A Multi-Site Evaluation of A National Employee Wellness Initiative at the Department of Veterans Affairs.
The Department of Veterans Affairs (VA) seeks to transform its health care delivery from disease-centered, episodic care to a holistic and patient-centered model known as the Whole Health System (WHS) of care. Employee engagement and buy-in are crucial to this cultural transformation. The VA aspires to provide employees with opportunities to experience whole health in their personal and professional lives through a national Employee Whole Health (EWH) program. Although there are national recommendations, different local facilities may have unique strategies and challenges as they implement this program. This study aimed to conduct a program evaluation of EWH at three different VA facilities across the United States in order to identify facilitators and barriers to the implementation of EWH. The team used the RE-AIM framework to develop an interview guide to assess various domains of implementation. Quantitative data on whole health offerings at each site were gauged using a national employee education platform. Standardized employee-related metrics at each site were assessed using the annual, national VA employee survey. EWH has had variable implementation at the three sites. Sites noted main facilitators as employee interest as well as available skills and expertise for delivering complementary and integrative care to employees. Limited staffing for EWH and a lack of dedicated employee time were cited as barriers. The infrastructure to perform local program evaluations to demonstrate effectiveness and impact were missing. Employee engagement in whole health activities has the potential to support the VA's mission to transform its health care delivery model. Currently, the use of EWH and its potential impact are difficult to discern based on available information. Local sites need guidance to conduct program evaluations and find creative solutions to enhance employee participation. A robust measurement system to demonstrate effectiveness is paramount to ensure the success of this initiative.


Pretreatment Acoustic Predictors of Gender, Femininity, and Naturalness Ratings in Individuals With Male-to-Female Gender Identity.
The purpose of this study was to describe the pretreatment acoustic characteristics of individuals with male-to-female gender identity (IMtFGI) and investigate the ability of the acoustic measures to predict ratings of gender, femininity, and vocal naturalness. This retrospective descriptive study included 2 groups of participants. Speakers were IMtFGI who had not previously received communication feminization treatment (N = 25). Listeners were members of the lay community (N = 30). Acoustic data were retrospectively obtained from pretreatment recordings, and pretreatment recordings also served as stimuli for 3 perceptual rating tasks (completed by listeners). Acoustic data generally were within normal limits for male speakers. All but 2 speakers were perceived to be male, limiting information about the relationship between acoustic measures and gender perception. Fundamental frequency (reading) significantly predicted femininity ratings (p = .000). A total of 3 stepwise regression models indicated that minimum frequency (range task), second vowel formant (sustained vowel), and shimmer percentage (sustained vowel) together significantly predicted naturalness ratings (p = .005, p = .003, and p = .002, respectively). Study aims were achieved with the exception of acoustic predictors of gender perception, which could be described for only 2 speakers. Future research should investigate measures of prosody, voice quality, and other aspects of communication as predictors of gender, femininity, and naturalness.


Kids First: A Multicomponent Onboarding for Practitioner Students in a School-Based Health Center.
School-Based Health Centers (SBHCs) often serve vulnerable populations who have been exposed to adverse childhood experiences (ACEs) which have been tied to an increase in adult health risk factors. At an urban SBHC serving adolescent students, 75% of patients reported three or more ACEs. This SBHC also had multiple practitioner students. A multicomponent onboarding was created to implement the Patient Interaction Standard of Care, addressing the SBHC model, adolescent care, and ACEs. Practitioner students that completed the onboarding demonstrated 97% adherence to the Patient Interaction Standard of Care "Always" or "Most of the Time." By onboarding frequent practitioner students, care provided to this vulnerable patient population was more consistently aligned to evidenced-based care appropriate for the SBHC model, adolescent care, and ACEs. This demonstrates the importance of mandatory onboarding completion compliance and further implementation across other SBCHs.


Neighbourhood-socioeconomic variation in women's diet: the role of nutrition environments.
Living in socioeconomically disadvantaged neighbourhoods is associated with increased risk of a poor diet; however, the mechanisms underlying associations are not well understood. This study investigated whether selected healthy and unhealthy dietary behaviours are patterned by neighbourhood-socioeconomic disadvantage, and if so, whether features of the neighbourhood-nutrition environment explain these associations. A survey was completed by 1399 women from 45 neighbourhoods of varying levels of socioeconomic disadvantage in Melbourne, Australia. Survey data on fruit, vegetable and fast-food consumption were linked with data on food store locations (supermarket, greengrocer and fast-food store density and proximity) and within-store factors (in-store data on price and availability for supermarkets and greengrocers) obtained through objective audits. Multilevel regression analyses were used to examine associations of neighbourhood disadvantage with fruit, vegetable and fast-food consumption, and to test whether nutrition environment factors mediated these associations. After controlling for individual-level demographic and socioeconomic factors, neighbourhood disadvantage was associated with less vegetable consumption and more fast-food consumption, but not with fruit consumption. Some nutrition environmental factors were associated with both neighbourhood disadvantage and with diet. Nutrition environmental features did not mediate neighbourhood-disadvantage variations in vegetable or fast-food consumption. Although we found poorer diets among women living in disadvantaged neighbourhoods in Melbourne, the differences were not attributable to less supportive nutrition environments in these neighbourhoods.


The use of macromolecular protease inhibitors to study liposome-cell interactions.
A method is introduced that quantitates the release of a high molecular weight compound from small unilamellar vesicles. The technique is based on the liposomal encapsulation of trypsin inhibitor from bovine lung. Because liposomes are impermeable to all components of the test system (inhibitor, enzyme, macromolecular substrate), only the free inhibitor released from disturbed liposomes is measured. Using this technique, the exit of the macromolecular solute from liposomes induced by erythrocyte ghosts was studied. The results were compared with the leakage of a low molecular weight fluorescent marker. They indicate that, especially during the first hours of incubation, ghost-induced release of solutes is dependent on their size.


[Economic assessment of low flow anesthesia with analysis of the break-even point. Experience at an underutilized operating room].
Many authors indicate the importance of economic saving obtained with the use of the inhalation rebreathing anaesthesia instead of non rebreathing anaesthesia, always referring to parameters which are the duration of anesthesia (1 hour) and the use of the operating theatre each year. It is presumed that the utilization of rebreathing system is at least a 1.000 hours/year. However it is not necessary that all the operating theatres employ 1.000 hours/year in rebreathing anesthesia. This method requires annual depreciation costs of the capital invested for the purchase of new adequate ventilators, to modificative those already existing and guarantee adequate monitoring and the maintenance of these equipment. The importance is stressed of individuating a method of economical evaluation comparing the effective savings obtained with the real utilization of rebreathing anesthesia for each operating theatre and the costs of purchasing and maintaining the equipment. From our point of view the break-even point analysis has demonstrated to be a consistent instrument for the evaluation of the real economic advantage of rebreathing system in each hospital. It is suggested to utilize a conventional formula for the determination of the break even point, which means the minimal number of hours for year that justifies economically the adoption of rebreathing anaesthesia. An example of this analysis has been applied for an operating theatre in the hospital of Morbegno, where the major utilization of regional anaesthesia leads to a reduced number hours/year of rebreathing anesthesia which remains anyhow economically advantageous.


Physical characterization and evaluation of HPLC columns packed with superficially porous particles.
Two HPLC columns packed with superficially porous packing material (Kinetex™ 1.7 and 2.6 μm C18 particles) were evaluated in terms of their physical properties and performance characteristics. These columns were compared to a column packed with a sub-2 μm totally porous material and to a Halo(TM) column packed with 2.7 μm C18 superficially porous packing. The columns packed with superficially porous particles displayed a comparably narrower size distribution, which is narrower than the distribution of the totally porous sub-2 μm particles. Physical characteristics of the Kinetex™ particles were evaluated in terms of surface area, pore diameter, and specific pore volume. Total, external, internal, and shell porosities among the four different columns were evaluated and compared. The specific permeability for the Kinetex™ columns showed values close to those predicted by the Kozeny-Carman equation. All four columns were evaluated in terms of their chromatographic performance and compared using the Knox equation. The columns packed with the 2.6 and 2.7 μm superficially porous materials showed reduced plate heights below 2, whereas the sub-2 μm particles showed values of 2.2 and above.


Betamethasone and adult rat lung surfactant lipids.
Betamethasone (2 mg/kg/day) was administered to adult male rats (n = 15) for one week by daily subcutaneous injections. Thereafter the lungs were lavaged and lamellar bodies (intracellular surfactant storage granules) were isolated from the tissue. Lipid analyses showed two- to fourfold higher amounts of total phospholipids and disaturated phosphatidylcholine compared with the control. These changes were not found in the kidney liver and were not present in plasma membrane, mitochondrial or microsomal fractions from lungs. It was concluded that glucocorticoids plays a significant effect in increasing the lung surfactant lipid pools of adult rat lungs by changing the phospholipid content of lamellar bodies.


[Research progresses of the synthesis and application of oligopeptide containing Arg-Gly-Asp sequence].
Arg-Gly-Asp (RGD) is one of the oligopeptides with biological activity found in recent years. It is the minimum ammonia serial on the ligand, which can be recognized by most of the integrins. It has important influence on the recognition of endothelial cell, anti-thrombus and anti-tumour function, and the therapy of burn and skin helcosis. In this review, the synthesis and application of oligopeptide [correction of oligepoptide] containing RGD sequence were discussed.


Properties of an Aminotransferase of Pea (Pisum sativum L.).
A transaminase (aminotransferase, EC 2.6.1) fraction was partially purified from shoot tips of pea (Pisum sativum L. cv. Alaska) seedlings. With alpha-ketoglutarate as co-substrate, the enzyme transaminated the following aromatic amino acids: d,l-tryptophan, d,l-tyrosine, and d,l-phenylalanine, as well as the following aliphatic amino acids: d,l-alanine, d,l-methionine, and d,l-leucine. Of other alpha-keto acids tested, pyruvate and oxalacetate were more active than alpha-ketoglutarate with d,l-tryptophan. Stoichiometric yields of indolepyruvate and glutamate were obtained with d,l-tryptophan and alpha-ketoglutarate as co-substrates. The specific activity was three times higher with d-tryptophan than with l-tryptophan.


Increased peripheral blood leukocyte subsets with regulatory phenotype in clinically stable long-term HIV-infected hemophilia patients on HAART may be beneficial and contribute to a decrease in autoimmunity.
After initiation of highly-active antiretroviral therapy (HAART), long-term HIV-infected hemophilia patients have been shown to lose autoantibodies against CD4(+) peripheral blood leukocytes (PBL), suggesting that HAART induces autoimmunity-blocking mechanisms. We compared cytokine levels and subpopulations of lymphocytes and dendritic cells (DC) in the blood of 40 long-term HIV(+) patients with those of 13 long-term HIV(-) hemophilia patients; 23 HIV(+) patients had a detectable retroviral load. Cell subsets were determined using flow cytometry and cytokine levels were measured using ELISA. HIV(+) patients showed higher proportions of DC subpopulations with immunostimulatory phenotypes (p < 0.01), CD8(+) PBL (p < 0.001), and IL-2 (p < 0.001) and sIL-2R plasma levels (p = 0.002) than HIV(-) patients. They also exhibited increased proportions of T PBL with immunosuppressive phenotypes such as CD3(+)CD4(+)CD25(+)Foxp3(+) (p = 0.001), and CD3(+)CD8(+)CD28(-)Foxp3(+) PBL (p < 0.001), and a decreased IL-7R expression on CD3(+)CD8(+) PBL (p = 0.001) compared to HIV(-) patients. Frequencies of CD3(+)CD4(+)CD25(+) PBL producing IL-2, IL-4, IL-10, IL-12, and/or IFN-gamma, and of CD3(+)CD4(+)CD28(-) PBL secreting IL-2 and/or IL-4 were lower in HIV(+) than in HIV(-) patients (p <or= 0.02). Proportions of CD4(+) PBL coated with IgG, IgM, and C3d were similar in HIV(+) and HIV(-) patients (p = n.s.). However, the proportion of CD4(+)gp120(+) PBL was higher in HIV(+) patients (p = 0.002), and associated with low CD3(+)CD4(+)CD25(+)Foxp3(+) PBL (p = 0.012). We conclude that long-term HIV-infected hemophilia patients on HAART show an adaptive immune response, presumably against HIV, in the presence of upregulated immunosuppressive T PBL, downregulated cytokine-producing CD4(+) PBL, and downregulated IL-7R expression on CD8(+) PBL. Increased immunoregulatory T PBL might decrease autoimmunity, thereby contributing to immunological reconstitution and stabilization of long-term HIV-infected hemophilia patients on HAART.


Iron induction of ferritin synthesis in soybean cell suspensions.
In animal cells specialized for iron storage, iron-induced accumulation of ferritin is known to result from a shift of stored mRNA from the ribonucleoprotein fraction to polysomes. Previous reports with bean leaves suggested that in plants iron induction of ferritin synthesis would result from a regulation at the transcriptional level (F van der Mark, F Bienfait, H van der Ende [1983] Biochem Biophys Res Commun 115:463-469). Soybean (Glycine max, cv Mandarin) cell suspension cultures have been used here to support these findings. Ferritin induction is obtained by addition of Fe-citrate to the culture medium. A good correlation is found between cellular iron content and the amount of ferritin accumulation. This protein accumulation corresponds to an increase of in vitro translatable ferritin mRNA. Addition of 4 micrograms actinomycin D per milliliter to the cultures inhibits completely in vivo RNA synthesis, whereas protein synthesis was poorly affected, at least for 24 hours. During the same time, this concentration of actinomycin D strongly inhibits the iron-induced synthesis of ferritin. These results show that in soybean cell cultures, the mechanism of regulation of ferritin synthesis in response to iron does not result from recruitment of preexisting mRNA. They confirm that in plant systems, ferritin synthesis results from increased transcription of the corresponding genes.


Linear array of cesium atoms assisted by uracil molecules on Au(111).
Based on STM imaging and DFT calculations, we demonstrate that it is feasible to construct a series of metal-organic U + Cs structures composed of configuration-adjustable multiple-metal-center motifs, which is the consequence of the synergy and competition between hydrogen bonds and ionic bonds. Moreover, assisted by U molecules, the central Cs cations tend to form linear arrays.


Social comparison processes, narrative mapping and their shaping of the cancer experience: a case study of an elite athlete.
Drawing on data generated by life history interviews and fieldwork observations we illuminate the ways in which a young elite athlete named David (a pseudonym) gave meaning to his experiences of cancer that eventually led to his death. Central to this process were the ways in which David utilized both social comparisons and a narrative map provided by the published autobiography of Lance Armstrong (2000). Our analysis reveals the selective manner in which social comparison processes operated around the following key dimensions: mental attitude to treatment; the sporting body; the ageing body; and physical appearance. The manner in which different comparison targets were chosen, the ways in which these were framed by Armstrong's autobiography, and the work that the restitution narrative as an actor did in this process are also examined. Some reflections are offered regarding the experiential consequences of the social comparison processes utilized by David when these are shaped by specific forms of embodiment and selective narrative maps of cancer survival.


[Risk factors of food allergy].
Food allergy or allergic food hypersensitivity is defined as an adverse immunologic reaction caused by immunologic mechanisms mediated or not by IgE. It is a complex disease influenced by polygenetic heritance and environmental factors. Many risk factors have been investigated, pre natal and post natal, and variable and controversial results have been obtained. The most important risk factors associated with food allergy are atopy, lack of breast feeding at least three to six months and early weaning (before four-six months).


Assessing the health literacy levels of patients using selected hospital services.
The aim of this study was to assess the health literacy abilities of patients in an urban and suburban hospital. Inadequate health literacy is a widespread problem that is associated with insufficient self-care knowledge and behavior, inappropriate use of emergency services, higher rates of hospitalization, and increased healthcare costs. Knowledge of patients' reading ability is necessary to ensure that appropriately leveled printed health education materials are available. The health literacy of a convenience sample of 21 inpatients and 34 outpatients from an urban and suburban hospital was measured using the Test of Functional Health Literacy in Adults and the Rapid Estimate of Adult Literacy in Medicine. Variables for analysis included demographic characteristics, perceived health status, highest grade of school completed, socioeconomic status, healthcare costs, and number of inpatient and outpatient admissions over the previous year. Based on the Rapid Estimate of Adult Literacy in Medicine, 33% of patients had health literacy levels that were eighth grade or below, whereas according to the Test of Functional Health Literacy in Adults, 23% had marginal or inadequate functional health literacy. Literacy was significantly related to socioeconomic status (P < .001) and education (P < .001), although 30% of participants had a reading level below the highest grade completed. No other significant correlations were found. Clinical nurse specialists should ensure that health information materials are written at appropriate levels and educate nurses and other healthcare professionals to use effective communication and teaching strategies.


Time to get moving: assisted gene flow of forest trees.
Geographic variation in trees has been investigated since the mid-18th century. Similar patterns of clinal variation have been observed along latitudinal and elevational gradients in common garden experiments for many temperate and boreal species. These studies convinced forest managers that a 'local is best' seed source policy was usually safest for reforestation. In recent decades, experimental design, phenotyping methods, climatic data and statistical analyses have improved greatly and refined but not radically changed knowledge of clines. The maintenance of local adaptation despite high gene flow suggests selection for local adaptation to climate is strong. Concerns over maladaptation resulting from climate change have motivated many new genecological and population genomics studies; however, few jurisdictions have implemented assisted gene flow (AGF), the translocation of pre-adapted individuals to facilitate adaptation of planted forests to climate change. Here, we provide evidence that temperate tree species show clines along climatic gradients sufficiently similar for average patterns or climate models to guide AGF in the absence of species-specific knowledge. Composite provenancing of multiple seed sources can be used to increase diversity and buffer against future climate uncertainty. New knowledge will continue to refine and improve AGF as climates warm further.


Biweekly administration of 24-h infusion of irinotecan followed by a 1-h infusion of docetaxel: a phase I study.
We developed a chemotherapy combination regimen based on preclinical data suggesting synchronization of cancer cells in G2/M phase when exposed to irinotecan over a protracted period. This phase I study aimed to determine the toxicity spectrum, and define the dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and recommended optimal dose (ROD) of irinotecan infused over 24 h and followed by a 1-h infusion of 30 mg/m2 docetaxel. Starting dose for irinotecan was 30 mg/m2 and escalation proceeded at 30 mg/m2 increments, in cohorts of three to six patients until the MTD was reached. A dose between the MTD and the previous level was explored to further define the ROD. Thirty-two patients with advanced refractory cancers (median age 64, 19 male) received 190 treatment courses at five dosing levels of irinotecan: 30 mg/m2 (n=6 patients), 60 (n=3), 90 (n=7), 120 (n=8) and 105 (n=8). The MTD and ROD was 120/30 and 105/30 mg/m2. DLTs were diarrhea and neutropenia. Antitumor activity was modest. The ROD of biweekly administration of 24-h irinotecan followed by 1-h docetaxel is 105 and 30 mg/m2, respectively. The low hematological toxicity and modest activity observed leave questions concerning the optimal timing of this combination.


A mutant form of PTEN linked to autism.
The tumor suppressor, phosphatase, and tensin homologue deleted on chromosome 10 (PTEN), is a phosphoinositide (PI) phosphatase specific for the 3-position of the inositol ring. PTEN has been implicated in autism for a subset of patients with macrocephaly. Various studies identified patients in this subclass with one normal and one mutated PTEN gene. We characterize the binding, structural properties, activity, and subcellular localization of one of these autism-related mutants, H93R PTEN. Even though this mutation is located at the phosphatase active site, we find that it affects the functions of neighboring domains. H93R PTEN binding to phosphatidylserine-bearing model membranes is 5.6-fold enhanced in comparison to wild-type PTEN. In contrast, we find that binding to phosphatidylinositol-4,5-bisphosphate (PI(4,5)P(2)) model membranes is 2.5-fold decreased for the mutant PTEN in comparison to wild-type PTEN. The structural change previously found for wild-type PTEN upon interaction with PI(4,5)P(2), is absent for H93R PTEN. Consistent with the increased binding to phosphatidylserine, we find enhanced plasma membrane association of PTEN-GFP in U87MG cells. However, this enhanced plasma membrane association does not translate into increased PI(3,4,5)P(3) turnover, since in vivo studies show a reduced activity of the H93R PTEN-GFP mutant. Because the interaction of PI(4,5)P(2) with PTEN's N-terminal domain is diminished by this mutation, we hypothesize that the interaction of PTEN's N-terminal domain with the phosphatase domain is impacted by the H93R mutation, preventing PI(4,5)P(2) from inducing the conformational change that activates phosphatase activity.


Increase of the P1 Lys/Leu substrate preference of carboxypeptidase Y by rational design based on known primary and tertiary structures of serine carboxypeptidases.
The P1 substrate preference of serine carboxypeptidases, as expressed by the Lys/Leu ratio, differs by up to 10(5)-fold. Predictions of the major determinants of this preference are made by correlating primary and tertiary structures to substrate preferences. In carboxypeptidase Y from yeast it is predicted that Trp312 constitutes such a determinant, reducing the P1 Lys/Leu substrate preference of this enzyme. The predictions are tested by the construction and kinetic characterization of ten mutant enzymes of carboxypeptidase Y. All of these enzymes exhibit changes in their P1 substrate preference. Generally, small decreases in activity (kcat/Km) are observed with substrates containing uncharged P1 side chains. With substrates containing acidic P1 side chains, i.e., FA-Glu-Ala-OH, the activity generally increases slightly, 7-fold in the case of W312K. The most dramatic effects of the Trp312 substitutions are observed with substrates containing basic P1 side chains, i.e., kcat/Km for the hydrolysis of Fa-Lys-Ala-OH with W312E has increased 1150-fold, exclusively as a result of increased kcat values. Similar results have previously been obtained by mutational substitution at position 178 of carboxypeptidase Y. The construction and kinetic characterization of position 178 + 312 double mutants demonstrate that the kinetic effects of substitutions at these two positions are not additive. The P1 Lys/Leu substrate preference of one double mutant, L178D + W312D, has changed 380,000-fold as compared to the wild type enzyme, and the overall P1 substrate preference of this enzyme closely resembles that of carboxypeptidase WII from wheat.


Substrate recognition of nitrogenase-like dark operative protochlorophyllide oxidoreductase from Prochlorococcus marinus.
Chlorophyll and bacteriochlorophyll biosynthesis requires the two-electron reduction of protochlorophyllide a ringDbya protochlorophyllide oxidoreductase to form chlorophyllide a. A light-dependent (light-dependent Pchlide oxidoreductase (LPOR)) and an unrelated dark operative enzyme (dark operative Pchlide oxidoreductase (DPOR)) are known. DPOR plays an important role in chlorophyll biosynthesis of gymnosperms, mosses, ferns, algae, and photosynthetic bacteria in the absence of light. Although DPOR shares significant amino acid sequence homologies with nitrogenase, only the initial catalytic steps resemble nitrogenase catalysis. Substrate coordination and subsequent [Fe-S] cluster-dependent catalysis were proposed to be unrelated. Here we characterized the first cyanobacterial DPOR consisting of the homodimeric protein complex ChlL(2) and a heterotetrameric protein complex (ChlNB)(2). The ChlL(2) dimer contains one EPR active [4Fe-4S] cluster, whereas the (ChlNB)(2) complex exhibited EPR signals for two [4Fe-4S] clusters with differences in their g values and temperature-dependent relaxation behavior. These findings indicate variations in the geometry of the individual [4Fe-4S] clusters found in (ChlNB)(2). For the analysis of DPOR substrate recognition, 11 synthetic derivatives with altered substituents on the four pyrrole rings and the isocyclic ring plus eight chlorophyll biosynthetic intermediates were tested as DPOR substrates. Although DPOR tolerated minor modifications of the ring substituents on rings A-C, the catalytic target ring D was apparently found to be coordinated with high specificity. Furthermore, protochlorophyllide a, the corresponding [8-vinyl]-derivative and protochlorophyllide b were equally utilized as substrates. Distinct differences from substrate binding by LPOR were observed. Alternative biosynthetic routes for cyanobacterial chlorophyll biosynthesis with regard to the reduction of the C8-vinyl group and the interconversion of a chlorophyll a/b type C7 methyl/formyl group were deduced.


Schedule-dependent antitumor effect of gemcitabine in in vivo model system.
Gemcitabine (2',2'-difluorodeoxycytidine, dFdC, LY188011) is a new deoxycytidine analog with preclinical antitumor activity in solid tumors from murine and human origin. Of particular importance is the fact that the therapeutic effects of gemcitabine at the maximum tolerated dose level are dependent on the administration schedule. This paper describes the sensitivity pattern of gemcitabine in human head and neck squamous cell carcinoma, ovarian carcinoma, and soft tissue sarcoma, all growing as xenografts in athymic nude mice. The drug was injected intraperitoneally in various schedules at equitoxic, maximum tolerated dose levels, resulting in a reversible weight loss that varied between 5% and 15%. Generally, it was found that treatment with 120 mg/kg gemcitabine, injected four times at 3-day intervals, was more effective than the schedules of daily (five times 2.5 to 3.5 mg/kg) or weekly (two times 240 mg/kg) injections. Other workers have shown that this 3-day interval schedule also was active in human pancreas and lung carcinoma xenografts. Additional experiments were performed on normal mice bearing the colon 26-10 murine colon carcinoma. The effect of a continuous intravenous infusion system was investigated by giving two injections of 15 mg/kg gemcitabine for 24 hours at a 7-day interval. Interestingly, the efficacy of treatment increased dramatically with this infusion schedule, producing complete remissions in most tumors. In conclusion, our data on the effect of gemcitabine in animal tumor models indicate that (1) the time interval between push injections is important when intermittent schedules are used and (2) continuous infusions over a 24-hour period can be very effective in in vivo models.


Impact of concomitant use of proton pump inhibitors and clopidogrel or ticagrelor on clinical outcomes in patients with acute coronary syndrome.
There is great debate on the possible adverse interaction between proton pump inhibitors (PPIs) and clopidogrel. In addition, whether the use of PPIs affects the clinical efficacy of ticagrelor remains less known. We aimed to determine the impact of concomitant administration of PPIs and clopidogrel or ticagrelor on clinical outcomes in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). We retrospectively analyzed data from a "real world", international, multi-center registry between 2003 and 2014 (n = 15,401) and assessed the impact of concomitant administration of PPIs and clopidogrel or ticagrelor on 1-year composite primary endpoint (all-cause death, re-infarction, or severe bleeding) in patients with ACS after PCI. Of 9429 patients in the final cohort, 54.8% (n = 5165) was prescribed a PPI at discharge. Patients receiving a PPI were older, more often female, and were more likely to have comorbidities. No association was observed between PPI use and the primary endpoint for patients receiving clopidogrel (adjusted HR: 1.036; 95% CI: 0.903-1.189) or ticagrelor (adjusted HR: 2.320; 95% CI: 0.875-6.151) (P interaction = 0.2004). Similarly, use of a PPI was not associated with increased risk of all-cause death, re-infarction, or a decreased risk of severe bleeding for patients treated with either clopidogrel or ticagrelor. In patients with ACS following PCI, concomitant use of PPIs was not associated with increased risk of adverse outcomes in patients receiving either clopidogrel or ticagrelor. Our findings indicate it is reasonable to use a PPI in combination with clopidogrel or ticagrelor, especially in patients with a higher risk of gastrointestinal bleeding.


Effect of monensin on secretion of basement membrane collagen by cultured rabbit corneal endothelial cells in comparison with rabbit tendon fibroblasts.
Monensin, a monovalent ionophore, affects differently the secretion of basement membrane collagen and interstitial procollagen. At 1 X 10(-8) M, monensin inhibited only slightly the secretion of procollagen synthesized by tendon cells while secretion of basement membrane collagen synthesized by endothelial cells was inhibited by 43% after 2 hours of labelling. At higher concentration (1 X 10(-6) M), the secretion of type I procollagen by tendon cells was inhibited after two h (36%) or 24 h (24%) of labelling. The pattern of basement membrane collagen secretion varied from inhibition to stimulation depending on the labeling time. No changes in the phenotypic expression of collagen were observed in either the monensin-treated tendon cultures or endothelial cells. Phase-contrast microscopy revealed differential responses of cells to monensin: tendon cells appeared spindle-shaped or rounded-up, in contrast to the enlarged shape displayed by endothelial cells.


Influence of family communication structure and vanity trait on consumption behavior: a case study of adolescent students in Taiwan.
The purpose of this research was to study the relationship between family communication structure, vanity trait, and related consumption behavior. The study used an empirical method with adolescent students from the northern part of Taiwan as the subjects. Multiple statistical methods and the SEM model were used for testing the hypotheses. The major findings were: (1) Socio-orientation has a significant effect on how physical appearance is viewed, and concept-orientation has a significant positive effect on achievement vanity. (2) how physical appearance is viewed has a significant positive effect on all dimensions of materialism, concerns about clothing, and use of cosmetics. (3) Achievement vanity has a significant positive relationship with price-based prestige sensitivity and concerns regarding clothing. The findings have implications for marketing theory as well as for practical applications in marketing.


Reduced IL-35 in patients with immune thrombocytopenia.
: The occurrence and development of primary immune thrombocytopenia is closely related to autoimmune imbalanced. Thus, we conducted the current study to investigate the modulation of IL-35, a newly identified immunological self-tolerance factor on immune thrombocytopenic purpura (ITP). We were enrolled peripheral blood in 21 adult healthy volunteers, 21 active primary ITP patients and 16 ITP patients in remission. In the same period, bone marrow plasma was drawn from active primary ITP patients and 16 bone marrow donors. Enzyme-linked immunoassay was used to measure IL-35 levels in bone marrow mononuclear cells and peripheral blood mononuclear cells. Real-time quantitative PCR was used to study the mRNA expression levels of p35, Epstein-Barr virus-induced gene 3 in bone marrow mononuclear cells and peripheral blood mononuclear cells. Compared with the normal group, IL-35 levels of in ITP patients were decreased significantly. IL-35 level in bone marrow plasma was decreased more significantly than that in peripheral blood plasma at the same stage. The results showed that plasma IL-35 levels were significantly decreased in patients with active ITP compared with those of control individuals, and IL-35 levels in bone marrow plasma were decreased more significantly compared with those at the same stage. The pathogenesis of ITP is associated with decreased IL-35 levels. Further studies are needed to expand sample content and explore more in-depth investigate a possible role of IL-35 in the pathogenesis and course of ITP.


Significance of cytomegalovirus (CMV)-pp65 antigenemia in the diagnosis of CMV disease in human immunodeficiency virus-infected patients.
To establish the diagnostic value of the cytomegalovirus (CMV)-pp65 antigenemia in CMV disease occurring in human immunodeficiency (HIV)-infected patients, CMV-pp65 antigen in polymorphonuclear leukocytes (PMNLs) was assayed in 373 samples from 138 randomly included patients followed up for symptomatic HIV-1 infection and the correlation between CMV-pp65 antigenemia and diagnosis of CMV disease was investigated. Thirty-seven CMV disease episodes were observed in 30 patients and 89.2% of these episodes were associated with a positive CMV-pp65 antigenemia. In contrast, 94% of the patients negative for CMV-pp65 antigenemia remained free of CMV disease. Patients with CMV disease had significantly higher levels of CMV-pp65 antigenemia than CMV disease-free patients (695 positive cells/2 x 10(5) PMNLs vs. 28 positive cells/2 x 10(5) PMNLs). The positive and negative predictive values of the test were 45% and 94%, respectively, but were 93% and 80%, respectively, when a CMV-pp65 antigenemia level of > 100 positive cells/2 x 10(5) PMNLs was taken into consideration. These results indicate that the CMV-pp65 antigenemia assay is useful for the diagnosis and monitoring of CMV disease in HIV-infected patients.


A new Schiff base coordinated copper(II) compound induces apoptosis and inhibits tumor growth in gastric cancer.
Gastric cancer, as a multifactorial disorders, shows cytological and architectural heterogeneity compared to other gastrointestinal cancers, making it therapeutically challenging. Cisplatin is generally used in clinic for gastric cancer treatment but with toxic side effects and develops resistance. Anti-tumor properties of copper and its coordinated compounds have been explored intensively in recent years. In this study, we synthesized a novel Schiff base copper coordinated compound (SBCCC) and examined its antitumor effects in two gastric cancer cell lines SGC-7901 and BGC-823 as well as a mouse model of gastric cancer. The results show that SBCCC can significantly inhibit the proliferation of gastric cancer cells in a dose- and time-dependent manner. The IC50 of SBCCC in SGC-7901 and BGC-823 cells is 1 μM, which is much less than cisplatin's IC50. SBCCC induces apoptosis and causes cell cycle arrest at the G1 phase. SBCCC induces apoptosis via multiple pathways including inhibition of NF-κB, ROS production and autophagy. The synthesized SBCCC induced cancer cell death via inhibition of NF-κB, ROS production and autophagy. The multiple cell-killing mechanisms were important to overcome therapeutic failure because of multidrug-resistance of cancer cells. SBCCC, with a lower IC50 compared to cisplatin, could render it the potential to overcome the side-effect for clinical application.


Predictors of warfarin use in atrial fibrillation patients in the inpatient setting.
There is substantial published evidence that warfarin reduces the risk of stroke in patients with atrial fibrillation (AF). However, the current literature suggests that not all patients who could benefit from warfarin receive the drug. To evaluate patient-related demographic and clinical factors that could influence warfarin use or other anticoagulant use in hospitalized patients with AF. Retrospective observational study using claims data from the Wolters Kluwer Pharma Solutions Hospital Patient Level Database, evaluating characteristics of patients hospitalized in the US between 1 November 2003 and 31 October 2004. Hospital care. The study included 44,193 patients aged >or=40 years who were hospitalized between 1 November 2003 and 31 October 2004 and had a diagnosis of AF during hospitalization (AF did not need to be the cause of hospitalization). Use of warfarin or other anticoagulants (unfractionated heparin [UFH] or low-molecular-weight heparin [LMWH]) was evaluated. A logistic regression model was used to identify factors associated with warfarin use, international normalized ratio (INR) monitoring, or the use of anticoagulants (UFH or LMWH). In this analysis of hospitalized patients with AF in the real-world setting, about 56% of patients received anticoagulation therapy with warfarin. Elderly patients aged >or=75 years were less likely to be treated with warfarin than younger patients, but patients between the ages of 60 and 74 years were more likely to use warfarin than their younger counterparts. Except for patients with congestive heart failure or vascular malformation, patients with other bleeding risk factors (hepatic disease, renal disease, aspirin use, and fractures) were significantly less likely to receive warfarin than those without these risk factors. CHADS(2) scores for stroke risk of 2 and 3 were associated with a significantly higher likelihood of warfarin treatment than scores of 0 or 1. Patients admitted through a routine admission (an outpatient department) were significantly more likely to be prescribed warfarin than patients admitted through an emergency room. Patients aged >or=75 years and aspirin users were more likely to have their INR monitored during hospitalization. With respect to other anticoagulant use, females and older patients (>or=65 years) were less likely to use UFH or LMWH, and patients with renal disease or vascular malformation and those receiving aspirin were more likely to use UFH or LMWH than patients without these conditions/not receiving aspirin. Patients admitted through the emergency room were more likely to receive an anticoagulant than patients admitted through an outpatient department, an inpatient transfer, or any other source. Older age, female sex, and certain risk factors for bleeding, including hepatic disease, renal disease, aspirin use, and fractures, were associated with a lower likelihood of warfarin treatment, while a higher stroke risk (as indicated by CHADS(2) scores) was associated with a higher likelihood of warfarin treatment, in hospitalized patients with a diagnosis of AF. The likelihood of INR being monitored increased for patients aged >or=75 years and for aspirin users. Older patients and female patients were less likely to be prescribed other anticoagulants (UFH or LMWH) also.


Rotational effects in complex-forming bimolecular substitution reactions: A quantum-mechanical approach.
The quantum dynamics of the complex-forming S(N)2 reaction Cl(-)+CH(3)Br-->ClCH(3)+Br(-) is studied with emphasis on rotational effects. The pseudotriatomic system Cl-Me-Br is treated with a corresponding three-dimensional (3D) potential energy surface as a function of the two scattering coordinates and the enclosed angle where the geometry of the methyl group Me is optimized at each point. The 3D space is divided into three different parts, the interaction region, an intermediate region, and the asymptotic region. In line with simple classical-mechanical arguments and previous classical trajectory calculations, initial rotational motion of CH(3)Br seemingly decreases the reaction probability. However, the dynamical inclusion of the rotational degree of freedom and the presence of the many rovibrational product states overall lead to a large increase in reactivity compared to our previous collinear study on this reaction. If the reactant is rotationally excited, the higher vibrational product states are depleted in favor of lower-lying levels. Starting the reaction with rotationless reactants may end up in significant rotational excitation in the product molecules (translation-to-rotation energy transfer). On the other hand, initial rotational energy in rotationally highly excited reactants is to a large amount converted into translational and vibrational energy. The average amount of rotational energy in the products shows a twofold vibrational excitation-independent saturation (i.e., memorylessness), with respect to both initial rotational excitation and translational energy. Since only about one-half of all reactant states end in rotationless products, the reaction probability should be increased by a factor of 2; the actually larger reactivity points to other dynamical effects that play an important role in the reaction.


Efficient non-corrosive electron-transfer mediator mixtures for dye-sensitized solar cells.
The electrochemical and photoelectrochemical study of noncorrosive electron-transfer mediator mixtures for DSC is reported. These mixtures, characterized by the presence of kinetically fast organic or metal-organic redox couples in conjunction with a Co(II)/(III) relay, exhibited maximum photon-to-current conversion efficiencies (IPCE %) exceeding 80% when employed in the presence of a suitably designed MLCT sensitizer, rivaling with the performances of the classical I-/I3- electrolyte.


Long-term change in the sensitivity of tree-ring growth to climate forcing in Larix decidua.
Tree rings are widely used long-term proxy data which, if combined with long-term instrumental climate records, can provide excellent information on global climate variability. This research aimed to determine whether interannual climate-growth responses in Alpine treeline forests are stationary over time. We used tree-ring width chronologies of Larix decidua (European larch) from 17 sites and monthly temperatures and precipitation data for the period 1800-1999. Climate-growth relationships were assessed with correlation and response functions, and their stationarity and consistency over time were measured using moving correlation. Tree-ring chronologies showed similar interannual variations over the last two centuries, suggesting that the same climatic factors synchronously limited growth at most sites. The most sensitive variables showed significant transient responses varying within the time period, indicating a possible deviation from the uniformitarian principle applied to dendroclimatology. If these findings are confirmed in future studies on other species and in other regions, we suggest that time-dependent variables should be taken into account to avoid overestimation of treeline advance, future forest carbon storage in temperature-limited environments and inaccurate reconstruction of past climate variability.


Optimization and modeling of reduction of wastewater sludge water content and turbidity removal using magnetic iron oxide nanoparticles (MION).
Economic and rapid reduction of sludge water content in sewage wastewater is difficult and requires special advanced treatment technologies. This study focused on optimizing and modeling decreased sludge water content (Y1) and removing turbidity (Y2) with magnetic iron oxide nanoparticles (Fe3O4, MION) using a central composite design (CCD) and response surface methodology (RSM). CCD and RSM were applied to evaluate and optimize the interactive effects of mixing time (X1) and MION concentration (X2) on chemical flocculent performance. The results show that the optimum conditions were 14.1 min and 22.1 mg L(-1) for response Y1 and 16.8 min and 8.85 mg L(-1) for response Y2, respectively. The two responses were obtained experimentally under this optimal scheme and fit the model predictions well (R(2) = 97.2% for Y1 and R(2) = 96.9% for Y2). A 90.8% decrease in sludge water content and turbidity removal of 29.4% were demonstrated. These results confirm that the statistical models were reliable, and that the magnetic flocculation conditions for decreasing sludge water content and removing turbidity from sewage wastewater were appropriate. The results reveal that MION are efficient for rapid separation and are a suitable alterative to sediment sludge during the wastewater treatment process.


Non-canonical sequence elements in the promoter structure. Cluster analysis of promoters recognized by Escherichia coli RNA polymerase.
Nucleotide sequences of 441 promoters recognized by Escherichia coli RNA polymerase were subjected to a site-specific cluster analysis based on the hierarchical method of classification. Five regions permitting promoter subgrouping were identified. They are located at -54 +/- 4, -44 +/- 3, -35 +/- 3 (-35 element), -29 +/- 2 and -11 +/-4 (-10 element). Promoters were independently subgrouped on the basis of their sequence homology in each of these regions and typical sequence elements were determined. The putative functional significance of the revealed elements is discussed on the basis of available biochemical data. Those promoters that have a high degree of homology with the revealed sequence elements were selected as representatives of corresponding promoter groups and the presence of other sequence motifs in their structure was examined. Both positive and negative correlations in the presence of particular sequence motifs were observed; however, the degree of these interdependencies was not high in all cases, probably indicating that different combinations of the signal elements may create a promoter. The list of promoter sequences with the presence of different sequence elements is available on request by Email: firstname.lastname@example.com. serpukhov.su.


New Porous Heterostructures Based on Organo-Modified Graphene Oxide for CO2 Capture.
In this work, we report on a facile and rapid synthetic procedure to create highly porous heterostructures with tailored properties through the silylation of organically modified graphene oxide. Three silica precursors with various structural characteristics (comprising alkyl or phenyl groups) were employed to create high-yield silica networks as pillars between the organo-modified graphene oxide layers. The removal of organic molecules through the thermal decomposition generates porous heterostructures with very high surface areas (≥ 500 m2/g), which are very attractive for potential use in diverse applications such as catalysis, adsorption and as fillers in polymer nanocomposites. The final hybrid products were characterized by X-ray diffraction, Fourier transform infrared and X-ray photoelectron spectroscopies, thermogravimetric analysis, scanning electron microscopy and porosity measurements. As proof of principle, the porous heterostructure with the maximum surface area was chosen for investigating its CO2 adsorption properties.


Formal intermolecular [2 + 2] cycloaddition reaction of allenamide [corrected] with alkenes via gold catalysis.
An efficient method was developed to construct the densely functionalized cyclobutane[corrected] adducts through formal intermolecular cycloaddition of allenamides [corrected] with electron-rich olefins via gold catalysis, in which vinyl ethers/amides and electron-rich styrenes worked very well. In addition, a series of allenamide [corrected] dimerization products were prepared from the same allenamide [corrected] substrates.


Variation in photosynthetic pigments and plastoquinone contents in sugar beet chloroplasts with changes in leaf copper content.
The changes in the contents of chlorophyll (Chl) a, Chl b, carotenoid, and plastoquinone in sugar beet (Beta vulgaris) chloroplasts were investigated during Cu deficiency and resupply. With the onset of Cu deficiency, extrachloroplastic Cu decreased more rapidly than chloroplast Cu, which eventually accounted for all of the Cu present in the leaf. The ultrastructure of Cu-deficient chloroplasts did not differ from the control except in very young, severely deficient leaves. During Cu depletion and resupply, Chl a, Chl b, carotenoid, and plastoquinone contents changed concomitantly. Because of the concurrent changes in the contents of terpenoid-containing pigments and plastoquinone with Cu depletion and resupply, we suggest that Cu might be involved in the regulation of the early steps of terpenoid biosynthesis prior to the formation of geranyl-geranyl-pyrophosphate.


Chip-integrated nearly perfect absorber at telecom wavelengths by graphene coupled with nanobeam cavity.
We exploit the concept of critical coupling to graphene based chip-integrated applications and numerically demonstrate that a chip-integrated nearly perfect graphene absorber at wavelengths around 1.55 μm can be obtained by graphene nearly critical coupling with a nanobeam cavity. The key points are reducing the radiation loss and transmission possibly, together with controlling the coupling rate of the cavity to the input waveguide to be equal to the absorption rate of the cavity caused by graphene. Simulation results show that the absorption of monolayer graphene with a total length of only a few microns is raised up to 97%. Our study may have potential applications in chip-integrated photodetectors.


Mitochondrial biogenesis in skeletal muscle in response to endurance exercises.
Repeated bouts of endurance exercise stimulates mitochondrial biogenesis in skeletal muscle. The synthesis of mitochondrial proteins involves a coordinated expression of both nuclear and mitochondrial genes. During this process, multiples sites of regulation have been identified at the transcriptional and translational levels. After their synthesis, mitochondrial proteins originating from the nuclear genome are imported into newly synthesized preexisting membranes and directed to one of the four mitochondrial subcompartments. The detailed mechanisms of the endurance training-induced mitochondrial biogenesis are still poorly understood. In particular, much work is needed to identify the molecular signals able to stimulate and coordinate the expression of mitochondrial proteins in response to endurance training. This will be a great help in the future to understand clearly the intimate mechanisms of mitochondrial biogenesis in skeletal muscle and the factors involved in endurance exercise performance.


Effect of closure of live poultry markets in China on prevention and control of human infection with H7N9 avian influenza: a case study of four cities in Jiangsu Province.
As of August 2017, China had encountered five seasonal epidemics of H7N9 avian influenza. To prevent people from contracting H7N9 avian influenza, most cities closed live poultry markets (LPMs) to cut off the source of H7N9 virus. The objective of this study is to assess the impact of LPMs closure on reducing zoonotic transmission of avian influenza A (H7N9) virus and to make specific recommendations on the duration of closing the LPMs. Results show that the closure of LPMs can effectively control the spread of H7N9 avian influenza and reduce the incidence of human infection with H7N9. If cases of H7N9 avian influenza continue to occur, LPMs should close for at least 3-4 weeks in susceptible areas to control the spread of infection.


Selection and maintenance of spatial information by frontal eye field neurons.
Voluntary attention is often allocated according to internally maintained goals. Recent evidence indicates that the frontal eye field (FEF) participates in the deployment of spatial attention, even in the absence of saccadic eye movements. In addition, many FEF neurons maintain persistent representations of impending saccades. However, the role of persistent activity in the general maintenance of spatial information, and its relationship to spatial attention, has not been explored. We recorded the responses of single FEF neurons in monkeys trained to remember cued locations in order to detect changes in targets embedded among distracters in a task that did not involve saccades. We found that FEF neurons persistently encoded the cued location throughout the trial during the delay period, when no visual stimuli were present, and during visual discrimination. Furthermore, FEF activity reliably predicted whether monkeys would detect the target change. Population analyses revealed that FEF neurons with persistent activity were more effective at selecting the target from among distracters than neurons lacking persistent activity. These results demonstrate that FEF neurons maintain spatial information in the absence of saccade preparation and suggest that this maintenance contributes to the selection of relevant visual stimuli.


Beaming of Helical Light from Plasmonic Vortices via Adiabatically Tapered Nanotip.
We demonstrate the generation of far-field propagating optical beams with a desired orbital angular momentum by using a smooth optical-mode transformation between a plasmonic vortex and free-space Laguerre-Gaussian modes. This is obtained by means of an adiabatically tapered gold tip surrounded by a spiral slit. The proposed physical model, backed up by the numerical study, brings about an optimized structure that is fabricated by using a highly reproducible secondary electron lithography technique. Optical measurements of the structure excellently agree with the theoretically predicted far-field distributions. This architecture provides a unique platform for a localized excitation of plasmonic vortices followed by its beaming.


Removal of Organic Pollutants Benzene and Phenol Using Nanofiltration: A Molecular Dynamics Study.
Population growth has resulted in an increased demand for clean water. It is known that chemical pollutants such as phenol and benzene often make water unfit for consumption, and can be responsible for the appearance of diseases such as cancer. In this sense, studies aimed at decontaminating water are still necessary. In this study, molecular dynamics simulations were performed to evaluate the abilities of activated charcoal structures to adsorb benzene and phenol; the results of which were evaluated on the basis of root mean square deviations for all systems. The data were collected from the molecular dynamics (MD) trajectories and edited with the grace plotting tool. Visual molecular dynamics software was used to visualize the MD paths, and images were created using the UCSF chimera software. The results show that activated charcoal are viable alternatives for water decontamination by nanofiltration.


[Uric acid, a neglected molecule--the value of imaging].
Imaging plays a key role in two longterm effects of hyperuricemia: those on the urinary tract and on the skeletal system. This overview concentrates on the diagnosis of urinary stones and of musculoskeletal gout. Urinary stones are negative on radiography, i.e., they cannot be differentiated from the surrounding tissues, and even at intravenous urography only non specific filling defects are shown that may be hard to differentiate from blood clots and papillary necrosis whereas computed tomography without a contrast agent is highly sensitive in detecting all types of stones whether negative or positive at radiography. Gout of the musculoskeletal system usually manifests as an acute gouty arthritis after a long-standing asymptomatic hyperuricemia. An intercritical phase may follow before new acute attacks and--in up to 50%--chronic gout develop. During acute gouty arthritis imaging is non-specific. The distribution pattern, the relation of soft tissue changes and osteolytic paraarticular changes, calcifications and the lack of osteoporosis are a typical, nearly pathognomonic constellation of chronic tophaceous gout. In selected cases CT or MRI may add critical local information.


[Analysis of prevalence and variability of Legionella pneumophila and Legionella spp. strains on the basis of study of allelic profiles].
To analyze prevalence and variability of Legionella strains isolated in town Verkhnaya Pyshma located in Sverdlovsk region during prophylactic surveillance of potentially dangerous water objects in 2007 - 2008. Sequencing of mip gene was conducted for identification of species of Legionella. Multi-locus sequence typing was used for describing of allelic profiles of Legionella pneumophila strains. Five firstly identified on Russian territory strains of Legionella species were deposited in institute's collection. Sixty-three strains of L. pneumophila belonging to 28 sequence types were characterized. Relation between strains isolated in industrial building and from water supply system was demonstrated. Observations made on the basis of study of L. pneumophila strains isolated from cooling stacks of industrial plants confirmed potential danger of these objects as a source of dissemination of Legionella infection.


Investigation of sodium insertion-extraction in olivine NaxFePO4 (0 ≤x≤ 1) using first-principles calculations.
Olivine NaFePO4 has recently attracted the attention of the scientific community as a promising cathode material for Na-ion batteries. In this work we combine density functional theory (DFT) calculations and high resolution synchrotron X-ray diffraction (HRXRD) experiments to study the phase stability of NaxFePO4 along the whole range of sodium compositions (0 ≤x≤ 1). DFT calculations reveal the existence of two intermediate structures governing the phase stability at x = 2/3 and x = 5/6. This is in contrast to isostructural LiFePO4, which is a broadly used cathode in Li-ion batteries. Na2/3FePO4 and Na5/6FePO4 ground states both align vacancies diagonally within the ab plane, coupled to a Fe(2+)/Fe(3+) alignment. HRXRD data for NaxFePO4 (2/3 < x < 1) materials show common superstructure reflections up to x = 5/6 within the studied compositions. The computed intercalation voltage profile shows a voltage difference of 0.16 V between NaFePO4 and Na2/3FePO4 in agreement with the voltage discontinuity observed experimentally during electrochemical insertion.


Texas' war against substance abuse.
Texas ranks 53rd in funding for services to help alcohol and drug abusers. Studies show that one of every ten Texans are chemically dependent. The problems incurred by these abusers touches many--family, coworkers, treatment providers and more.


Transition metal induced derivatisations resulting in novel coordination behaviour of bis(oxamato) ligands.
Two mononuclear bis(oxamato) complexes with the formula [nBu4N]2[M(2,3-acbo)] (M=Ni (), Cu (), with acbo=anthra-9,10-chinone-2,3-bis(oxamato) have been synthesized starting from symmetric diethyl N,N'-anthra-9,10-chinone-2,3-bis(oxamate) (, 2,3-acboH2Et2). The crystal structures of and have been determined, verifying that the transition metal ions are eta4(kappa2N,kappa2O) coordinated by the [2,3-acbo]4- ligands. Using the asymmetric diethyl N,N'-anthra-9,10-chinone-1,2-bis(oxamate) (, 1,2-acboH2Et2) leads, under otherwise identical reaction conditions, to the novel bis(oxamato) complex [(n)Bu4N]2[Ni(1,2-acbo)] () whereby in the case of Cu(II) the derivate [nBu4N]2[Cu(aibo)2] () (aibo=anthra[1,2-d]-(imidazole-2-carboxylato)-6,11-dione) has been obtained. The crystal structures of and have been determined, displaying that the Ni(II) ion of is eta4(kappa2N,kappa2O) coordinated by the [1,2-acbo]4- ligand. The Cu(II) ion of is coordinated by two [aibo]2- ligands, giving rise to an approximately square-planar trans-bis(aibo-N,O) arrangement. Using the symmetric diethyl N,N'-4,5-dinitro-o-phenylene-bis(oxamate) (, niboH2Et2), possessing strongly electron withdrawing NO2-groups, leads under otherwise identical reaction conditions to the bis(oxamato) complex [nBu4N]2[Ni(nibo)] (), whereby in the case of Cu(II) the derivate [nBu4N]2[Cu(niqo)2] () (niqo=7,8-dinitro-2,3-quinoxalinedionato) has been obtained. The crystal structures of and have been determined, ensuring that the Ni(II) ion of is eta(4)(kappa2N,kappa2O) coordinated by the [nibo]4- ligand. The Cu(II) ion of is coordinated by four oxygen atoms of two [niqo]2- ligands, giving rise to an approximately square-planar coordination geometry.


Structures of an ATP-independent Lon-like protease and its complexes with covalent inhibitors.
The Lon proteases are a unique family of chambered proteases with a built-in AAA+ (ATPases associated with diverse cellular activities) module. Here, crystal structures of a unique member of the Lon family with no intrinsic ATPase activity in the proteolytically active form are reported both alone and in complexes with three covalent inhibitors: two peptidomimetics and one derived from a natural product. This work reveals the unique architectural features of an ATP-independent Lon that selectively degrades unfolded protein substrates. Importantly, these results provide mechanistic insights into the recognition of inhibitors and polypeptide substrates within the conserved proteolytic chamber, which may aid the development of specific Lon-protease inhibitors.


The incidence of different cystic fibrosis mutations in the Scottish population: effects on prenatal diagnosis and genetic counselling.
We present an analysis of the frequency of 16 different cystic fibrosis (CF) mutant alleles in the Scottish population. Each allele was detected in DNA amplified by the polymerase chain reaction (PCR) either directly on polyacrylamide gels, on agarose gels after restriction enzyme digestion, or by using allele specific oligonucleotides. Among 506 CF chromosomes, of predominantly Scottish origin, the frequencies of the different mutations were delta F508 0.71, G551D 0.05, G542X 0.04, R117H 0.01, 1717-1G----A 0.01, A455E + delta I507 + R553X + R560T + W1282X + 621 + 1G----T combined 0.03, unpublished 0.01, and unknown 0.13. No examples of D110H, R347P, S549N, S549I, or 2566ins AT mutations were found. The relevance of this type of analysis for both prenatal diagnosis and heterozygote screening is discussed.


Anesthetic efficacy of the palatal-anterior superior alveolar injection.
A single palatal-anterior superior alveolar, or P-ASA, injection has been reported to provide pulpal anesthesia of the four maxillary incisors and usually the canines. The authors conducted a prospective, randomized, double-blind study to compare the anesthetic efficacy of 2 percent lidocaine with 1:100,000 epinephrine and 3 percent mepivacaine using a computer-assisted injection system to administer the P-ASA injection. In a double-blind manner, the authors used a crossover design to administer randomly P-ASA injections of 1.4 milliliters of the lidocaine solution and 1.4 mL of the mepivacaine solution using the computer-assisted injection system at two appointments to 40 subjects. They used a pulp tester to test for anesthesia of the central incisors, lateral incisors and canines in four-minute cycles for 72 minutes. Anesthesia was considered successful when two consecutive maximum readings (80 readings) with the pulp tester were obtained. For the lidocaine solution, successful pulpal anesthesia ranged from 32 to 58 percent for the six anterior teeth. For the mepivacaine solution, successful pulpal anesthesia ranged from 22 to 38 percent. Except for the left canine, the lidocaine solution was significantly more likely to result in pulpal anesthesia than the use of the mepivacaine solution. The duration of pulpal anesthesia, for both solutions, declined steadily over 72 minutes. Using the computer-assisted injection system for the P-ASA injection, we concluded that the rather modest-to-low success rates of the lidocaine and mepivacaine solutions would not ensure predictable pulpal anesthesia of the four maxillary incisors and the canines.


Management of cervical intraepithelial neoplasia in departments of genitourinary medicine--a national survey.
A national survey of the methods used in the diagnosis and treatment of cervical intraepithelial neoplasia (CIN) in the departments of genitourinary medicine (GUM) in the United Kingdom had been conducted through a postal questionnaire. The findings indicate that at present of 157 responders to the questionnaire, 43 (27.3%) take an active part in the management of CIN. The different modes of management and follow-up are presented.


The etiological contribution of GABAergic plasticity to the pathogenesis of neuropathic pain.
Neuropathic pain developing after peripheral or central nerve injury is the result of pathological changes generated through complex mechanisms. Disruption in the homeostasis of excitatory and inhibitory neurons within the central nervous system is a crucial factor in the formation of hyperalgesia or allodynia occurring with neuropathic pain. The central GABAergic pathway has received attention for its extensive distribution and function in neural circuits, including the generation and development of neuropathic pain. GABAergic inhibitory changes that occur in the interneurons along descending modulatory and nociceptive pathways in the central nervous system are believed to generate neuronal plasticity, such as synaptic plasticity or functional plasticity of the related genes or proteins, that is the foundation of persistent neuropathic pain. The primary GABAergic plasticity observed in neuropathic pain includes GABAergic synapse homo- and heterosynaptic plasticity, decreased synthesis of GABA, down-expression of glutamic acid decarboxylase and GABA transporter, abnormal expression of NKCC1 or KCC2, and disturbed function of GABA receptors. In this review, we describe possible mechanisms associated with GABAergic plasticity, such as central sensitization and GABAergic interneuron apoptosis, and the epigenetic etiologies of GABAergic plasticity in neuropathic pain. Moreover, we summarize potential therapeutic targets of GABAergic plasticity that may allow for successful relief of hyperalgesia from nerve injury. Finally, we compare the effects of the GABAergic system in neuropathic pain to other types of chronic pain to understand the contribution of GABAergic plasticity to neuropathic pain.


The meaning of health: perspectives of Anglo and Latino older women.
This qualitative study, utilizing the dimensional analysis approach, was conducted to generate a substantive theory about the description and meaning of functional health from the perspectives of older Anglo and Latino women. Through focus group interviews with older Anglo and Latino women and data analysis, the investigators learned that the women's perceptions of functional health were vastly different. As planners and providers, we usually are trained in a health culture that is predominantly based on White, middle-class values. This ethnocentrism can act as a barrier leading us to disregard the notion that concepts such as health are not universally perceived. Findings from this study may enable us to achieve a closer approximation of the real experiences of our clients and to sensitize us to different world views.


Endothelial nitric oxide synthase (eNOS) (Glu298Asp) and urotensin II (UTS2 S89N) gene polymorphisms in preeclampsia: prediction and correlation with severity in Egyptian females.
Preeclampsia is a leading cause of maternal and fetal/neonatal morbidity and mortality. Early prediction of preeclampsia can minimize maternal and fetal complications. Gene polymorphisms are promising markers for early prediction of preeclampsia. To assess the value of endothelial nitric oxide synthase (eNOS) (Glu298Asp) and urotensin II (UTS2 S89N) gene polymorphisms for early prediction of preeclampsia. The preeclamptic group consisted of 53 pregnant who developed preeclampsia (35 mild and 18 severe), while the control group consisted of 65 age-matched pregnant females who completed uncomplicated pregnancies. eNOS and urotensin II gene polymorphisms were tested using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Concerning the eNOS gene polymorphism, there were highly significant differences between the two groups regarding the GG genotype as well as the G and T allele frequency (p < 0.001) and a statistically significant differences regarding the GT, TT genotypes (p = 0.002, 0.0276, respectively). Concerning the urotensin II gene polymorphisms, there were highly significant differences regarding the SS, SN genotypes as well as the S and N allele frequency (p < 0.001), statistically significant differences regarding the NN genotype (p = 0.063). Women having mutation in any of the two studied genes are at risk to develop mild preeclampsia, and those having mutations in both genes are at risk to develop severe preeclampsia, while the females with normal pregnancy are protected by the higher percentage of expression of the normal (wild allelles) of both genes.


[Comparison of computerized tomography and pathologic-anatomic findings of the abdomen in HIV infection].
In a retrospective study the results of abdominal computed tomography (CT) from 48 patients, who died of the complications of HIV infection, were compared with those obtained at autopsy. The CT diagnosis was confirmed at autopsy in 39 cases (81.3%). In nine patients CT results did not correlate with the postmortal findings. This was caused by lack of cooperation, cachexia and the time between the last CT study and the death of the patients. Nevertheless, CT with its standardised imaging planes is an important method for diagnosing and monitoring HIV-related diseases of the abdomen.


Early changes in nuclear proteins following axotomy.
Changes in protein synthesis are thought to be important in the response of the neuron to axotomy. Certain axonally transported proteins whose synthesis increases probably play important roles in regeneration of the axon. Although little is known about the regulation of these changes, the cell often controls its production of proteins at the nuclear level, where transactivating proteins modulate the transcription of specific genes. Thus, changes in nuclear proteins might be expected to be among the early events following axotomy, but such changes have not yet been described. We have addressed this issue by dissecting out single nuclei from [35S]methionine-labeled giant R2 neurons of Aplysia and analyzing the proteins by two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This procedure was used to avoid contamination with nonneuronal and nonnuclear proteins. Our results demonstrate large increases in two nuclear proteins (56 kDa and 41 kDa) and decreases in two others (77 kDa and 46 kDa) 5 h after axotomy. These are the earliest postaxotomy changes in [35S]methionine-labeled proteins that have been reported.


Keypoints to Successful Newborn Hearing Screening. Thirty Years of Experience and Innovations.
Congenital deafness is a major pediatric problem, affecting about 1.5-3 per 1000 newborns. The early treatment through cochlear implantation and auditory rehabilitation has been a historic milestone. Early diagnosis of congenital deafness is an essential requirement to obtain the best results, which is achieved through neonatal screening, a diagnostic practice that we began systematically at the Hospital Clínico in Valencia (Spain) 30 years ago. Neonatal hearing screening is successful in most developed countries. Its implementation has been slow due to the multiple difficulties that its universal application entails since it involves several health professionals and must be carried out, in a short time interval after birth. In addition, it must have a good performance that prevents the overload of other services and that requires experience and continuous adjustments in search of proper protocols. The aim of this review is to shed some light on some key points of neonatal hearing screening, highlighting our experience in the solutions to common problems. We will discuss about techniques, protocols and neonatal or nutritional factors that can influence the screening results. To a summary of our work, an update on the subject is provided with the intention of sharing experiences and facilitating the start-up of the new units.


Beneficiary travel under 38 U.S.C. 111 within the Unites. Final rule.
This document amends the beneficiary travel regulations of the Department of Veterans Affairs (VA) that provide a mechanism for payment of travel expenses within the United States under 38 U.S.C. 111 to help veterans and other persons obtain care and services from VA's Veterans Health Administration (VHA). The amended regulations more fully implement the statutory provisions governing such payments.


B7-DC, a new dendritic cell molecule with potent costimulatory properties for T cells.
Dendritic cells (DCs), unique antigen-presenting cells (APCs) with potent T cell stimulatory capacity, direct the activation and differentiation of T cells by providing costimulatory signals. As such, they are critical regulators of both natural and vaccine-induced immune responses. A new B7 family member, B7-DC, whose expression is highly restricted to DCs, was identified among a library of genes differentially expressed between DCs and activated macrophages. B7-DC fails to bind the B7.1/2 receptors CD28 and cytotoxic T lymphocyte-associated antigen (CTLA)-4, but does bind PD-1, a receptor for B7-H1/PD-L1. B7-DC costimulates T cell proliferation more efficiently than B7.1 and induces a distinct pattern of lymphokine secretion. In particular, B7-DC strongly costimulates interferon gamma but not interleukin (IL)-4 or IL-10 production from isolated naive T cells. These properties of B7-DC may account for some of the unique activity of DCs, such as their ability to initiate potent T helper cell type 1 responses.


Near infrared spectroscopy for the detection of desaturations in vulnerable ischemic brain tissue: a pilot study at the stroke unit bedside.
There is uncertainty whether bilateral near infrared spectroscopy (NIRS) can be used for monitoring of patients with acute stroke. The NIRS responsiveness to systemic and stroke-related changes was studied overnight by assessing the effects of brief peripheral arterial oxygenation and mean arterial pressure alterations in the affected versus nonaffected hemisphere in 9 patients with acute stroke. Significantly more NIRS drops were registered in the affected compared with the nonaffected hemisphere (477 drops versus 184, P<0.001). In the affected hemispheres, nearly all peripheral arterial oxygenation drops (n=128; 96%) were detected by NIRS; in the nonaffected hemispheres only 23% (n=30; P=0.17). Only a few mean arterial pressure drops were followed by a significant NIRS drop. This was however significantly different between both hemispheres (32% versus 13%, P=0.01). This pilot study found good responsiveness of NIRS signal to systemic and stroke-related changes at the bedside but requires confirmation in a larger sample.


Left atrial volume and function in patients with Behcet's disease assessed by real-time three-dimensional echocardiography.
Behçet's disease (BD), a multisystemic inflammatory disorder, has been associated with a number of cardiovascular dysfunctions, including endomyocardial fibrosis of the right heart, atrial fibrillation, ventricular arrhythmias and sudden cardiac death. The incidence and nature of cardiac involvement in BD are not yet clearly documented. Our aim was to evaluate left atrial (LA) volume and functions using real-time three-dimensional echocardiography (RT3DE) in Behcet's patients without any cardiac symptom. The study included 40 BD (16 females, 24 males and mean age of 33±7 years) and 30 healthy (11 females, 19 males and mean age of 35±6 years) subjects. All the patients' demographic parameters such as age, gender, and duration of BD were recorded. All the individuals underwent comprehensive 2D echocardiography examination, and RT3DE was performed to assess LA volumes and mechanical functions. LA maximum volume (Vmax) and before atrial contraction volume (Vpre A), LA active stroke volume and total stroke volumes (TSV), total emptying and active emptying fractions and expansion index were significantly higher in Behcet's disease patients when compared with the controls (P<0.0001 for all). LA passive emptying fraction was significantly lower in the patients with BD than in the controls (41±7 vs. 44±5, P=0.039). There were positive correlations between TSV and high-sensitive C-reactive protein level (r=0.413, P=0.008), TSV, and disease duration (r=0.417, P<0.007). Our study has shown that LA mechanical functions and volumes are impaired in BD. These results may be an early form of subclinical cardiac involvement in patients with BD who have no clinical evidence for cardiovascular disease.


The genome-scale metabolic model iIN800 of Saccharomyces cerevisiae and its validation: a scaffold to query lipid metabolism.
Up to now, there have been three published versions of a yeast genome-scale metabolic model: iFF708, iND750 and iLL672. All three models, however, lack a detailed description of lipid metabolism and thus are unable to be used as integrated scaffolds for gaining insights into lipid metabolism from multilevel omic measurement technologies (e.g. genome-wide mRNA levels). To overcome this limitation, we reconstructed a new version of the Saccharomyces cerevisiae genome-scale model, iIN800 that includes a more rigorous and detailed description of lipid metabolism. The reconstructed metabolic model comprises 1446 reactions and 1013 metabolites. Beyond incorporating new reactions involved in lipid metabolism, we also present new biomass equations that improve the predictive power of flux balance analysis simulations. Predictions of both growth capability and large scale in silico single gene deletions by iIN800 were consistent with experimental data. In addition, 13C-labeling experiments validated the new biomass equations and calculated intracellular fluxes. To demonstrate the applicability of iIN800, we show that the model can be used as a scaffold to reveal the regulatory importance of lipid metabolism precursors and intermediates that would have been missed in previous models from transcriptome datasets. Performing integrated analyses using iIN800 as a network scaffold is shown to be a valuable tool for elucidating the behavior of complex metabolic networks, particularly for identifying regulatory targets in lipid metabolism that can be used for industrial applications or for understanding lipid disease states.


Kidney and lung injury in rats following acute diquat exposure.
Diquat (1,1'-ethylene-2,2'-bipyridylium) is a type of widely used agricultural chemical, whose toxicity results in damage to numerous tissues, including the lung, liver, kidney and brain. The aim of the present study was to establish a rat model of acute diquat exposure and explore the relationship between diquat concentration, and kidney and lung injury, in order to provide an experimental basis for clinical treatment. A total of 140 healthy adult male Wistar rats were randomly divided into control and exposure groups. The diquat solution was administered intragastrically to the exposure group at 1/2 of the lethal dose (140 mg/kg). An equal volume of water was administered to the control group. The dynamic changes in the plasma and tissue diquat levels were quantitatively determined at 0.5, 1, 2, 4, 8, 16 and 24 h following exposure using liquid chromatography mass spectrometry. The content of hydroxyproline (HYP) in the lung tissues, as well as the levels of blood urea nitrogen (BUN), creatinine (Cr), uric acid (UA), kidney injury molecule-1 (KIM-1) and tumor growth factor (TGF)-β1, were detected using western blot analysis at every time point. Lung and kidney morphology were also assessed. Electron microscopy showed that the degree of renal damage gradually increased with time. Vacuolation gradually increased, some mitochondrial bilayer membrane structures disappeared and lysosomes increased. The lung tissue damage was mild, and the cell membrane integrity and organelles were damaged to varying degrees. The plasma and organ levels of diquat peaked at ~2 h, followed by a steady decrease, depending on the excretion rate. Over time, the serum concentrations of UA, BUN, Cr and KIM-1 were all significantly increased (P<0.05). Serum KIM-1 in rats was increased after 0.5 h, and was significantly increased after 4 h, suggesting that KIM-1 is an effective predictor of early renal injury. Early TGF-β1 expression was clearly observed in renal tissue, while no clear TGF-β1 expression was observed in the lung tissue. In conclusion, the concentration of diquat in the serum and tissue of rats with acute diquat poisoning peaked at an early stage and then rapidly decreased. The renal function damage and pathological changes persisted, the lung tissue was slightly damaged with inflammatory cell infiltration, and early pulmonary fibrosis injury was not obvious.


[Long-term arterial infusion chemotherapy combined with external irradiation therapy for unresectable pancreatic cancer--a case report].
A 66-year-old man was referred to our hospital with complaints of intractable abdominal and back pain, and diagnosed to have carcinoma of the pancreatic body. At laparotomy, he was assessed as unresectable because of cancer invasion of the superior mesenteric artery and abdominal aorta. Therefore two catheters connected to an implantable access device were placed in both the gastroduodenal and splenic arteries, in addition to gastrojejunostomy and chemical splanchnicectomy, followed by postoperative external irradiation therapy. The histological examination of the specimen obtained operatively confirmed that the lesion was moderately differentiated adenocarcinoma. Also the nuclear DNA analysis, carried out cytofluorometrically, showed diploid pattern. After discharge from our hospital, the man was treated by intra-arterial infusion chemotherapy in the outpatient department every two weeks. He lived a nearly normal life with satisfactory quality for two years until he died of GI-bleeding. In addition to the fact that the biological aggressiveness of the carcinoma cells assessed by DNA ploidy was relatively low, the combined modality therapy including pain control might benefit patients.


Delirium after primary percutaneous coronary intervention in aged individuals with acute ST-segment elevation myocardial infarction: A retrospective study.
The present prospective study aimed to investigate the incidence and risk factors of delirium after primary percutaneous coronary intervention (PCI) in older adults with acute ST-segment elevation myocardial infarction (STEMI). A total of 111 patients (age, ≥65 years) with acute STEMI following primary PCI were included in the present study. Neurocognitive testing was performed using the Mini-mental State Examination on the first day of hospitalization. Post-operative delirium was assessed using the Confusion Assessment Method for the Intensive Care Unit within the first four post-operative days. A total of 32 patients (28.8%) developed delirium after primary PCI. The independent predictors of delirium were older age [odds ratio (OR)=1.192, 95% confidence interval (CI)=1.07-1.328, P=0.001], living alone (OR=4.827, 95% CI=1.315-17.725, P=0.018), history of alcohol abuse (OR=3.875, 95% CI=1.168-12.857, P=0.026), longer duration of primary PCI (OR=1.152, 95% CI=1.077-1.232, P<0.001) and post-operative pain (current pain; OR=7.663, 95% CI=1.432-41.02, P=0.017). Compared to the patients without delirium, the participants who developed delirium had longer hospital stays and a higher rate of re-admission within 30 days after discharge. The mortality within one year after discharge (one-year mortality) was similar between patients with and without delirium. In conclusion, older patients (age, ≥65 years) with acute STEMI are at a relatively high risk of delirium following primary PCI. Higher age (≥65 years), living alone, history of alcohol dependence, longer length of primary PCI (>50 min) and post-operative pain (current pain) were determined to be risk factors for delirium after primary PCI in the present cohort.


[Promoter hypermethylation and loss of heterozygosity of the APC gene in patients with familial adenomatous polyposis].
To investigate the status of hypermethylation in the promoter 1A region of the adenomatus polyposis coli (APC) gene in 3 familial adenomatous polyposis (FAP) pedigrees and to screen large fragment deletions in the APC gene. DNA from tumor tissues and corresponding normal tissues of 5 FAP patients was modified by sodium bisulfite. Then the methylation status of the APC gene was analyzed by methylation specific-PCR (MSP) and DNA sequencing. Multiplex ligation-dependent probe amplification (MLPA) was used to screen aberrations involving large fragments from all the 15 exons and promoter region of APC gene. No methylation was present in normal tissues. Hypermethylation was found in tumor tissues of one proband and her son. Loss of heterozygosity was observed in another patient from the same FAP family. Aberrant methylation of the APC promoter region provides an important mechanism for impairing APC function and may occur early during colon neoplasia progression. Loss of heterozygosity may play a role in patients with classical polyposis.


[Cathepsin S in pathogenesis of neurological diseases].
Cathepsin S, one of the lysosomal proteinases, has many important physiological functions in the nervous system, especially in process of extracellular matrix degradation and endocellular antigen presentation. Those functions are closely associated with the pathogenesis of various neurological diseases. It would be beneficial to elucidate the role of Cathepsin S in the pathogenesis of various neurological diseases.


Primary double teeth and their effect on permanent successors.
Understanding the effects of primary double tooth (PDT) on permanent successors is important to ensure healthy permanent occlusion and aesthetics. The aim of this study is to determine the prevalence and type of PDT, their effect on permanent successors, and the accompanying dental anomalies/pathologies in a Turkish population. Study design: The records of 63 PDTs in 54 healthy Caucasian children among 10,000 patients were investigated. PDTs were classified according to Aguilo's classification. The prevalence of PDT was 0.6%. Of the 63 PDTs, 14.3% were type I, 11.1% were type II, 31.7% were type III, and 41.3% were type IV; one (1.6%) was a triple tooth. Aplasia of the permanent lateral incisor was observed most frequently in association with type I (56%) PDT. All PDTs associated with a supernumerary permanent tooth were type IV. Dental anomalies/pathologies such as odontoma, talon cusp were observed. Caries involvement was observed most frequently in type IV (58.3%) PDT. The chi-squared test was used to determine whether successor aplasia depended on PDT type, and contingency coefficients (%) were calculated to determine the degree of association between aplasia and PDT type. Clinicians should assess PDT clinically and radiographically to determine whether they are associated with aplasia of permanent lateral incisors (type I) or supernumerary permanent teeth (type IV). Type IV of PDT should be sealed with sealant or resin.


Thieno[3,2-b]pyrrolo-Fused Pentacyclic Benzotriazole-Based Acceptor for Efficient Organic Photovoltaics.
A novel nonfullerene small molecular acceptor (BZIC) based on a ladder-type thieno[3,2-b]pyrrolo-fused pentacyclic benzotriazole core (dithieno[3,2-b]pyrrolobenzotriazole, BZTP) and end-capped with 1,1-dicyanomethylene-3-indanone (INCN) has been first reported in this work. Through introducing multifused benzotriazole and INCN, BZIC could maintain a high-lying lowest unoccupied molecular orbital (LUMO) energy level of -3.88 eV. Moreover, BZIC shows a low optical bandgap of 1.45 eV with broad and efficient absorption band from 600 to 850 nm due to increased π-π interactions by the covalently locking thiophene and benzotriazole units. A power conversion efficiency of 6.30% is delivered using BZIC as nonfullerene acceptor and our recently synthesized hexafluoroquinoxaline-based polymer HFQx-T as donor. This is the first time to synthesize mutifused benzotriazole-based molecules as nonfullerene electron acceptor up to date. The preliminary results demonstrate that the mutifused benzotriazole derivatives hold great potential for efficient photovoltaics.


Sitagliptin Attenuates the Cognitive Deficits in L-Methionine-Induced Vascular Dementia in Rats.
Vascular dementia (VaD) is the second most prevalent type of dementia characterized by progressive cognitive deficits and is a major risk factor for the development of Alzheimer's disease and other neurodegenerative disorders. This study is aimed at determining the potential neuroprotective effect of sitagliptin (STG) on cognitive deficits in L-methionine-induced VaD in rats and the possible underlying mechanisms. 30 adult male Wistar albino rats were divided equally (n = 10) into three groups: control, VaD, and VaD + STG groups. The cognitive performance of the animals was conducted by open field, elevated plus maze, Y-maze, novel object recognition, and Morris water maze tests. Serum homocysteine, TNF-α, IL-6, IL-10, total cholesterol, and triglycerides levels were assessed together with hippocampal MDA, SOD, and BDNF. Histopathological and immunohistochemical assessments of the thoracic aorta and hippocampus (CA1 region) were also performed. Chronic L-methionine administration impaired memory and learning and induced anxiety. On the other hand, STG protected against cognitive deficits through improving oxidative stress biomarkers, inflammatory mediators, lipid profiles, and hippocampus level of BDNF as well as decreasing caspase-3 and GFAP and increasing Ki-67 immunoreactions in the hippocampus. Also, STG improved the endothelial dysfunction via upregulation of aortic eNOS immunoreaction. STG improved the cognitive deficits of L-methionine-induced VaD by its antioxidant, anti-inflammatory, antiapoptotic, and neurotrophic effects. These findings suggest that STG may be a promising future agent for protection against VaD.


Adaptive and maladaptive mechanisms of cellular priming.
The mechanisms of cellular priming resulting in both adaptive and maladaptive responses to subsequent injury and strategies for manipulating this priming to constructive therapeutic advantage are explored. A cell is prepared or educated by an initial insult (priming stimulus). Investigations in both laboratory animals and humans indicate that cells, organs, and perhaps even whole patients respond differently to a proximal second insult ("second hit") by virtue of this prior environmental history. The opportunity to achieve the primed state appears to be conserved across almost all cell types. The initial stimulus transmits a message to the cellular machinery that influences the cell's response to a subsequent challenge. This response may result in an exaggerated inflammatory response in the case of the neutrophil (an often maladaptive process) or an improved tolerance to injury by the myocyte (adaptive response). Our global hypothesis is that cellular priming is a conserved, receptor-dependent process that invokes common intracellular targets across multiple cell types. We further postulate that these targets create a language based on the transient phosphorylation and dephosphorylation of intracellular enzymes that is therapeutically accessible. Priming is a conserved, receptor-dependent process transduced by means of intracellular targets across multiple cell types. The potential therapeutic strategies outlined involve the receptor-mediated manipulation of cellular events. These events are transmitted through an intracellular language that instructs the cell regarding its behavior in response to subsequent stimulation. Understanding these intracellular events represents a realistic goal of priming and preconditioning biology and will likely lead to clinical control of the primed state.


Cerebral blood flow measurements using stable xenon CT with very short inhalation times.
A noninvasive, simplified method using inhalation of stable xenon (Xe(s)) and computed tomographic (CT) scanning to estimate regional cerebral blood flow (rCBF) and regional partition coefficient (r lambda) is described. Twenty-four patients with cerebrovascular occlusive disease and six volunteer controls inhaled 30% Xe(s) and 70% oxygen for 180 seconds and exhaled for 144 seconds during serial CT scanning without denitrogenation. The end-tidal Xe(s) concentration was continuously monitored with a thermoconductivity analyzer to determine the build-up range (A value) and build-up rate constant (K value) for arteries with the curve fitting method. The time-CT number (Hounsfield unit) curve for cerebral tissue during the Xe(s) washin and washout phases was used to calculate r lambda and rCBF using least squares curve fitting analysis. The resultant r lambda and rCBF map demonstrated a reliable distribution between the gray and white matter, and infarcted areas. rCBF was high in gray matter, low in white matter, and much lower in infarcted areas than in white matter, r lambda was high in white matter, low in gray matter, and much lower in infarcted areas. Xe(s) CT-CBF studies with very short inhalation of 180 seconds is a clinically useful method for evaluation of rCBF in patients with cerebrovascular diseases.


DT-diaphorase activity and mitomycin C sensitivity in non-transformed cell strains derived from members of a cancer-prone family.
Non-transformed skin fibroblasts derived from five members of a cancer-prone family and three unrelated healthy volunteers were assayed for their levels of activity of the quinone reductase DT-diaphorase and for their sensitivity to the antitumor quinone mitomycin C (MMC). Previous studies of skin fibroblasts derived from one afflicted member of this family (3437T) demonstrated increased resistance to MMC under aerobic exposure conditions and a reduced level of DT-diaphorase. In the present study 3437T cells and a cell strain derived from another afflicted member of the cancer-prone family were found to be hyperresistant to the cytotoxic effects of MMC, and demonstrated negligible DT-diaphorase activity (30 +/- 10 nmol/min/mg protein). Cell strains derived from the three other family members demonstrated intermediate DT-diaphorase activity (400-800 nmol/min/mg protein). Enzyme activities of 1800-6000 nmol/min/mg protein were measured in the three control cell strains. A protein that was reactive with a rabbit polyclonal antibody raised against rat DT-diaphorase and corresponded to the known mol. wt of DT-diaphorase was clearly evident in the three control cell strains, but absent in the two MMC-hyperresistant cell strains. This protein was present in intermediate amounts in the remaining members of the cancer-prone family. Southern analysis of DNA isolated from all eight cell strains and restricted with EcoRI demonstrated the presence of a DNA sequence of approximately 15 kb which hybridized to a rat DT-diaphorase cDNA probe. Northern analysis revealed the presence of an RNA species approximately 1200 bp in size, consistent with that for a human DT-diaphorase mRNA, in all cell strains derived from family members. A post-transcriptional defect would, therefore, appear to be responsible for the decreased enzyme activity observed in the resistant cell strains. These results suggest a role for DT-diaphorase in MMC bioactivation and that reduced levels of the protein may be causally related to the cancer-prone tendency of this family.