durability. Electron spin resonance (ESR) results revealed that h+, ·O2- and ·OH were dominant active species in the BiOCl/Bi2WO6 photocatalytic system. The degradation intermediate products were monitored by in situ Diffuse Reflection Infrared Fourier Transform spectroscopy (DRIFTS) and the possible photocatalytic mechanism was also revealed according to the band structure of BiOCl/Bi2WO6 heterojunction. This work provided a novel avenue to design an efficient homogenous heterojunction photocatalyst for the efficient degradation of VOCs under sunlight.


Temporization techniques in fixed prosthodontics.
Temporary restorations are very important during the construction of final restorations. The success of the final restoration often depends on a well-made temporary. This article reviews the requirements, materials, and techniques available to the profession for temporary restorations.


Measurement of 13 C turnover into glutamate and glutamine pools in brain tumor patients.
Malignant brain tumors are known to utilize acetate as an alternate carbon source in the citric acid cycle for their bioenergetics. 13 C NMR-based isotopomer analysis has been used to measure turnover of 13 C-acetate carbons into glutamate and glutamine pools in tumors. Plasma from the patients infused with [1,2-13 C]acetate further revealed the presence of 13 C isotopomers of glutamine, glucose, and lactate in the circulation that were generated due to metabolism of [1,2-13 C]acetate by peripheral organs. In the tumor cells, [4-13 C] and [3,4-13 C]glutamate and glutamine isotopomers were generated from blood-borne 13 C-labeled glucose and lactate which were formed due to [1,2-13 C[acetate metabolism of peripheral tissues. [4,5-13 C] and [3,4,5-13 C]glutamate and glutamine isotopomers were produced from [1,2-13 C]acetyl-CoA that was derived from direct oxidation of [1,2-13 C] acetate in the tumor. Major portion of C4 13 C fractional enrichment of glutamate (93.3 ± 0.02%) and glutamine (90.9 ± 0.03%) were derived from [1,2-13 C]acetate-derived acetyl-CoA.


Novel method of monitoring electroencephalography at the site of microdialysis during chemically evoked seizures in a freely moving animal.
This paper covers the design, development and operation of a novel piece of equipment, based around the CMA/12 guide probe (Carnegie Medicin, Sweden), which offers a low cost alternative for monitoring EEG at the site of microdialysis in a freely moving animal. This equipment is entirely based on commercially available parts, and thus can be easily replicated. Moreover, it is less intrusive than earlier models, offering advantages for experiments in which behavioural testing or chronic monitoring is required. We illustrate its use in a study of changes in electrical seizure activity, in both cortex and basal nuclei, evoked by the administration of the chemoconvulsant soman. The inference from the many experimental paradigms looking at the mechanisms of chemoconvulsants is that paroxysmal discharges are a better correlate of seizure activity than behavioural signs. The correlation of the EEG with extracellular neurotransmitter data, over a period of hours post-injection of chemoconvulsant, allows the determination of whether extracellular neurotransmitter changes are a cause or consequence of the evoked electrical activity.


Octatropine-methyl-bromide and sulglycotide salt in the short-term treatment of active duodenal ulcer. A double blind endoscopic study of 40 outpatients.
Forty outpatients with endoscopically confirmed duodenal ulcers were entered in a double blind trial. They were randomly allocated to octatropine-methyl-bromide and sulglycotide salt (GVP) or placebo. The results show that the combination of the two drugs is less efficacious than the two constituent substances taken separately, is not more efficacious than placebo in ulcer healing, and is ineffective with regard to ulcer pain.


An Analysis of Research from Faculty at U.S. Adult Reconstruction Fellowships.
We reviewed all articles published in three major orthopaedic journals from January 2010 to December 2014. Any article focusing on adult reconstruction of the hip or knee was reviewed for first and last authorship, institution, and level of evidence. Three institutions had authored work from arthroplasty faculty that fell within the top five most published institutions in all three journals, while one institution ranked first in all three journals. 43 of 67 (64.2%) reconstruction fellowships had at least one publication included in this study. The majority of the adult reconstruction literature published by faculty at U.S. reconstruction fellowships stems from a few academic centers with the ten most prolific institutions accounting for 65.9% of all U.S. fellowship publications.


Carcinoma of the gastroesophageal junction. A ten year experience with esophagogastrectomy.
Eighty-six patients with carcinoma of the gastroesophageal junction were treated between 1966 and 1976. Adenocarcinoma was present in 62 patients and squamous cell carcinoma in 24. Surgical exploration was performed on 68 patients (79%) and 52 lesions (60%) were resected by combined midline laparotomy and right thoracotomy. There were 6 deaths (11%), 2 due to anastomotic leak. The mean survival for all resected patients was 2.1 years with a 22% three year life table survival (10/52). Five of 14 patients with negative nodes are alive more than five years. Palliative resection in 17 patients resulted in a mean survival of 10.5 months and no five year survivals. Esophagogastrectomy utilizing the Lewis technic reduces operative mortality and extends survival for patients with carcinoma of the gastroesophageal junction.