Microengineered vascular systems for drug development.
Recent advances in microfabrication technologies and advanced biomaterials have allowed for the development of in vitro platforms that recapitulate more physiologically relevant cellular components and function. Microengineered vascular systems are of particular importance for the efficient assessment of drug candidates to physiological barriers lining microvessels. This review highlights advances in the development of microengineered vascular structures with an emphasis on the potential impact on drug delivery studies. Specifically, this article examines the development of models for the study of drug delivery to the central nervous system and cardiovascular system. We also discuss current challenges and future prospects of the development of microengineered vascular systems.


Piloting, testing and scaling parental training: a multi-partnership approach in Côte d'Ivoire.
Early Childhood Development is high on the policy agenda in Côte d'Ivoire, where the government has identified it as part of its overall approach to improve human capital outcomes. This paper describes a multi-partner approach to piloting, monitoring, adaption, testing and scaling of parental training for ECD. It discusses the learnings from the pilots, and present early evaluation results from two RCTs, focusing on parental participation in trainings and acceptability of messages, with the objective to inform national scaling strategies. As such, this paper illustrates how "MEL systems contributed to ensuring that positive early childhood development (ECD) outcomes were improved as interventions were seeking to achieve scale," one of the research questions outlined in the call description for the special issue. The paper further provides a real-world example of "How MEL systems can support contributions and buy-in from a variety of stakeholders as ECD interventions (seek to) achieve impacts at scale (e.g., through the public system)? Five training approaches to improve caregivers' knowledge and practices around nutrition, preventive health, stimulation, and disciplining were piloted at small scale between 2018 and 2020. An intensive process evaluation was embedded to identify strengths and weaknesses, adapt through an iterative phase, and ultimately make recommendations for their scale up against 11 defined criteria. In early 2021, the two most promising approaches were scaled through two clustered randomized control trials to more than 150 villages each. A cost-effectiveness study was designed in consultation with government stakeholders, centered around targeting different caregivers and decision makers in the household and the extended family and on enhancing community interactions around ECD. The evaluation of the five pilots identified one model recommended to be scaled, and one other model to scale after further adaptations. Monitoring and evaluation data from the two models at scale show high levels of participation and acceptability of core messages. Experimental variations involving community champions and fathers increase participation. The iterative and multi-partner process led to two models of parenting training that have wide acceptability. Future work will analyze impacts on cognitive and socio-emotional outcomes, together with cost analysis.


Expression of steroid receptor coactivator-1 is elevated during neuronal differentiation of murine neural stem cells.
The cell-lineage-specific fate of neural stem cells (NSCs) is defined by spatial and temporal gene expression regulated by various transcription factors and their coregulators, including coactivators and corepressors. To clarify the cellular distribution of the steroid receptor coactivator-1 (SRC-1), a ligand-dependent nuclear receptor coactivator, during neurogenesis, we examined the expression profiles of SRC-1 during the proliferation and differentiation in culture of NSCs derived from the ganglionic eminence of mouse embryos. We found that SRC-1 was rarely expressed in proliferating cells and multipotent precursors with the typical characters of NSCs. Under conditions that promote the differentiation of NSCs, both the SRC-1 transcript and protein levels were elevated and the population of SRC-1-positive cells was found to be higher in the mature neurons than in the immature neurons. In contrast, SRC-1 expression was rarely localized in the glial lineage cells, including astrocytes and oligodendrocytes. These results indicate that SRC-1 expression accompanies the appearance of neuronal-fate-committed cells derived from multipotent NSCs and is preferentially expressed in neuronal lineage cells during the differentiation of NSCs.


[Analysis of correlation between fecal and alveolar lavage fluid flora of ventilator-associated pneumonia patients based on 16S rRNA sequencing technology].
To investigate the changes and correlation of intestinal and pulmonary microecological structures in patients with ventilator-associated pneumonia (VAP). A prospective observational study was conducted. Thirty-one patients with VAP admitted to the department of critical care medicine of General Hospital of Ningxia Medical University from May 1st 2019 to May 1st 2020 were enrolled. Feces and alveolar lavage fluid samples from patients with the same day, feces and alveolar lavage specimen flora composition and the structure of biological information analysis by 16S rRNA sequencing technologies, the comprehensive sequencing results, and clinical data of patients were analyzed. (1) The diversity (abundance and diversity) of flora in the alveolar lavage fluid of VAP patients was higher than that of fecal flora. Among them, Ace index, Chao index and Shannon index describing the abundance of flora showed statistically significant differences [Ace index: 305.89 (214.39, 458.66) vs. 204.51 (165.15, 247.61), Chao index: 259.83 (194.20, 459.31) vs. 187.67 (153.28, 234.01), Shannon index: 3.01 (2.39, 3.54) vs. 2.55 (1.86, 2.95), all P < 0.05], but there was no significant difference in Simpson index describing diversity [0.14 (0.08, 0.27) vs. 0.19 (0.10, 0.33), P > 0.05]. (2) In the sequencing results of feces and alveolar lavage fluid of VAP patients, there were some intestinal related bacteria groups with high abundance, such as Escherichia-Shigella, Faecalibacterium, Bacteroides, and Lachnospira, etc. (3) In 31 VAP patients, suspicious pathogenic bacteria was found in 20 cases (6 cases of Streptococcus viridans, 5 cases of Escherichia coli, 3 cases of Klebsiella pneumoniae, 3 cases of Acinetobacter baumannii, 2 cases of Staphylococcus aureus, 1 case of Pseudomonas aeruginosa), and the same suspected pathogens also existed in the 17 patients' alveolar lavage and waste sequencing. (4) Fourteen VAP patients combined with sepsis, 14 patients without sepsis were selected for sample size matching. The results showed that, Jaccard similarity index to describe lung-correlation of intestinal flora in VAP with sepsis group was significantly elevated, and the difference was statistically significant (0.24±0.08 vs. 0.19±0.06, P < 0.01). There is a certain correlation between pulmonary and intestinal flora in VAP patients. In addition to the exclusion of pulmonary infection caused by environmental and upper respiratory micro-inhalation, the lower digestive tract may also be source of infection.


New Zealand women's experience during their first year of Jadelle® contraceptive implant.
INTRODUCTION Subsidisation of the levonorgestrel-releasing Jadelle® contraceptive implant in 2010 resulted in a rapid uptake. Clinicians had little prior experience of client satisfaction, side effect profile, and removal rate of this contraceptive method. AIM To obtain information on satisfaction, bleeding patterns, continuation rates and reasons for removal for New Zealand women during their first year of use of a subsidised contraceptive implant, Jadelle®. METHODS Women having a Jadelle® implant inserted in New Zealand Family Planning clinics were recruited to be followed up by phone, text or email at 1, 3, 6, 9 and 12 months. They were asked about their bleeding pattern, satisfaction and their views on benefits of, or problems with, implant use. RESULTS 252 women were recruited. The three common bleeding patterns in the cohort were regular periods, amenorrhoea and irregular bleeding. Eighteen percent had their implant removed within the first year with more than half of those being unhappy with their bleeding pattern. This was usually prolonged bleeding. Otherwise satisfaction rates were high throughout the year. DISCUSSION The majority of New Zealand women using Jadelle® were satisfied with this method of contraception during their first year of use. Implant removals were most likely to be related to prolonged bleeding. However the commonest bleeding pattern was regular periods. KEYWORDS Contraceptive implant; progestin; bleeding; satisfaction; continuation rate; reducing reproductive health inequalities.


Nuclear localization of IkappaB alpha is mediated by the second ankyrin repeat: the IkappaB alpha ankyrin repeats define a novel class of cis-acting nuclear import sequences.
The ability of the IkappaB alpha protein to sequester dimeric NF-kappaB/Rel proteins in the cytoplasm provides an effective mechanism for regulating the potent transcriptional activation properties of NF-kappaB/Rel family members. IkappaB alpha can also act in the nucleus as a postinduction repressor of NF-kappaB/Rel proteins. The mechanism by which IkappaB alpha enters the nucleus is not known, as IkappaB alpha lacks a discernible classical nuclear localization sequence (NLS). We now report that nuclear localization of IkappaB alpha is mediated by a novel nuclear import sequence within the second ankyrin repeat. Deletion of the second ankyrin repeat or alanine substitution of hydrophobic residues within the second ankyrin repeat disrupts nuclear localization of IkappaB alpha. Furthermore, a region encompassing the second ankyrin repeat of IkappaB alpha is able to function as a discrete nuclear import sequence. The presence of a discrete nuclear import sequence in IkappaB alpha suggests that cytoplasmic sequestration of the NF-kappaB/Rel-IkappaB alpha complex is a consequence of the mutual masking of the NLS within NF-kappaB/Rel proteins and the import sequence within IkappaB alpha. Nuclear import may be a conserved property of ankyrin repeat domains (ARDs), as the ARDs from two other ARD-containing proteins, 53BP2 and GABPbeta, are also able to function as nuclear import sequences. We propose that the IkappaB alpha ankyrin repeats define a novel class of cis-acting nuclear import sequences.


[Analysis of the eligibility of elderly colorectal cancer patients for adjuvant chemotherapy combined with polysaccharide K].
We enrolled 62 elderly patients( ≥70 years of age) with colorectal cancer who had undergone surgery and postoperative adjuvant chemotherapy at our department and analyzed the overall surviva(l OS) and disease-free surviva(l DFS) to identify the patients who responded to treatment. Postoperative adjuvant chemotherapy was performed with oral anticancer agents, including doxifluridine( 5'-DFUR), uracil/tegafur( UFT), and UFT/Leucovorin( LV); all patients also received polysaccharide K( PSK), an immunomodulator, in combination with chemotherapy. The 3-year OS and DFS rates for all patients were 83.4% and 78.6%, respectively, with no significant differences in these rates based on the chemotherapeutic agents used. The patients were assigned to low and high groups on the basis of the median cut-off values of each clinical laboratory parameter and the data obtained were subjected to univariate analysis. The results of the univariate analysis suggested that carcinoembryonic antigen (CEA) and cancer antigen 125 (CA125) levels were significant prognostic factors. Further multivariate analysis using Cox regression analysis identified the preoperative CEA level alone as an independent factor. When stratification analysis was performed using a preoperative CEA level of 4.0 ng/mL as the cut-off value, the results indicated that the outcome of patients with a high preoperative CEA level may be 8-fold worse than that of patients with a low preoperative CEA level. For these patients, the use of chemotherapeutic drugs that elicit a more potent antitumor effect should be considered.


Distinct functional domains of STP-C488 of herpesvirus saimiri.
The STP-C488 oncogene of herpesvirus saimiri has transforming activity independent of the rest of the viral genome. Three distinct structural regions can be predicted from the STP-C488 sequence: an acidic amino terminal domain, a collagen domain, and a hydrophobic carboxyl-terminal domain. To study the importance and functional roles of these regions, 25 different mutant forms of STP-C488 were generated. Net negative charge in the 17 amino acid amino-terminal domain was found to be important for protein structure and transformation. Increasing the net negative charge decreased electrophoretic mobility and decreasing net negative charge increased electrophoretic mobility. The three glutamic acid residues and overall acidity in this region were found to be necessary to retain potent transforming activity. Interruption of the 18 collagen-like repeats in the central region also interrupted transforming activity. The hydrophobic region at the carboxyl terminus was found to be important for membrane localization. The acidic amino-terminal domain is likely to be the catalytic or ligand binding site of STP-C488.


Secondary amenorrhea with normal ovulatory cycles in a young virgin with normal follicle stimulating hormone levels--a case report.
To determine if normal ovulation is possible despite amenorrhea in the absence of any obvious uterine abnormalities or adhesions. The study was conducted on a 17-year-old virgin with normal sexual development and normal secondary sexual characteristics whose menarche was at age 12 but whose menses ceased after two menstruations. She was first treated with medroxyprogesterone acetate 10 mg x ten days and then a cycle of oral contraceptives. She failed to get menses following progesterone (P) withdrawal and following a cycle of oral contraceptives. All of her pituitary function studies were normal. Her serum follicle stimulating hormone (FSH) was 3 mIU/ml, luteinizing hormone (LH) 9 mIU/ml, estradiol (E2) was 107 pg/ml and the serum P was 3.9 ng/ml. These values were consistent with recent ovulation. However menses failed to ensue. This case confirms that in humans, similar to some non-primates, ovulation is possible without shedding the endometrium. Possibly she lacked spiral arterioles similar to ovulating mammals. Her virginal introitus and lack of any serious febrile illness made Asherman's syndrome highly unlikely. Her normal menstrual cycle at age 12 not only excluded a mullerian abnormality or imperforate hymen but led to speculation as to whether anovulatory bleeding from unopposed estrogen was possible but that somehow the presence of P inhibited the endometrial shedding process. In contrast to a previously reported study, this young woman almost had primary amenorrhea whereas the former case had more menses during her life but they ceased shortly after age 30.


Characterization of Changes in Gluten Proteins in Low-Gliadin Transgenic Wheat Lines in Response to Application of Different Nitrogen Regimes.
Gluten proteins are major determinants of the bread making quality of wheat but also of important gluten-related disorders. The gluten protein accumulation during grain filling is strongly influenced by nitrogen fertilization. We have characterized the gluten proteins in low-gliadin wheat lines as influenced by nitrogen treatments in two experiments. These transgenic lines, D783, D793, C655, D577, and E82 were obtained by using two different RNAi silencing fragments and two endosperm-specific promoters to drive the silencing fragments (d-hordein and γ-gliadin). In Experiment 1, we used three nitrogen fertilizer rates (120, 360, and 1080 mg N) added at sowing stage and combined with two sulfur rates (8 and 30 mg S); Experiment 2 included two nitrogen levels (120 and 1080 mg N), which were added according to the greatest demand per plant using split applications. The protein quantification was accomplished by Reverse-Phase High-Performance Liquid Chromatography and gluten content (ppm) determined using monoclonal antibody R5 (Competitive R5 ELISA). The results showed differences in protein accumulation between the two transgenic lines with the same silencing fragment but different promoter. Lines D793 and E82 showed low gliadin and an increment in glutenin content with increasing nitrogen. Competitive ELISA R5 showed a significant decrease in gluten content using split applications of nitrogen (Experiment 2) with 120 mg N compared to Experiment 1. In addition, line E82 ensures that variations in N fertilization will not result in increased gluten content.


Kinetics of radiation-induced strand break formation in single-stranded pyrimidine polynucleotides in the presence and absence of oxygen; a time-resolved light-scattering study.
Time-resolved reductions in the light-scattering intensity (LSI) of aqueous oxic and anoxic solutions of poly-C and poly-U at pH 7.8, following pulse-irradiation, have been studied as indices of strand break formation. With doses of 3-24 Gy per pulse, a number of kinetically distinct strand breakage components have been detected. A comparison of the LSI responses obtained from irradiations conducted under N2O with those conducted under air or O2 show no marked difference in the overall extent of LSI change. However, the immediate and fast (t 1/2 less than or equal to 50 microseconds) reduction in LSI, accounting for about 18-19% of the pyrimidine polynucleotide's total LSI response in oxic solution, is reduced in the absence of oxygen, to about 12% of the total LSI response found with poly-C and to about 9% for poly-U. For poly-C there is a five-fold enhancement in the rate of major strand breakage under anoxia [k1(N2O) = 7.9s-1] whereas for poly-U a more modest enhancement (about two-fold) is observed. These enhanced rates are mirrored by those for the losses of the principal optical anoxic absorptions (observed pulse radiolytically) that are assigned to the pyrimidine 6-yl base radicals. Such findings support a proposal that the rate-limiting step of major strand breakage for pyrimidine polynucleotides is a base radical mediated hydrogen atom abstraction reaction (Lemaire et al. 1987, Hildenbrand and Schulte-Frohlinde 1989). Irradiation of poly-C and poly-U in N2O/O2 (4:1, v/v) saturated solutions yields LSI changes much larger than those noted under N2O and air (or O2), which are in turn approximately double the responses observed under N2. This indicates that the major strand breaking species of water radiolysis is the OH-radical and that there is an oxygen enhancement of single strand breakage of about 1.9 for poly-C and 1.6 for poly-U.


[Psychodynamics of psychogenic fever].
In this study we aimed to formulate a psychological framework on the origins of vegetative fever. Our sample comprised 13 patients. Concerning the structure of personality we found, that all the patients came from broken homes, that they showed pronounced disturbances in their inter-personal relationships, that they had developed an extremely exigeant ideal ego and that they strongly suppressed their aggressiveness. We were able to define two characteristic situations which can trigger vegetative fever; the break-down of the ideal ego due to external traumatic circumstances and the threat of the disolution of a symbiotic relationship. Beside the vegetative fever all our patients showed a great number of other psychological or functional disturbances. Only a few of the psychologically severely affected patients could be treated with psychotherapy. The pronounced tendency to somatize with a strong libidinal cathexis of the whole organism can be interpreted as an attempt to restore the feeling of coherence of the ego in order to avoid it's psychotic break-down (Meng).


A prototype hybrid 7π quinone-fused 1,3,2-dithiazolyl radical.
Reaction of 1,4-naphthoquinone and SNSMF(6) (M = As, Sb) in SO(2) solution in a 1 : 2 molar ratio led to the naphthoquinone fused 1,3,2-dithiazolylium salts, 3MF(6) quantitatively by multinuclear NMR (87% isolated yield of 3SbF(6)) via the cycloaddition and oxidative dehydrogenation chemistry of SNS(+) with formation of NH(4)SbF(6) and S(8). The product 3SbF(6) was fully characterized by IR, Raman, multinuclear {(1)H, (13)C, (14)N} NMR, elemental analysis, cyclic voltammetry and single crystal X-ray crystallography. The reduction of 3SbF(6) with ferrocene (Cp(2)Fe) in refluxing acetonitrile (CH(3)CN) led to the first isolation of a fused quinone-thiazyl radical, 3˙ in 73% yield. The prototype hybrid quinone-thiazyl radical 3˙ was fully characterized by IR, Raman microscopy, EI-MS, elemental analysis, solution and solid state EPR, magnetic susceptibility (2-370 K) and was found to form π*-π* dimers in the solid state as determined by single crystal X-ray crystallography. Furthermore, the thermal decomposition of 3˙ led to a novel quinone-fused 1,2,3,4-tetrathiine, 10 (x = 2) and the known 1,2,5-thiadiazole, 11. The energetics of the cycloadditon and oxidative dehydrogenation chemistry of SNS(+) and 1,4-naphthoquinone leading to 3SbF(6) were estimated in the gas phase and SO(2) solution by DFT calculations (PBE0/6-311G(d)) and lattice enthalpies obtained by the volume based thermodynamic (VBT) approach in the solid state. The gas phase ion energetics (ionization potential (IP) and electron affinity (EA)) of 3˙ are compared to related 1,3,2- and 1,2,3-dithiazolyl radicals.


Size- and food-dependent growth drives patterns of competitive dominance along productivity gradients.
Patterns of coexistence among competing species exhibiting size- and food-dependent growth remain largely unexplored. Here we studied mechanisms behind coexistence and shifts in competitive dominance in a size-structured fish guild, representing sprat and herring stocks in the Baltic Sea, using a physiologically structured model of competing populations. The influence of degree of resource overlap and the possibility of undergoing ontogenetic diet shifts were studied as functions of zooplankton and zoobenthos productivity. By imposing different size-dependent mortalities, we could study the outcome of competition under contrasting environmental regimes representing poor and favorable growth conditions. We found that the identity of the dominant species shifted between low and high productivity. Adding a herring-exclusive benthos resource only provided a competitive advantage over sprat when size-dependent mortality was high enough to allow for rapid growth in the zooplankton niche. Hence, the importance of a bottom-up effect of varying productivity was dependent on a strong top-down effect. Although herring could depress shared resources to lower levels than could sprat and also could access an exclusive resource, the smaller size at maturation of sprat allowed it to coexist with herring and, in some cases, exclude it. Our model system, characterized by interactions among size cohorts, allowed for consumer coexistence even at full resource overlap at intermediate productivities when size-dependent mortality was low. Observed shifts in community patterns were crucially dependent on the explicit consideration of size- and food-dependent growth. Accordingly, we argue that accounting for food-dependent growth and size-dependent interactions is necessary to better predict changes in community structure and dynamics following changes in major ecosystem drivers such as resource productivity and mortality, which are fundamental for our ability to manage exploitation of living resources in, e.g., fisheries.


Risk Factors in Hospitalized Patients With Burn Injuries for Developing Heterotopic Ossification--A Retrospective Analysis.
The aims of this study were to identify the risk factors for developing heterotopic ossification in patients with burns injuries and, second, to review the outcomes associated with the treatment disodium etidronate. Patients with heterotopic ossification were identified using the burns unit computer database. The control group was the patients who were the next admission after admission of the patient who subsequently developed heterotopic ossification. Demographic and clinical data were collected. Univariate and multivariate techniques were used to identify risk factors for heterotopic ossification. We reviewed 337 patients admitted over a 5-year period and identified 19 patients with heterotopic ossification (5.6%). A further 19 burn injury patients were included as controls. Heterotopic ossification developed clinically and radiologically after a median time of 37 days (interquartile range [IQR], 30-40) and 49 days (IQR, 38-118), respectively. In univariate analysis, heterotopic ossification was associated with a greater %TBSA, inhalation injury, use of mechanical ventilation, number of surgical procedures, sepsis, and longer time to active movement. In a multivariate analysis that adjusted for severity of burn injury by means of the Belgian Outcome in Burn Injury score, time to active movement was recognized as an independent risk factor for heterotopic ossification (odds ratio 1.48, 95% confidence interval 1.09-2.01). Elevations in serum calcium concentrations were the only observed adverse effects for disodium etidonrate. This study has demonstrated that %TBSA, inhalation injury, and the need for ventilatory support and the use of multiple surgical procedures are predictive of the development of heterotopic ossification.


Stressful life events and orthostatic blood pressure recovery in older adults.
The majority of the literature on stress and blood pressure (BP) concerns the increased risk of cardiovascular morbidity and mortality from high BP. Because the sympathetic nervous system is critical to the maintenance of orthostatic BP, it was hypothesized that older adults who have experienced more stressful life events (SLEs) would be more likely to show impaired recovery of BP in response to orthostatic stress. A total of 3,765 participants (Mage = 61.6 years, SD = 8.2; 54% female) from the first wave of The Irish Longitudinal Study on Ageing (TILDA) were included in the current analysis. Exposure to lifetime SLEs was ascertained by self-completion questionnaire, and beat-to-beat orthostatic BP measurement was carried out. Individuals who failed to recover at least 95% of their baseline BP by 60 s post stand were characterized as having impaired orthostatic BP recovery. An independent, dose-response relationship between the number of SLEs reported and the odds of impaired systolic BP recovery was observed after adjustment for covariates (1 event: odds ratio [OR] = 1.19, 95% confidence interval [CI] [0.98, 1.45], p = .078; 2 events: OR = 1.33, 95% CI [1.03, 1.73], p = .031; 3 or more events: OR = 1.56, 95% CI [1.12, 1.73], p = .009). This relationship was not evident for diastolic BP recovery. The reporting of a higher number of SLEs is associated with greater risk of impaired systolic BP recovery from orthostatic stress. Potential clinical implications include an increased risk of cerebral hypoperfusion, which predisposes older adults to falls, faints, and changes in cognitive status.


Ab initio studies of alkyl radical reactions: Combination and disproportionation reactions of CH3 with C2H5, and the decomposition of chemically activated C3H8.
This paper reports the first quantitative ab initio prediction of the disproportionation/combination ratio of alkyl+alkyl reactions using CH3+C2H5 as an example. The reaction has been investigated by the modified Gaussian-2 method with variational transition state or Rice-Ramsperger-Kassel-Marcus calculations for several channels producing (1) CH4+CH2CH2, (2) C3H8, (3) CH4CH3CH, (4) H2+CH3CHCH2, (5) H2+CH3CCH3, and (6) C2H6+CH2 by H-abstraction and association/decomposition mechanisms through singlet and triplet potential energy paths. Significantly, the disproportionation reaction (1) producing CH4+C2H4 was found to occur primarily by the lowest energy path via a loose hydrogen-bonding singlet molecular complex, H3CHC2H4, with a 3.5 kcal/mol binding energy and a small decomposition barrier (1.9 kcal/mol), instead of a direct H-abstraction process. Bimolecular reaction rate constants for the formation of the above products have been calculated in the temperature range 300-3000 K. At 1 atm, formation of C3H8 is dominant below 1200 K. Over 1200 K, the disproportionation reaction becomes competitive. The sum of products (3)-(6) accounts for less than 0.3% below 1500 K and it reaches around 1%-4% above 2000 K. The predicted rate constant for the disproportionation reaction with multiple reflections above the complex well, k1=5.04 x T(0.41) exp(429/T) at 200-600 K and k1=1.96 x 10(-20) T(2.45) exp(1470/T) cm3 molecule(-1) s(-1) at 600-3000 K, agrees closely with experimental values. Similarly, the predicted high-pressure rate constants for the combination reaction forming C3H8 and its reverse dissociation reaction in the temperature range 300-3000 K, k2(infinity)=2.41 x 10(-10) T(-0.34) exp(259/T) cm3 molecule(-1) s(-1) and k(-2)(infinity)=8.89 x 10(22) T(-1.67)exp(-46 037/T) s(-1), respectively, are also in good agreement with available experimental data.


Nitric oxide preconditioning regulates endothelial monolayer integrity via the heat shock protein 90-soluble guanylate cyclase pathway.
Large (pathological) amounts of nitric oxide (NO) induce cell injury, whereas low (physiological) NO concentrations often ameliorate cell injury. We tested the hypotheses that pretreatment of endothelial cells with low concentrations of NO (preconditioning) would prevent injury induced by high NO concentrations. Apoptosis, induced in bovine aortic endothelial cells (BAECs) by exposing them to either 4 mM sodium nitroprusside (SNP) or 0.5 mM N-(2-aminoethyl)-N-(2-hydroxy-2-nitrosohydrazino)-1,2-ethylenediamine (spermine NONOate) for 8 h, was abolished by 24-h pretreatment with either 100 microM SNP, 10 microM spermine NONOate, or 100 microM 8-bromo-cGMP (8-Br-cGMP). Repair of BAECs following wounding, measured as the recovery rate of transendothelial electrical resistance, was delayed by 8-h exposure to 4 mM SNP, and this delay was significantly attenuated by 24-h pretreatment with 100 microM SNP. NO preconditioning produced increased association and expression of soluble guanyl cyclase (sGC) and heat shock protein 90 (HSP90). The protective effect of NO preconditioning, but not the injurious effect of 4 mM SNP, was abolished by either a sGC activity inhibitor 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ) or a HSP90 binding inhibitor (radicicol) and was mimicked by 8-Br-cGMP. We conclude that preconditioning with a low dose of NO donor accelerates repair and maintains endothelial integrity via a mechanism that includes the HSP90/sGC pathway. HSP90/sGC may thus play a role in the protective effects of NO-generating drugs from injurious stimuli.


First experience of hematopoietic stem cell transplantation treatment of Shwachman-Diamond syndrome using unaffected HLA-matched sibling donor produced through preimplantation HLA typing.
The only proven cure for Shwachman-Diamond syndrome (SDS) bone marrow failure is allogeneic hematopoietic stem cell transplantation (HSCT). However HSCT with donors other than HLA-identical siblings is associated with high mortality and unfavorable prognosis. This paper presents the first experience of HSCT treatment of SDS using an unaffected HLA-identical sibling produced through preimplantation genetic diagnosis (PGD). The patient was a 6-year-old blood transfusion-dependent SDS baby girl with secondary myelodysplastic syndrome, for whom no HLA-identical donor was available. As a result of PGD, two unaffected HLA matched embryos were identified; one of them was randomly selected for transfer, resulting in a clinical pregnancy and birth of an apparently healthy child. The patient underwent allogeneic transplantation of cord blood hematopoietic stem cells, together with bone marrow from this sibling, resulting in complete hemopoietic recovery. The patient was no longer transfusion-dependent and had normal blood values 160 days after transplantation.


THE ROLE OF GENES OF LARGE EFFECT ON INBREEDING DEPRESSION IN MIMULUS GUTTATUS.
Severe inbreeding depression is routinely observed in outcrossing species. If inbreeding load is due largely to deleterious alleles of large effect, such as recessive lethals or steriles, then most of it is expected to be purged during brief periods of inbreeding. In contrast, if inbreeding depression is due to the cumulative effects of many deleterious alleles of small effect, then it will be maintained in the face of periodic inbreeding. Whether or not inbreeding depression can be purged with inbreeding in the short term has important implications for the evolution of mating systems and the probability that a small population will go extinct. In this paper I evaluate the extent to which the tremendous inbreeding load in a primarily outcrossing population of the wildflower, Mimulus guttatus, is due to alleles of large effect. To do this, I first constructed a large outbred "ancestral" population by randomly mating plants collected as seeds from a natural population. From this population I formed 1200 lines that were maintained by self-fertilization and single seedling descent: after five generations of selling, 335 lines had survived the inbreeding process. Selection during the line formation is expected to have largely purged alleles of large effect from the collection of highly inbred lines. Because alleles with minor effects on fitness should have been effectively neutral, the inbreeding depression due to this class of genes should have been unchanged. The inbred lines were intercrossed to form a large, outcrossed "purged" population. Finally, I estimated the fitness of outbred and selfed progeny from the ancestral and purged populations to determine the contribution of major deleterious alleles on inbreeding depression. I found that although the average fitness of the outcrossed progeny nearly doubled following purging, the limited decline in inbreeding depression and limited increase in inbred fitness indicates that alleles of large effect are not the principle cause of inbreeding depression in this population. In aggregate, the data suggest that lethals and steriles make a minority contribution to inbreeding depression and that the increased outbred fitness is due primarily to adaptation to greenhouse conditions.


Tests of conspecificity for closely related black fly (Diptera: Simuliidae) species of the Simulium striatum group in Thailand.
Four black fly species of the Simulium striatum species group have been recorded in Thailand. These species are morphologically highly similar in all developmental stages except for the number and arrangement of the pupal gill filaments. In this study, we used multiple characters sources, including morphology, cytology, molecular biology and ecology, to test the hypothesis of conspecificity for S. quinquestriatum (Shiraki), S. nakhonense Takaoka & Suzuki and S. chiangmaiense Takaoka & Suzuki. A molecular study based on the cytochrome c oxidase subunit I (COI) was unable to separate these taxa. In contrast, the elongation complex protein 1 (ECP1) sequences clearly differentiate S. quinquestriatum from S. chiangmaiense and S. nakhonense. However, the latter two taxa could not be differentiated based on molecular DNA sequences. Simulium chiangmaiense and S. nakhonense are also similar in the larval habitat characteristics and have undifferentiated polytene chromosome banding patterns. Morphological examination of the number and arrangement of the pupal gill filaments found a number of intermediate forms. Therefore, S. chiangmaiense and S. nakhonense are apparently the same biological species that is polymorphic for the number and arrangement of gill filaments. Thus, we synonymized S. chiangmaiense with S. nakhonense.


Robust Polyoxometalate/Nickel Foam Composite Electrodes for Sustained Electrochemical Oxygen Evolution at High pH.
The development of technologically viable electrodes for the electrochemical oxygen evolution reaction (OER) is a major bottleneck in chemical energy conversion. This article describes a facile one-step hydrothermal route to deposit microcrystals of a robust Dexter-Silverton polyoxometalate oxygen evolution catalyst, [Co6.8 Ni1.2 W12 O42 (OH)4 (H2 O)8 ], on a commercial nickel foam electrode. The electrode shows efficient and sustained electrochemical oxygen evolution at low overpotentials (360 mV at 10 mA cm-2 against RHE, Tafel slope 126 mV dec-1 , faradaic efficiency (96±5) %) in alkaline aqueous solution (pH 13). Post-catalytic analyses show no mechanical or chemical degradation and no physical detachment of the microcrystals. The results provide a blueprint for the stable "wiring" of POM catalysts to commercial metal foam substrates, thus giving access to technologically relevant composite OER electrodes.


Regulation of rat alpha-fetoprotein production by methionine during ethionine-hepatocarcinogenesis.
The levels of serum alpha-fetoprotein (AFP) in rats were determined during hepatocarcinogenesis with ethionine, and the effects of methionine administration on serum AFP elevation in these animals were studied with the aim of investigating regulatory mechanisms of AFP was observed 6 weeks following the start of feeding a diet containing 0.25% ethionine and again at the 22nd week of feeding, when a well-differentiated hepatoma had already developed. These biphasic elevations of serum AFP concentrations in rats fed a 0.25% ethionine-containing diet decreased abruptly an significantly following a change to the basal diet either supplemented with or without 0.7% methionine. The possibility that regulation of AFP production in these rats may correlate with methionine metabolisms is discussed on the basis of the experimental data obtained.


In vivo optical spectroscopy detects radiation damage in brain tissue.
Magnetic resonance imaging abnormalities in malignant brain tumors after irradiation may represent either recurrent tumor or radiation injury. Optical spectroscopy may represent a novel technique to identify radiation damage in brain tissues and to differentiate contrast-enhancing lesions from recurrent tumor. Fluorescence and diffuse reflectance spectra were acquired from 90 patients: 15 undergoing surgical resection for presumed recurrent tumor after radiation therapy, 15 with epilepsy and hippocampal sclerosis, and 60 with tumors who had not received irradiation. Optical spectra were acquired from 6 to 10 sites and were compared with a biopsy obtained from beneath the optical spectroscopy probe; the data then were classified by a neuropathologist blinded to the spectroscopy data. A probe for the intraoperative collection of diffuse reflectance and fluorescence spectra was used. Thirteen of 15 patients (29 of 129 spectra) with previous irradiation showed a unique spectral feature characterized by a fluorescence peak centered at 500 nm (F500). All biopsy specimens showing histopathological signs of radiation injury had the F500 on their corresponding spectra (18 of 18). The F500 was identified in another 10% (11 of 111 spectra) of samples with previous irradiation but no histologically identifiable signs of radiation damage. The F500 was never seen in the normal temporal lobe of epilepsy patients with hippocampal sclerosis (0 of 105) and was seen in only 1.5% of tumor patients who did not undergo previous irradiation (6 of 433). Optical spectroscopy detects radiation damage in brain tissues. The F500 spectral peak may allow accurate selection of tissues for biopsy in evaluating patients with new, contrast-enhancing lesions in the setting of previous irradiation.


Direct determination of the intracellular oxidation state of plutonium.
Microprobe X-ray absorption near edge structure (μ-XANES) measurements were used to determine directly, for the first time, the oxidation state of intracellular plutonium in individual 0.1-μm(2) areas within single rat pheochromocytoma cells (PC12). The living cells were incubated in vitro for 3 h in the presence of Pu added to the media in different oxidation states (Pu(III), Pu(IV), and Pu(VI)) and in different chemical forms. Regardless of the initial oxidation state or chemical form of Pu presented to the cells, the XANES spectra of the intracellular Pu deposits were always consistent with tetravalent Pu even though the intracellular milieu is generally reducing.


MicroRNA-330 Directs Downregulation of the GABABR2 in the Pathogenesis of Pancreatic Cancer Pain.
Pancreatic cancer is one of the most aggressive and deadly malignancies with a very poor prognosis. Pancreatic cancer-induced visceral pain is very common and is generally presented among the initial symptoms in patients; such pain is strongly associated with poor quality of life, impaired functional activity, and decreased survival. However, the principal neurobiological mechanisms of pain caused by pancreatic cancer have not been fully elucidated. Accumulating studies have shown that miRNAs play a major role in chronic pain by suppressing key molecules involved in nociception. In the present study, we report that microRNA (miR)-330 is highly expressed in the spinal dorsal horn (SDH) of nude mice with pancreatic cancer pain. Mimicking pancreatic carcinoma-induced SDH miR-330 upregulation by microinjection of miR-330 mimic into the SDH significantly induced abdominal mechanical allodynia in normal nude mice. Additionally, we found that the expression of GABABR2 was significantly decreased in the SDH of nude mice with pancreatic cancer pain and was regulated directly by miR-330 both in vitro and in vivo. Furthermore, inhibition of miR-330 rescued the expression of GABABR2 and alleviated pancreatic carcinoma-induced abdominal pain hypersensitivity in nude mice with pancreatic carcinoma. These results show that miR-330 participates in the genesis of pancreatic carcinoma-induced pain hypersensitivity by inhibiting GABABR2 expression in the SDH and might be a potential therapeutic target for pancreatic cancer pain.


[Anesthetic management for gastrectomy of a patient after coronary artery bypass graft with gastroepiploic artery].
We report anesthetic management of an 80-year-old man who had received coronary artery bypass graft with the gastroepiploic artery 5 years before the present gastrectomy. Preoperative angiography did not show patency of the grafted gastroepiploic artery. He underwent partial distal gastrectomy under general anesthesia with isoflurane in oxygen-enriched air combined with epidural block. The gastroepiploic artery was severed after temporary clamping which did not produce evidence of myocardial ischemia. There was no postoperative cardiovascular event after the surgery.


Inhibition of Helicobacter pylori adhesion to human gastric adenocarcinoma epithelial cells by acidic polysaccharides from Artemisia capillaris and Panax ginseng.
Helicobacter pylori specifically adheres to host cells, mainly based on carbohydrate-mediated cell-cell interactions. Previously, we investigated the anti-adhesive effect of polysaccharide fractions from Artemisia capillaris and Panax ginseng, using hemagglutination and enzyme-linked glycosorbent assays. In the present study, each active polysaccharide fraction was further purified, resulting in a single peak (fraction F2) using gel filtration FPLC, in which no protein content was detectable. Using scanning electron microscopy, we examined the inhibitory effects of these polysaccharides on the attachment of H. pylori to the human gastric adenocarcinoma epithelial cell line. The bacterial attachment to the cell line was inhibited by these polysaccharides in the range of the concentrations studied (0.2 - 2.8 mg/mL), showing their minimum inhibitory concentration at as low as 0.2 mg/mL. The bacterial binding was inhibited more effectively by P. ginseng polysaccharides, than by those from A. capillaris. The purified polysaccharides contain similar sugar compositions and have high amounts of uronic acids. Our results suggest that acidic carbohydrates may play an important role in the inhibitory activity on H. pylori adhesion to host cells and that our established purification protocol can be applied to obtain active acidic polysaccharides from plant sources.


Orthogonal functionalization of cyclopenta[hi]aceanthrylenes.
A synthetic strategy to prepare 2,7- or 4,9-functionalized cyclopenta[hi]aceanthrylenes that are capable of Suzuki cross-coupling reactions is demonstrated. This method has been utilized to create a series of thiophene derivatized compounds that were subsequently used to investigate the role of substitution pattern on the photophysical and electronic properties of cyclopenta[hi]aceanthrylenes. The orthogonal functionalization provides access to unique substitution patterns (e.g., cruciform-like architectures) and materials with small optical band gaps (1.22-1.97 eV).


[Characterization of intertype specific epitopes on adenoviruses hexon].
To characterize the intertype epitopes on human adenovirus (HAdV) hexon. Based on computerized analysis on adenoviruses sequence of genomic alignment, antigenicity prediction and 3-D structure characteristics of hexon subunit, several peptides of hexon of adenoviruses were chosen to be synthesized or recombinant proteins of the hexon were expressed in E. coli by use of PGEX-5X. To identify the existence of intertype epitopes, the antisera raised with synthetic peptides or purified recombinant proteins were analyzed with Western blot and immunofluorescent assay. The results of Western blot indicated that both peptide and recombinant antibodies showed specific reactivities with hexons of HADv-3, 4, 7 individually. Meanwhile, typical stain of immunofluorescence was found on HeLa cells infected with these HAdV by incubation with peptide as well as recombinant antibodies. Also, antibodies raised against peptide recognized the recombinant hexon protein in which a corresponding region of peptides was covered. Most of the predicted intertype epitopes of HAdV hexon wer e exclusively found in synthetic peptides and recombinant proteins. These intertype epitopes showed to be continuous and sequential which could be employed for development of antibodies of diagnostic use.


Tissue Engineering and Regenerative Medicine: The Promise, the Challenges, the Future.
Medical researchers increasingly regard tissue engineering and regenerative medicine as potential game changers when it comes to repairing damage from disease or injury and restoring function. To understand the progress made and challenges ahead for this combined field, IEEE Pulse sought out two experts: David F. Williams, former global president (2012-2015) of the Tissue Engineering and Regenerative Medicine International Society, and Roderic I. Pettigrew, founding director of the National Institute of Biomedical Imaging and Bioengineering (NIBIB) at the National Institutes of Health (NIH) [1].


Computerised working memory training in healthy adults: a comparison of two different training schedules.
This study compared a high intensity working memory training (45 minutes, 4 times per week for 4 weeks) with a distributed training (45 minutes, 2 times per week for 8 weeks) in middle-aged, healthy adults. The aim was to clarify whether a computerised working memory training is effective and whether intensity of training influences training outcome. To evaluate the efficacy and possible transfer effects, a neuropsychological test battery assessing short- and long-term memory, working memory, executive functions and mental speed was applied at baseline and at retest. Our results indicate that the distributed training led to increased performance in all cognitive domains when compared to the high intensity training and the control group without training. The most significant differences revealed by interaction contrasts were found for verbal and visual working memory, verbal short-term memory and mental speed. These results support the hypothesis that cognitive enhancement by cognitive intervention is effective in healthy individuals, and that a distributed training schedule is superior to a high intensity intervention.


Advances in targeted therapy for anaplastic thyroid carcinoma.
Anaplastic thyroid carcinoma (ATC) is a highly malignant and aggressive thyroid malignancy with rapid onset and poor prognosis. There is no effective treatment for ATC yet. Molecular targeted therapy provides a new idea for ATC treatment. Tyrosine kinase inhibitor lenvatinib has potential in treating ATC patients with favorable efficacy in clinical trials. The effectiveness of the v-raf murine sarcoma viral oncogene homologue B1 () gene inhibitor dabrafenib in combination with trametinib for the treatment of positive ATC patients has been demonstrated in clinical trials. The has proposed dabrafenib in combination with trametinib as the preferred modality for the treatment of patients with positive ATC. The immune checkpoint inhibitor pembrolizumab can be applied to treat thyroid cancer with high tumor mutational load and may be considered as the preferred modality for the treatment of ATC patients with high programmed death ligand-1 expression. The mammalian target of rapamycin pathway inhibitors, peroxisome proliferators-activated receptor γ agonists, endothelial growth factor receptors-targeting monoclonal antibody cetuximab and novel vascular blocker fosbretabulin are still in the clinical research stage, which are expected to provide new directions for the development of novel targeted drugs. This article reviews the current research progress on targeted drugs for the treatment of ATC.


Placental Proteomics Reveal Insights into Fetal Alcohol Spectrum Disorders.
Fetal alcohol spectrum disorders (FASD) describe many of the well-known neurodevelopmental deficits afflicting children exposed to alcohol in utero. The effects of alcohol on the maternal-fetal interface, especially the placenta, have been less explored. We herein hypothesized that chronic binge alcohol exposure during pregnancy significantly alters the placental protein profile in a rat FASD model. Pregnant rats were orogastrically treated daily with alcohol (4.5 g/kg, gestational day [GD] 5 to 10; 6.0 g/kg, GD 11 to 19) or 50% maltose dextrin (isocalorically matched pair-fed controls). On GD 20, placentae were collected, flash-frozen, and stored until tissues were homogenized. Protein lysates were denatured, reduced, captured on a 10-kDa spin filter, and digested. Peptides were eluted, reconstituted, and analyzed by a Q Exactive™ Hybrid Quadrupole-Orbitrap™ mass spectrometer. Mass spectrometry (MS) analysis identified 2,285 placental proteins based on normalized spectral counts and 2,000 proteins by intensity-based absolute quantification. Forty-five placental proteins were significantly (p < 0.05) altered by gestational alcohol exposure by both quantification approaches. These included proteins directly related to alcohol metabolism; specific isoforms of alcohol dehydrogenase and aldehyde dehydrogenase were up-regulated in the alcohol group. Ingenuity analysis identified ethanol degradation as the most significantly altered canonical pathway in placenta, and fetal/organ development as most altered function, with increased risk for metabolic, neurological, and cardiovascular diseases. Physiological roles of the significantly altered proteins were related to early pregnancy adaptations, implantation, gestational diseases, fetal organ development, neurodevelopment, and immune functions. We conclude that the placenta is a valuable organ not only to understand FASD etiology but it may also serve as a diagnostic tool to identify novel biomarkers for detecting the outcome of fetal alcohol exposure. Placental MS analysis can offer sophisticated insights into identifying alcohol metabolism-related enzymes and regulators of fetal development.


The Influence of Piper sarmentosum Extract on Growth Performance, Intestinal Barrier Function, and Metabolism of Growing Chickens.
In the poultry industry, there is an urgent need to evaluate and introduce natural, effective, and safe alternatives for synthetic antibiotics, which have been banned in most countries. The present study aimed to investigate the effects of dietary supplementation with Piper sarmentosum extract (PSE) on the growth performance, intestinal barrier function, and metabolism of growing chickens. A total of 400 seven-day-old female chicks were randomly assigned to four dietary treatments, each of which consisted of five replicates and twenty birds each. The four experimental treatments were fed a basal diet containing 0, 100, 200, and 300 mg PSE/kg (BC, PSE1, PSE2, and PSE3 groups), respectively. The experiment lasted for 28 days. The results showed that dietary supplementation with PSE had no significant effects on the final body weight, average daily gain (ADG), average daily feed intake (ADFI), and the ratio of ADFI to ADG (F/G) (p > 0.05). Compared with the BC group, dietary supplementation with 200-300 mg/kg PSE increased the villus height in the jejunum and ileum of chickens (p < 0.05). The PSE-treated groups significantly increased the mRNA expression of Occludin, ZO-1, and Claudin-1 in the ileal mucosa of chickens (p < 0.05). In addition, a significant decrease in ileal TNF-α and IL-8 mRNA expression (p < 0.05) and a significant increase in IL-22 (p < 0.05) were observed in the PSE2 treatment compared to the BC group. Additionally, three gut metabolites (i.e., citrate, isocitrate, and spermine) showed significant differences among treatments (p < 0.05) and were involved in the tricarboxylic acid (TCA) cycle, the transfer of acetyl groups into mitochondria, and spermidine and spermine biosynthesis, respectively. In conclusion, the findings obtained here indicate that supplemental PSE can enhance the anti-inflammatory capacity and intestinal mucosal barrier function of chickens.


Solitary myofibroma preceding the development of multicentric myofibromatosis: A report of two cases with surveillance recommendations.
Infantile myofibroma is the most common fibrous tumor of infancy. Despite the frequency of these tumors, the natural history is incompletely understood. We present two cases with a unique pattern of disease: solitary myofibromas with subsequent progression to diffuse myofibromatosis. Given the variable spectrum of disease and the corresponding difference in morbidity and potential mortality based on the extent of disease, we propose surveillance recommendations.


Modeling and optimal regulation of erythropoiesis subject to benzene intoxication.
Benzene (C(6)H(6)) is a highly flammable, colorless liquid. Ubiquitous exposures result from its presence in gasoline vapors, cigarette smoke, and industrial processes. Benzene increases the incidence of leukemia in humans when they are exposed to high doses for extended periods; however, leukemia risks in humans subjected to low exposures are uncertain. The exposure-dose- response relationship of benzene in humans is expected to be nonlinear because benzene undergoes a series of metabolic transformations, detoxifying and activating, resulting in various metabolites that exert toxic effects on the bone marrow. Since benzene is a known human leukemogen, the toxicity of benzene in the bone marrow is of most importance. And because blood cells are produced in the bone marrow, we investigated the effects of benzene on hematopoiesis (blood cell production and development). An age-structured model was used to examine the process of erythropoiesis, the development of red blood cells. This investigation proved the existence and uniqueness of the solution of the system of coupled partial and ordinary differential equations. In addition, we formulated an optimal control problem for the control of erythropoiesis and performed numerical simulations to compare the performance of the optimal feedback law and another feedback function based on the Hill function.


The Multi-Faced Extracellular Vesicles in the Plasma of Chronic Kidney Disease Patients.
Extracellular vesicles (EVs) are membrane-enclosed nanoparticles released by most cells in body fluids and extracellular matrix. They function as signal transducers in intercellular communication, contributing to the maintenance of cell and tissue integrity. EVs biogenesis is deregulated in various pathologies, in structural and functional connection to the pathophysiology of donor cells. Consequently, EVs are considered diagnostic and monitoring factors in many diseases. Despite consensus as to their activity in promoting coagulation and inflammation, there is evidence suggesting protective roles for EVs in stress states. Chronic kidney disease (CKD) patients are at high risk of developing cardiovascular defects. The pathophysiology, comorbidities, and treatment of CKD may individually and in synergy affect extracellular vesiculation in the kidney, endothelium, and blood cells. Oxidative and mechanical stresses, chronic inflammation, and deregulation of calcium and phosphate homeostasis are established stressors of EV release. EVs may affect the clinical severity of CKD by transferring biological response modifiers between renal, vascular, blood, and inflammatory cells. In this Review, we focus on EVs circulating in the plasma of CKD patients. We highlight some recent advances in the understanding of their biogenesis, the effects of dialysis, and pharmacological treatments on them and their potential impact on thrombosis and vascular defects. The strong interest of the scientific community to this exciting field of research may reveal hidden pieces in the pathophysiology of CKD and thus, innovative ways to treat it. Overcoming gaps in EV biology and technical difficulties related to their size and heterogeneity will define the success of the project.


Antiplatelet agents for chronic kidney disease.
Antiplatelet agents are widely used to prevent cardiovascular events. The risks and benefits of antiplatelet treatment may be different in people with chronic kidney disease (CKD) for whom occlusive atherosclerotic events are less prevalent, and bleeding hazards might be increased. To summarise the effects of antiplatelet treatment (antiplatelet agent versus control or other antiplatelet agent) for the prevention of cardiovascular and adverse kidney outcomes in individuals with CKD. In January 2011 we searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and the Cochrane Renal Group's Specialised Register without language restriction. We selected randomised controlled trials of any antiplatelet treatment versus placebo or no treatment, or direct head-to-head antiplatelet agent studies in people with CKD. Studies were included if they enrolled participants with CKD, or included people in broader at-risk populations in which data for subgroups with CKD could be disaggregated. Two authors independently extracted data from primary study reports and any available supplementary information for study population, interventions, outcomes, and risks of bias. Risk ratios (RR) and 95% confidence intervals (CI) were calculated from numbers of events and numbers of participants at risk which were extracted from each included study. The reported RRs were extracted where crude event rates were not provided. Data was pooled using the random-effects model. We included 50 studies, enrolling 27,139 participants; 44 studies (21,460 participants) compared an antiplatelet agent with placebo or no treatment, and six studies (5679 participants) directly compared one antiplatelet agent with another. Compared to placebo or no treatment, antiplatelet agents reduced the risk of myocardial infarction (17 studies; RR 0.87, 95% CI 0.76 to 0.99), but not all-cause mortality (30 studies; RR 0.93, 95% CI 0.81 to 1.06), cardiovascular mortality (19 studies; RR 0.89, 95% CI 0.70 to 1.12) or stroke (11 studies; RR 1.00, 95% CI 0.58 to 1.72). Antiplatelet agents increased the risk of major (27 studies; RR 1.33, 95% CI 1.10 to 1.65) and minor bleeding (18 studies; RR 1.49, 95% CI 1.12 to 1.97). In terms of dialysis access outcomes, antiplatelet agents reduced access thrombosis or patency failure but had no effect on suitability for dialysis. Meta-regression analysis indicated no differences in the relative benefit or harms of treatment (risk of all-cause mortality, myocardial infarction, or major bleeding) by type of antiplatelet agent or stage of CKD. Limited data were available for direct head-to-head comparisons of antiplatelet drugs, treatment in kidney transplant recipients, primary prevention, or risk of ESKD. Antiplatelet agents reduce myocardial infarction but increase major bleeding. Risks may outweigh harms among people with low annual risks of cardiovascular events, including those with early stages of CKD who do not have clinically-evident occlusive cardiovascular disease.


Severe preschool asthmatics have altered cytokine and anti-viral responses during exacerbation.
Preschool asthma/recurrent wheeze is a heterogeneous condition. Different clinical phenotypes have been described, including episodic viral wheeze (EVW), severe intermittent wheeze (SIW), and multiple-trigger wheeze (MTW). To compare clinical, viral, and inflammatory/immune profiling at exacerbation between MTW, SIW, and EVW phenotypes. Multicenter, prospective, observational cohort (VIRASTHMA-2). Children (1-5 years) with preschool asthma were enrolled during hospitalization for a severe exacerbation. History and anamnestic data, plasma, and nasal samples were collected at exacerbation (T1) and at steady state, 8 weeks later (T2), and sputum samples were collected at T1. A total of 147 children were enrolled, 37 (25%) had SIW, 18 (12.2%) EVW, and 92 (63%) MTW. They were atopic (47%), exposed to mold (22%) and cigarette smoke (50%), and prone to exacerbations (≥2 in the previous year in 70%). At exacerbation, at least one virus was isolated in 94% and rhinovirus in 75%, with no difference between phenotypes. Children with MTW and SIW phenotypes displayed lower plasma concentrations of IFN-γ (P = .002), IL-5 (P = .020), TNF-α (P = .038), IL-10 (P = .002), IFN-β (P = .036), and CXCL10 (P = .006) and lower levels of IFN-γ (P = .047) in sputum at exacerbation than children with EVW. At T2, they also displayed lower plasma levels of IFN-γ (P = .045) and CXCL10 (P = .013). Among preschool asthmatic children, MTW and SIW, prone to exacerbations, display lower systemic levels of Th1, Th2 cytokines, pro- and anti-inflammatory cytokines, and antiviral responses during severe virus-induced exacerbation.


In vitro modeling of spinal anesthesia. A digital video image processing technique and its application to catheter characterization.
Maldistribution of intrathecal local anesthetic has recently been implicated as a contributor to neurotoxic injury. In vitro modeling can be used to understand the distribution of anesthetic agents within the subarachnoid space. We describe an in vitro modeling technique that uses digital video image processing and its application to catheter injection of local anesthetic. A clear plastic model of the subarachnoid space, including a simulated spinal cord and cauda equina, was filled with lactated Ringer's solution. Phthalocyanine blue dye of known concentration was injected into the model through small-bore (28-G) and large-bore (18-G) catheters. Injections were performed at a variety of controlled rates and sacral catheter positions, and the propagation of dye throughout the model was recorded on videotape, digitized by computer, and converted to a two-dimensional image of dye concentration. A subset of data was compared with results obtained from spectrophotometric analysis. There was a strong correlation (r = 0.98) between data obtained with analysis by digital video image processing and those obtained spectrophotometrically. Catheter size, catheter angle, and injection rate significantly influenced the distribution and peak concentration of simulated anesthetic. No major differences in distribution or peak concentration were observed with the two types of 28-G catheters. The digital video image processing technique can be used to quantify anesthetic distribution rapidly within a model of the subarachnoid space without disturbing the distribution. The current results demonstrate a strong dependence of anesthetic distribution on catheter angle, catheter size, and injection rate. Comparisons between 28-G catheters suggest that the difference in reported incidence of cauda equina syndrome associated with different 28-G catheters cannot be explained on the basis of differences in anesthetic distribution.


The laminin-derived peptide C16 regulates GPNMB expression and function in breast cancer.
Breast cancer is an important public health problem, and its progression may be related to the extracellular matrix (ECM), which acts as a structural scaffold and instruction source for neoplastic cells. Laminins are ECM proteins regulating tumor biology. The laminin-derived peptide C16 regulates different properties of tumor cells. Here we analyzed C16-induced differential gene expression in MDA-MB-231 breast cancer cells. MCF-10A normal-like breast cells served as control. Among different cancer-related genes, C16 induced overexpression of GPNMB. This gene encodes a transmembrane protein GPNMB (glycoprotein non-metastatic B), involved with malignant phenotype of breast cancer cells. Immunoblot validated microarray results. To correlate gene and protein expression with cellular function, we investigated whether C16 would regulate invasion in breast cancer cells. siRNA experiments strongly suggested that C16 and GPNMB cooperate to regulate invasion of highly aggressive MDA-MB-231 cancer cells. We addressed regulatory mechanisms involved in C16-mediated increase of GPNMB protein levels in MDA-MB-231 cells, and observed that C16 stimulates β1 integrin and Src phosphorylation. Furthermore, Src inhibition decreases peptide-induced GPNMB expression levels. To contextualize in vivo our results in vitro, we addressed GPNMB immunostaining in breast cancer human tissue microarrays. Quantitative immunohistochemistry showed that GPNMB is significantly more expressed in breast cancer compared to normal tissue. We concluded that laminin-derived peptide C16 regulates gene and protein expression of GPNMB in breast cancer cells. C16 and GPNMB may cooperate to regulate invasion of highly aggressive MDA-MB-231 cells, probably through Src signaling. GPNMB presented increased expression in breast cancer in vivo compared to normal breast tissue.


Falciparum malaria as a cause of fever in adult travellers returning to the United Kingdom: observational study of risk by geographical area.
The probability that a returned traveller with a history of fever has malaria is likely to vary by geographical area, but this has not been quantified in travellers. To collect data on prevalence of malaria in outpatients returning with a fever or history of fever from malaria-endemic countries, at the point of presentation for a malaria test. Observational retrospective study. Consecutive patients presenting to an unselected 'walk-in' clinic for returned travellers. Of 2867 patients meeting inclusion criteria, 337 (11.8%) had malaria, 89.5% originating in sub-Saharan Africa. Of travellers returning from sub-Saharan Africa excluding South Africa with fever/history of fever, 291/1497 had malaria (19.4%, 95% CI 17-21%). A high proportion was visiting friends and relatives. In those from other areas the proportions were: 16/707 (2.3%, 95% CI 1.5-3.8) from Indian subcontinent/Southeast Asia; 2/143 (1.4%) from Southern America; 4/129 (3.1%) from South Africa; 1/44 (2.3%) from North Africa; and 8/41 (19.5%) from Oceania. Compared to other malaria-endemic regions, African travel gave an adjusted odds ratio of 7.8 (95% CI 5.4-11.2, P < 0.0001). Only 45.1% of malaria cases had a fever (> or =37.5 degrees C) at the time of presentation. Only 3% of all diagnoses of malaria had no history of fever. In 28% of cases parasite count increased in the initial 24 h of antimalarial treatment. The likelihood that a patient with fever returning from Africa has malaria is high (around 1 in 5), and is significantly lower from other areas. Absence of fever at presentation does not exclude malaria.


Flying and swimming animals cruise at a Strouhal number tuned for high power efficiency.
Dimensionless numbers are important in biomechanics because their constancy can imply dynamic similarity between systems, despite possible differences in medium or scale. A dimensionless parameter that describes the tail or wing kinematics of swimming and flying animals is the Strouhal number, St = fA/U, which divides stroke frequency (f) and amplitude (A) by forward speed (U). St is known to govern a well-defined series of vortex growth and shedding regimes for airfoils undergoing pitching and heaving motions. Propulsive efficiency is high over a narrow range of St and usually peaks within the interval 0.2 < St < 0.4 (refs 3-8). Because natural selection is likely to tune animals for high propulsive efficiency, we expect it to constrain the range of St that animals use. This seems to be true for dolphins, sharks and bony fish, which swim at 0.2 < St < 0.4. Here we show that birds, bats and insects also converge on the same narrow range of St, but only when cruising. Tuning cruise kinematics to optimize St therefore seems to be a general principle of oscillatory lift-based propulsion.


Bis(tetraethylammonium) tetraiodozincate at 150 and 301 K.
The refinements described here for (NEt(4))[ZnI(4)] completely confirm the results previously obtained for the isostructural tetrabromocadmate at room temperature [Geselle & Fuess (1994). Acta Cryst. C50, 1582-1585]. Here again, isolated MX(4) (M = Zn and X = I) tetrahedra are accompanied by two cations in a 'swastika' conformation and a third in a virtually planar trans conformation. One of the former cations is particularly disordered.


[Efficacy of chloroquine in treatment of non-complicated malaria with Plasmodium falciparum in children at the San Pedro dispensary in Côte d'Ivoire].
A survey has been carried out in south-west of Côte d'Ivoire in order to study chloroquine resistance in treatment of malaria according to 14 days protocol of WHO (World Health Organisation) (1996) for evaluation of antimalarial drugs activity; 63 children, aged from 6 months to 15 years and suffering from noncomplicated malaria due to Plasmodium falciparum, received by oral way 25 mg/kg of chloroquine over three days (10-10-5). During the survey, they were subjected to a clinic and parasitologic (thick and thin blood film) follow up. We obtained, for 51 children (81%), a satisfactory clinical answer, for 8 children (13%) an early therapeutic failure and for the other 4 (6%) a late therapeutic failure. Moreover, we obtained 40% of failure in children of less than 24 months old, 25% between 24 months and 59 months and 7% beyond 6 years old.


Hand Assessment for Elderly People in the Community.
Hand conditions are common in elderly persons. To assess the prevalence of common hand conditions in elderly persons in a community setting, specifically osteoarthritis of the hand, trigger finger, and carpal tunnel syndrome. The elderly persons were recruited from community groups for elderly persons. Data collection included participants' demographic and clinical data; quick disability, arm, shoulder, and hand (QuickDASH) questionnaire; and presence of hand conditions. Of the 55 elderly persons recruited, almost a third of them presented with a hand condition (n = 17, 30.8%). Hand conditions were more common in females (39% in females, 7% in males; χ = 4.97, p = .04). Quick-DASH scores were higher in those with hand conditions, indicating lower levels of function (greater disability) (t =-4.61, p = .002). Most elderly persons did not seek medical attention for their hand condition until the late stages. Nurses can play an important role in providing community hand assessment, education on hand symptoms, information about available treatment, and adaptive approaches to maximize functioning.


[Anti-tumor effect and mechanism of action of the tumor necrosis factor (TNF)].
TNF is cytokine derived from macrophages and shows much promise for use in cancer therapy because of its marked antitumor effects and its high specificity to tumors. The clinical application (Phase I-II) of TNF has been started because human recombinant TNF (rH-TNF) can be produced on a large scale. In spite of notable antitumor effects, little is known concerning the mechanism of its cytotoxic action. In this article, the antitumor effects of rH-TNF against human and murine tumors, the mechanism of its action and the synergistic effects of rH-TNF in combination with IFN-gamma, various anticancer drugs or with hyperthermia are reviewed.


The clinician's role in environmental protection.
The clinically working medical doctors are insufficiently trained in epidemiology and community medicine. They are, therefore, not sufficiently aware of health related environmental factors. They cannot avoid the difficulties of generalizing clinical observations because of small numbers and the long latency period in chronic disease evolution. As centralization of treatment is not generally possible we must improve our systems for registration of environmentally induced disease and health monitoring of the population. Finally, the clinicians should be more concerned with follow-up of administrative disease preventing actions.


Halogen-bonding mediated stepwise assembly of gold nanoparticles onto planar surfaces.
In this study halogen bonding (XB) is used as the driving force for the noncovalent assembly of gold nanoparticles (AuNPs) on silicon and quartz substrates functionalized with organic monolayers. The AuNPs are functionalized with XB-donor ligands, whereas the monolayers have pyridine groups as XB-acceptors. The surface-confined systems are formed by iteratively exposing the monolayers to solutions of organic cross-linkers having 2-4 pyridine groups and functionalized AuNPs. UV-vis spectroscopy, atomic force microscopy (AFM), and scanning electron microscopy (SEM) reveal how the structure of the resulting surface-bound assemblies are controlled by (i) the properties of the monolayers, (ii) the molecular structure and the number of XB binding sites of the organic cross-linker, and (iii) the number of functionalized AuNP and cross-linker deposition steps. Moreover, these structures exhibit surface-enhanced Raman scattering and significant changes are observed in the morphology of some of the surface-bound assemblies upon aging.


Glucosylglycerate biosynthesis in the deepest lineage of the Bacteria: characterization of the thermophilic proteins GpgS and GpgP from Persephonella marina.
The pathway for the synthesis of glucosylglycerate (GG) in the thermophilic bacterium Persephonella marina is proposed based on the activities of recombinant glucosyl-3-phosphoglycerate (GPG) synthase (GpgS) and glucosyl-3-phosphoglycerate phosphatase (GpgP). The sequences of gpgS and gpgP from the cold-adapted bacterium Methanococcoides burtonii were used to identify the homologues in the genome of P. marina, which were separately cloned and overexpressed as His-tagged proteins in Escherichia coli. The recombinant GpgS protein of P. marina, unlike the homologue from M. burtonii, which was specific for GDP-glucose, catalyzed the synthesis of GPG from UDP-glucose, GDP-glucose, ADP-glucose, and TDP-glucose (in order of decreasing efficiency) and from d-3-phosphoglycerate, with maximal activity at 90 degrees C. The recombinant GpgP protein, like the M. burtonii homologue, dephosphorylated GPG and mannosyl-3-phosphoglycerate (MPG) to GG and mannosylglycerate, respectively, yet at high temperatures the hydrolysis of GPG was more efficient than that of MPG. Gel filtration indicates that GpgS is a dimeric protein, while GpgP is monomeric. This is the first characterization of genes and enzymes for the synthesis of GG in a thermophile.


Heterotypic cellular cooperation in gut morphogenesis and differentiation.
The development of the gastrointestinal tract, like that of other organs, results from the association of intrinsic genetic endowment, endogenous regulatory mechanisms and environmental influences. The present chapter emphasizes the role of epithelial-mesenchymal interactions during development and crypt-villus migration. Arguments are given as to the role of basement membrane molecules as mediators for these cell interactions. Differential developmental expression of the various extracellular matrix components, which precedes the onset of differentiation markers, suggests that each of these molecules assumes a specific task. Yet, much work still remains to be done before knowing exactly how transfer of morphogenetic signals between epithelial and mesenchymal tissues occurs.


Quercetin mediated lifespan extension in Caenorhabditis elegans is modulated by age-1, daf-2, sek-1 and unc-43.
The nematode Caenorhabditis elegans responds to flavonoid-rich diets with improved health and longevity. The precise mechanism(s) responsible for this remains to be identified, but is believed to be linked to the highly antioxidative properties of flavonoids. This study provides a dissection of lifespan modulation by the flavonoid quercetin. In detail, quercetin was shown not to act as a simple antimicrobial agent or exclusively via radical scavenging capacities. Likewise, lifespan extension had no effect on reproduction and body length. Furthermore, neither a caloric restriction mimetic nor a sirtuin (sir-2.1) dependence was identified as a likely mode of action. However, four genes were pinpointed to be required for the quercetin derived lifespan extension, namely age-1, daf-2, unc-43 and sek-1. The latter two have, to date, not been linked to quercetin-mediated lifespan extension.


Rapid purification of lysozyme by mixed-mode adsorption chromatography in stirred fluidized bed.
The commercial STREAMLINE Direct HST adsorbent was employed to investigate the adsorption characteristics of lysozyme in complex chicken egg white (CEW). The effects of operating parameters, including adsorption pH, ionic strength, and hydrophobicity of liquids on binding capacity, were examined using a well-mixed contactor. To determine the elution strategy, the experiments were carried out in a small packed bed. The lysozyme was completely eluted by 0.5 M NaCl in 40 mM carbonate buffer (pH 12) at a high liquid velocity of 200 cm/h. The effect of rotating speed on fluidization characteristics was further investigated by using a stirred fluidized bed process. Smoother fluidization was observed when the rotating speed reached 200 rpm and lysozyme was directly recovered from highly viscous CEW in a single step with a high yield of 94.3% and a purification factor of 15.7.


Role of anisomorphic DNA conformations in the negative regulation of a herpes simplex virus type 1 promoter.
The a sequence is a bifunctional element in the herpes simplex virus type 1 (HSV-1) genome which possesses both the signals required for the cleavage and encapsidation of replicated viral DNA and the promoter-regulatory sequences for the gene encoding the viral neurovirulence factor ICP34.5. Since the ICP34.5 promoter lacks features that are characteristic of most HSV-1 promoters, including a canonical TATA box, an initiator element, and upstream binding sites for host cell transcription factors, a mutational analysis was undertaken to identify the cis-acting elements which mediate transcription of this gene in transient transfection assays. A deletion derivative containing sequences just 83 nucleotides upstream of the second of two cap sites was found to exhibit full promoter activity. However, the presence of either of two far upstream regions, which coincided with the DR2 and DR6 tandem GC-rich repeat arrays, acted to abrogate transcriptional activity both in this segment of the ICP34.5 promoter and in a heterologous promoter construct. The DR2 and DR6 repeat arrays each possessed an unwound S1 nuclease-sensitive DNA conformation (anisomorphic DNA) whose formation was shown to be critical for mediating this transcriptional repression effect. Moreover, results from in vivo titration experiments suggested the existence of a cellular protein(s) which can mediate transcriptional repression in the ICP34.5 promoter by specifically interacting with the single-stranded regions of these tandem repeat arrays. Such DNA conformation-dependent transcriptional silencing appears to represent a novel mechanism of gene regulation in the HSV-1 life cycle.


Antinociceptive Effect of the Citrus Flavonoid Eriocitrinon Postoperative Pain Conditions.
Postoperative pain remains a major clinical problem as there are limited analgesic strategies that have been proven to be effective in preventing and relieving this type of pain. Natural products, including flavonoids, have distinct pharmacological properties and play an important role in the discovery of analgesic drugs. In this study, the flavonoid eriocitrin (eriodictyol 7-O-rutinoside), which is the main flavonoid in lemon fruit (Citrus limon), was mechanistically investigated for its prospective antinociceptive effect in a mouse model of postoperative pain. The antinociceptive property was evaluated by utilizing both tonic (acetic acid-induced writhing behavior) and phasic (hot-plate) nociception modalities. The hindpaw incisional surgery was performed and hyperalgesia was assessed using von Frey filaments. The tested doses of eriocitrin significantly attenuated (P<0.01, P<0.001) the chemically-induced tonic visceral nociception (5, 10, 15, and 30 mg/kg) and acute phasic thermal nociception (10, 15, and 30 mg/kg). A significant dose-dependent reduction in the incisional nociceptive hyperalgesia was exhibited by eriocitrin, with a marked antinociception observed at doses of 15 mg/kg (P<0.05 during 30-60 minutes) and 30 mg/kg (P<0.05, P<0.01 during 30-120 minutes). The antinociceptive effect of eriocitrin (30 mg/kg) was strongly blocked by the antagonists of the opioid receptor, naltrexone, and GABAA receptor, bicuculline, thereby suggesting the involvement of opioidergic and GABAergic mechanisms in the nociception, reducing proclivity of eriocitrin during transmission of incisional nociception. These results concluded that eriocitrin has a potent antinociceptive effect in postoperative pain conditions, probably mediated through opioid and GABAA receptors.


Crystal structures of Streptomyces tsukubaensis sigma factor SigG1 and anti-sigma RsfG.
Transcription of specific genes in bacteria under environmental stress is frequently initiated by extracytoplasmic function (ECF) σ factors. ECFs σ factors harbour two conserved domains, σ2 and σ4, for transcription initiation by recognition of the promoter region and recruitment of RNA polymerase (RNAP). The crystal structure of Streptomyces tsukubaensis SigG1, an ECF56-family σ factor, was determined revealing σ2, σ4 and the additional carboxi-terminal domain SnoaL_2 tightly packed in a compact conformation. The structure of anti-sigma RsfG was also determined by X-ray crystallography and shows a rare β-barrel fold. Analysis of the metal binding motifs inside the protein barrel are consistent with Fe(III) binding, which is in agreement with previous findings that the Streptomyces tsukubaensis ECF56 SigG1-RsfG system is involved in metal-ion homeostasis.


Trafficking Ion Transporters to the Apical Membrane of Polarized Intestinal Enterocytes.
Epithelial cells lining the gastrointestinal tract require distinct apical and basolateral domains to function properly. Trafficking and insertion of enzymes and transporters into the apical brush border of intestinal epithelial cells is essential for effective digestion and absorption of nutrients. Specific critical ion transporters are delivered to the apical brush border to facilitate fluid and electrolyte uptake. Maintenance of these apical transporters requires both targeted delivery and regulated membrane recycling. Examination of altered apical trafficking in patients with Microvillus Inclusion disease caused by inactivating mutations in MYO5B has led to insights into the regulation of apical trafficking by elements of the apical recycling system. Modeling of MYO5B loss in cell culture and animal models has led to recognition of Rab11a and Rab8a as critical regulators of apical brush border function. All of these studies show the importance of apical membrane trafficking dynamics in maintenance of polarized epithelial cell function.


[Thrombophilia as a risk factor for central retinal vein occlusion].
Central retinal vein occlusion is associated with systemic conditions, such as arterial hypertension, diabetes, hypercholesterolemia, but also with certain hypercoagulability states (thrombophilia). Growing evidence indicates, that the presence of antiphospholipid antibodies and elevated plasma homocysteine levels predispose to central retinal vein occlusion. In younger patients, factor V Leiden (Arg506Gln) could increase the risk of this disease. Other probable causes of thrombophilia related to retinal vein occlusion include increased levels of plasminogen activator inhibitor 1 and lipoprotein (a), which impair fibrinolysis.


Dynamically weighted multiconfiguration self-consistent field: multistate calculations for F+H2O-->HF+OH reaction paths.
A novel method of dynamically adjusted weighting factors in state-averaged multiconfiguration self-consistent-field calculations (SA-MCSCF) is described that is applicable to systems of arbitrary dimensionality. The proposed dynamically weighted approach automatically weights the relevant electronic states in each region of the potential energy surface, smoothly adjusting between these regions with an energy dependent functional. This method is tested on the F(2P)+H2O-->HF+OH(2Pi) reaction, which otherwise proves challenging to describe with traditional SA-MCSCF methods due to (i) different asymptotic degeneracies of reactant (threefold) and product (twofold) channels, and (ii) presence of low-lying charge transfer configurations near the transition state region. The smoothly varying wave functions obtained by dynamically weighted multiconfigurational self-consistent field represent excellent reference states for high-level multireference configuration interaction calculations and offer an ideal starting point for construction of multiple state potential energy surfaces.


Exercise induced ventricular gradient in a young patient with a positive treadmill test and normal coronary arteries.
Exercise induced intraventricular gradients have been reported during exercise stress echocardiogram in a few cases. We describe a clinical case of a 23-year old-male with a positive treadmill exercise test and normal coronary angiogram given an exercise stress echocardiogram who developed a significant intraventricular gradient. We discuss the possible physiopathologic explanation for this event.


Characterization of Fungi Associated With Wood Decay of Tree Species and Grapevine in Greece.
A two-year survey was conducted to identify fungi associated with wood decay in a range of tree species and grapevine. Fifty-eight fungal strains isolated from plants of 18 species showing typical wood decay symptoms were characterized by morphological, physiological, and molecular analyses. By 5.8S rRNA gene-ITS sequencing analysis, these isolates were classified into 25 distinct operational taxonomic units, including important phytopathogenic species of the phyla Pezizomycotina and Agaricomycotina, such as Fomitiporia, Inonotus, Phellinus, Inocutis, Fuscoporia, Trametes, Fusarium, Eutypa, Phaeomoniella, Phaeoacremonium, and Pleurostomophora spp. The white rot basidiomycetes Fomitiporia mediterranea (20 isolates, 34.5%) and Inonotus hispidus (6 isolates, 10.3%) were the most prevalent. Pathogenicity tests revealed for the first time that certain fungal species of the genera Fomitiporia, Inonotus, Phellinus, Pleurostomophora, and Fusarium caused wood infection of various tree species in Greece and worldwide. To the best of our knowledge, this is the first report of F. mediterranea as the causal agent of wood decay in pear, pomegranate, kumquat, and silk tree. This is also the first record of Inonotus hispidus, Phellinus pomaceus, Pleurostomophora richardsiae, and Fusarium solani in apple, almond, avocado, and mulberry tree, respectively, whereas P. richardsiae was associated with wood infection of olive tree for the first time in Greece. Cross pathogenicity tests with F. mediterranea strains originated from grapevine applied on other woody hosts and from olive on grapevine demonstrated partial host specificity of the fungus. The potential of F. mediterranea to transinfect hosts other than those originated, along with the host range extension of the fungus, is discussed.


Sandflies and leishmaniasis in Germany.
This study has provided evidence for the natural occurrence of sandflies in Germany. Two species belonging to the genus Phlebotomus were detected. Phlebotomus (Larroussius) perniciosus, a proven vector of leishmaniasis, was found in association with an autochthonous case of canine leishmaniasis near Kaiserslautern. Two hundred thirty-seven specimens of Phlebotomus (Transphlebotomus) mascittii were caught in 17 different locations in Baden-Wuerttemberg and Rhineland-Palatinate. The northernmost finding in Germany (and Europe) was near Cochem (Moselle). P. mascittii has not yet been confirmed as a vector of leishmaniasis, but its competence is strongly suspected. In addition to the detection of the vector, since 1991, there have been 11 cases of leishmaniasis in Germany in which an autochthonous origin was confirmed or which were highly likely to have been of indigenous origin. Data from the German meteorological service indicate that Germany currently has a Mediterranean climate, with an annual average temperature of 10 degrees C being reached or exceeded in several regions. This type of climate is also appropriate for the living conditions of sandflies. Therefore, it is assumed that sandflies have a greater geographical distribution in Germany than the first studies suggested, being mainly restricted to the southern region of Baden-Wuerttemberg. The risk of an autochthonous canine infection occurring in Germany is very low. The rapidly increasing number of imported cases of leishmaniasis in dogs means that special attention must be focused on veterinary advice to dog owners about prophylaxis. The results indicate that the use of repellents and preventive behavioural measures is vital.


Nature and chlorine reactivity of organic constituents from reclaimed water in groundwater, Los Angeles County, California.
The nature and chlorine reactivity of organic constituents in reclaimed water (tertiary-treated municipal wastewater) before, during, and after recharge into groundwater at the Montebello Forebay in Los Angeles County, CA, was the focus of this study. Dissolved organic matter (DOM) in reclaimed water from this site is primarily a mixture of aromatic sulfonates from anionic surfactant degradation, N-acetyl amino sugars and proteins from bacterial activity, and natural fulvic acid, whereas DOM from native groundwaters in the aquifer to which reclaimed water was recharged consists of natural fulvic acids. The hydrophilic neutral N-acetyl amino sugars that constitute 40% of the DOM in reclaimed water are removed during the first 3 m of vertical infiltration in the recharge basin. Groundwater age dating with 3H and 3He isotopes, and determinations of organic and inorganic C isotopes, enabled clear differentiation of recent recharged water from older native groundwater. Phenol structures in natural fulvic acids in DOM isolated from groundwater produced significant trihalomethanes (THM) and total organic halogen (TOX) yields upon chlorination, and these structures also were responsible for the enhanced SUVA and specific fluorescence characteristics relative to DOM in reclaimed water. Aromatic sulfonates and fulvic acids in reclaimed water DOM produced minimal THM and TOX yields.


Real-time and three-dimensional MRI for diagnosis of pharyngoceles.
In the evaluation of patients with local pathologic dilatation inside the upper airway a pressure-related testing seems important for understanding its pathophysiology and for developing a concept of intra-individually adjusted therapy. Commonly used diagnostic techniques like endoscopy or medical imaging including ultrasound, barium swallow or computer-assisted tomography (CT) have shown limitations either in evaluating a dynamic process or assessing the entirety of cervical structures. This article presents a case report of a professional trumpet player with bilateral pharyngoceles, introducing real-time and three-dimensional (3D) MRI as a helpful tool in the diagnosis of pressure dependent pathologies in the upper airway. With the use of MRI the complete sub- and supraglottic airway can be viewed simultaneously, avoiding the distortion which can occur with endoscopy. Thus, it was possible to evaluate the pharyngoceles pressure-related pathophysiology, from which a successful therapy could be conceived which included modifying the musician's blowing technique.


Delayed self-synchronization in homoclinic chaos.
The chaotic spike train of a homoclinic dynamical system is self-synchronized by applying a time-delayed correction proportional to the laser output intensity. Due to the sensitive nature of the homoclinic chaos to external perturbations, stabilization of very long-periodic orbits is possible. On these orbits, the dynamics appears chaotic over a finite time, but then it repeats with a recurrence time that is slightly longer than the delay time. The effect, called delayed self-synchronization, displays analogies with neurodynamic events that occur in the buildup of long-term memories.


MOTION PICTURE STUDY OF THE TOXIC ACTION OF STREPTOLYSINS ON LEUCOCYTES.
The initial morphologic alteration in rabbit polymorphonuclear leucocytes exposed to streptolysin is rapid and extensive lysis of cytoplasmic granules. The granules appear to rupture directly into the cell sap. Within a few minutes following degranulation, the leucocyte rounds up, filamentous processes appear on the cell membrane, the cytoplasm liquefies, and finally the nuclear lobes swell and fuse. Streptolysin O causes these changes in intact leucocytes when added in concentrations only slightly higher than those required for release of hydrolases from isolated liver lysosomes, and furthermore exerts its action on granulocytes promptly. On the other hand streptolysin S acts on white cells only after a 15 to 30 minute delay, and the levels necessary to disrupt granules in leucocytes are considerably higher than those which act on lysosome suspensions. Exposure of rabbit alveolar macrophages to streptolysin O also results in lysis of granules, soon followed by alterations in the cytoplasm and membrane. The observations are in accord with the hypothesis that streptolysins penetrate the leucocyte membrane and bring about lysis of granules. Autolytic enzymes released from the granules might then be responsible for the subsequent damage seen in various other cell structures.


Preparation of photocontrollable, nontoxicity complex of phenylazophenylalanine modified CdS quantum dots with cyclodextrin.
A novel complex of beta-cyclodextrin with phenylazophenylalanine (PAP)-conjugated CdS quantum dot (Fazo-CdS QD) was fabricated for a photocontrollable toxicity study of CdS. Photocontrolling release of Fazo-CdS QDs from the complex was confirmed under UV irradiation by the steady state photoluminescence (PL) spectroscopy. The cytotoxicity of the surface modified CdS QDs was evaluated in vivo. The results suggest that the Fazo-CdS QDs conjugated with beta-CD could be almost nontoxicity, which may have great potential applications in biological labeling and imaging.