Fracture toughness improvements of dental ceramic through use of yttria-stabilized zirconia (YSZ) thin-film coatings.
The aim of this study was to evaluate strengthening mechanisms of yttria-stabilized zirconia (YSZ) thin film coatings as a viable method for improving fracture toughness of all-ceramic dental restorations. Bars (2mm×2mm×15mm, n=12) were cut from porcelain (ProCAD, Ivoclar-Vivadent) blocks and wet-polished through 1200-grit using SiC abrasive. A Vickers indenter was used to induce flaws with controlled size and geometry. Depositions were performed via radio frequency magnetron sputtering (5mT, 25°C, 30:1 Ar/O2 gas ratio) with varying powers of substrate bias. Film and flaw properties were characterized by optical microscopy, scanning electron microscopy (SEM), and X-ray diffraction (XRD). Flexural strength was determined by three-point bending. Fracture toughness values were calculated from flaw size and fracture strength. Data show improvements in fracture strength of up to 57% over unmodified specimens. XRD analysis shows that films deposited with higher substrate bias displayed a high %monoclinic volume fraction (19%) compared to non-biased deposited films (87%), and resulted in increased film stresses and modified YSZ microstructures. SEM analysis shows critical flaw sizes of 67±1μm leading to fracture toughness improvements of 55% over unmodified specimens. Data support surface modification of dental ceramics with YSZ thin film coatings to improve fracture toughness. Increase in construct strength was attributed to increase in compressive film stresses and modified YSZ thin film microstructures. It is believed that this surface modification may lead to significant improvements and overall reliability of all-ceramic dental restorations.


[A novel method for extracting leaf-level solar-induced fluorescence of typical crops under Cu stress].
The leaf-level solar-induced fluorescence changes when the typical crops are under Cu stress, which can be considered as a sensitive indicator to estimate the stress level. In the present study, wheat (Triticum aestivum L.), pea (Pisum sativum L.) and Chinese cabbage (Brassica campestris L.) were selected and cultured with copper solutions or copper polluted soil with different Cu stress. The apparent reflectance of leaves was measured by an ASD Fieldspec spectrometer and an integrating sphere. As the apparent reflectance was seldom affected by the fluorescence emission at 580-650 and 800-1000 nm, so the apparent solar-induced fluorescence can be separated from the apparent reflectance based on PROSPECT model. The re-absorption effect of chlorophyll was corrected by three methods, called GM (Gitelson et al.'s model), AM (Agati et al.'s model) and LM (Lagorio et al.'s model). After the re-absorption correction, the solar-induced fluorescence under different Cu stress was obtained, and a positive relationship was found between the height of far RED fluorescence (FRF) and the copper contents in leaves.


[Structural features of cardiomyocytes in the atrialized right ventricle in patients with Ebstein anomaly].
Intraoperative biopsy specimens were used to analyze the sizes and ultrastructure of cardiomyocytes (CMC) in the atrialized right ventricle (ARV) versus those in the right ventricle (RV) and right atrium (RA) in 32 patients aged 9 months to 57 years with Ebstein anomaly. The mean CMC diameter in ARV, RV, and RA did not differ significantly in patients less than 10 years; that was equal in ARV and RV, but higher in RA in patients over 10 years of age. No specific atrial granules were found in the CMC of ARV, RV, and RA; but T system channels and multiple intercalated disks were encountered significantly more frequently than in the RA cells. Individual CMCs showed abnormal myofibrils with specific accumulations of Z-band material (more commonly in RA), as well as nuclear displacement under the sarcolemma (more commonly in ARV and RV). Conclusion. ARV cardiomyocytes preserve ventricular specificity in patients with Ebstein anomaly.


The concept of readiness to change.
Readiness is associated with change, yet there is little understanding of this construct. The purpose of this study was to examine readiness; its referents, associated factors and the resulting consequences. In the course of nursing five clients living with multiple sclerosis over a 7-month period using a Reflective Practice Model, data were systematically gathered using open-ended and then more focused questioning. Data collected during 42 client encounters (28 face-to-face encounters; 14 telephone contacts) were analysed using Chinn and Kramer's concept analysis technique. Findings. The concept of readiness was inductively derived. Readiness is both a state and a process. Before clients can create change they need to become ready to change. A number of factors trigger readiness. These include when: (a) clients perceive that a health concern is not going to resolve, (b) a change in a client's physical condition takes on new significance, (c) clients feel better able to manage their stress, (d) clients have sufficient energy, (e) clients perceive that they have adequate support in undertaking change. When one or more of these factors is present clients become ready to consider change. The process of readiness involves recognizing the need to change, weighing the costs and benefits and, when benefits outweigh costs, planning for change. The desire to change and to take action determines clients' degree of readiness. When they experience a high degree of readiness they report less anger, less depression, and view their condition in a more positive light. In contrast, when they experience a low degree of readiness they report feeling depressed, afraid and vulnerable in the face of change. Nursing has an important role to play in creating conditions to support change. To fulfil this role, nurses need to be able to assess readiness for change and the factors that enable it and then to intervene in ways that facilitate readiness.


Tick-borne encephalitis and Lyme borreliosis: comparison of habitat risk assessments using satellite data (an experience from the Central Bohemian region of the Czech Republic).
The vegetation types have been used as the indicators of an ecosystem suitable for high incidence of Ixodes ricinus ticks and their hosts, for the circulation of tick-borne diseases pathogens and, accordingly, for the existence of natural foci of these infections, namely tick-borne encephalitis (TBE) and Lyme borreliosis (LB). The method of remote sensing offers a suitable solution to this problem. We attempted to prepare the habitat risk assessment maps on the territory (11,500 km2) of Central Bohemia (Czech Republic) using Landsat 5 TM imagery. Nine forest classes have been recognized in the satellite data and further identified in a field checking botanical survey. Beside the conclusions dealing with the importance of different plant types for I. ricinus occurrence, also the epidemiological TBE and LB maps based on human cases contracted in the territory under study were exploited for the evaluation of particular forest classes significance, and for the comparison of results achieved. Apart from a general pattern of risk gradation from coniferous to deciduous wood types, both TBE and LB data suggest a specific position of the heterogeneous deciduous wood class (including mainly young deciduous stands and stand ecotones with highly heterogeneous structure). Epidemiological significance of the other particular forest classes was assessed by the degrees of positive class-to-risk associations (see Table 1 and 2).


The 3, 4-didehydroretinal chromophore of goldfish porphyropsin.
The isomeric configuration of the 3,4-didehydroretinal chromophore of goldfish porphyropsin was determined by high performance liquid chromatography (HPLC) and by the regeneration of this visual pigment with authentic isomers of 3,4-didehydroretinal. A nonisomerizing, quantitative method using hydroxylamine and methylene chloride was employed to extract the 3,4-didehyroretinal chromophore from the rod outer segment membrane (containing the porphyropsin). When this extracted chromophore was injected into the HPLC, only a single major peak was observed and this peak coeluted with the authentic 11-cis 3,4-didehydroretinyl oxime. This suggests that the chromophore of goldfish porphyropsin is 11-cis 3,4-didehydroretinal. When the bleached rod outer segments (containing the opsin) were incubated with different 3,4-didehydroretinal isomers (13-cis, 11-cis, 9-cis, and all-trans), only the 11-cis isomer resulted in the degeneration of porphyropsin. This also suggests that the porphyropsin chromophore exists in the 11-cis configuration.


Disentangling affect from self-esteem using subliminal conditioning.
Across three experiments, participants underwent conditioning sequences where the self-referential term I AM (Conditioned Stimulus, or CS+) or a scrambled counterpart M IA (CS-) was paired with either neutral (Unconditioned Stimulus, or US-) or positive attributes (US+). CS and US were presented under subliminal and/or visible conditions. A normalized indicator of affective shift and an explicit self-esteem measure were deployed as outcome measures. In Experiment 1 (N = 60), subliminal CS+ followed by visible US+ produced a significant affective shift only. Experiment 2 (N = 59) presented CS and US under subliminal conditions, which did not influence either outcome measure. In Experiment 3 (N = 60), visible CS appeared with visible US, which resulted in a significant effect on explicit self-esteem only. These findings highlight the central roles of CS and/or US visibility towards influencing reported affect and self-esteem. We theorize that configural components of subliminally presented stimuli can become perceptually encoded and influence self-related affect non-consciously.


MUC2 gene suppression in human colorectal carcinomas and their metastases: in vitro evidence of the modulatory role of DNA methylation.
The development of the majority of colorectal carcinomas is associated with a diminished expression of the intestinal mucin MUC2 in the tumor cells. The significance and the mechanism of this alteration are not yet known. We sought to determine the molecular basis of this tumor-associated change and to investigate the extent to which it might also relate to metastases. MUC2 gene expression was compared in normal (N), carcinomatous (T), and metastatic tissues (M) from nine patients by immunohistochemistry, in situ hybridization, and Northern blotting. Immunohistochemistry and in situ hybridization showed consistently lower amounts of the expressed protein and mRNA in T and in M than in N; quantitative analysis by Northern blotting confirmed that the differences between MUC2 mRNA expression between N, T, and M were significant, the expression in metastases being less than 5% of that in the normal colonic tissue. The influence of DNA methylation as a possible regulatory mechanism of MUC2 gene expression was tested after the 5' and 3'-regions flanking the first exon of MUC2 were recovered from a genomic DNA library and used as probes in Southern blot. The DNA was isolated from colon carcinoma cell lines expressing MUC2 strongly (LS174T) or moderately (T84) and from that which was nonexpressing (Colo 205), and it was digested with the methylation-sensitive enzyme HpaII. The Southern blot patterns indicated that the increased methylation in the promoter region was concomitant with the decrease of MUC2 mRNA expression. Methylation of the promoter region ligated into a reporter vector suppressed the expression of the luciferase reporter gene in the three investigated cell lines. Furthermore, the expression of MUC2 gene was enhanced by treating the MUC2-expressing colon carcinoma cells with 5-aza-2'-deoxycytidine, a methylation-inhibiting agent. To our knowledge this is the first report to show that: (a) MUC2 gene is strongly suppressed in liver and lymph node metastases of colorectal carcinomas, and (b) suppression of MUC2 gene in colon carcinoma cells in vitro is associated with methylation of the promoter region.


Generality of the prerequisite of conidium attachment to a hydrophobic substratum as a signal for germination among Phyllosticta species.
It has been shown that conidia of Phyllosticta ampelicida require attachment to a substratum to initiate germination. Furthermore this attachment occurs only on hydrophobic surfaces. This study was initiated to ascertain the breadth of this phenomenon among other species of the genus Phyllosticta. We tested 23 isolates of Phyllosticta representing at least 14 named species. These isolates were collected from North America, Asia and Africa. For 22 of the 23 isolates tested spore attachment occurred at a rate of 60-100% on hydrophobic polystyrene but at 0-5% on hydrophilic polystyrene. The one exception to the preference for a hydrophobic substratum for attachment was an unnamed species of Phyllosticta from Rhus glauca that attached less than 10% on either surface. A similar response was observed when assaying germination and appressorium formation for 17 isolates. Germination and appressorium formation for these isolates proceeded on hydrophobic polystyrene but not on nutrient agar, which is hydrophilic. In five of the tested isolates germination was high on both hydrophobic polystyrene and hydrophilic nutrient media. The isolate from Rhus glauca did not germinate appreciably on either surface. Taken together these results suggest that the requirement for conidium contact/attachment to trigger germination is pervasive to the genus Phyllosticta.


Negative emotion-driven impulsivity predicts substance dependence problems.
Impulsivity is predominant among users of several drugs of abuse including alcohol, cocaine, and amphetamines, and it is considered a risk factor for later development of alcohol and substance abuse and dependence. However, there is little consensus on how impulsivity should be defined and measured, and there are few studies on the relationship between separate dimensions of impulsivity and substance dependence. We used a multidimensional measure of impulsivity (the UPPS scale) to examine differences between 36 individuals with substance dependence (ISD) and 36 drug-free controls on the dimensions of urgency, lack of premeditation, lack of perseverance, and sensation seeking. In addition, we examined which dimensions of impulsivity better predicted addiction-related problems as measured with the addiction severity index. Results revealed that ISD show high scores on dimensions of urgency, lack of perseverance, and lack of premeditation (effect sizes ranging from 1.10 to 1.96), but not on sensation seeking. Among the different impulsivity dimensions, urgency was the best predictor of severity of medical, employment, alcohol, drug, family/social, legal and psychiatric problems in ISD, explaining 13-48% of the total variance of these indices. Furthermore, urgency scores alone correctly classified 83% of the participants in the ISD group. Urgency is characterized by a tendency to act impulsively in response to negative emotional states. Thus, our results could have important implications for novel treatment approaches for substance dependence focused on emotional regulation.


Estrogen in autoimmunity: expression of estrogen receptors in thymic and autoimmune T cells.
To identify the targets of estrogen in immune system lymphocytes and to examine gender differences in autoimmunity. RNA samples from purified lymphocyte subsets were analyzed for the presence of mRNA for estrogen receptor alpha and beta (ER alpha and ER beta). Groups of male, female, and testicular-feminized mice were compared for autoantibody production. Autoimmune-prone lpr (Fas-deficient), testicular-feminized (Tfm, androgen receptor-deficient) and wild-type mice were studied. Lymphocyte subsets were purified by fluorescence-activated cell sorting (FACS) and RNA was assessed for the presence of estrogen receptor sequences using specific oligonucleotide primers and the reverse transcription-polymerase chain reaction (RT-PCR). Spontaneous and induced antibody production in mice was determined by enzyme-linked immunosorbent assay (ELISA). ER alpha was expressed in all lymphocyte subsets examined. ER beta was expressed at low levels in thymic CD4/CD8- T cells in wild-type mice and at high levels in the peripheral CD4-/CD8- T cells in lpr mice. Both spontaneous and induced autoantibody production was higher in female lpr mice than in male lpr mice. The presence of ERs in lymphocytes indicates that estrogen may affect immune cells during their development and mature function. The selective expression of ER beta may help explain some of the physiological effects of estrogen and its pharmacologic analogues and may lead to means to direct estrogen analogues to such cells. Such effects may be explored in lpr mice, given the enhanced capacity of female lpr mice for autoantibody production.


Reviewing the preclinical curriculum in a Problem Based Learning driven medical program: challenges and strategies.
This article was migrated. The article was marked as recommended. In order for medical curricula to remain progressive and contemporary, continuous review is critical to ensure that the learners are directed to achieve the intended goals and become workforce ready. We developed a framework for continuous curriculum review at the School of Medicine Fremantle (The University of Notre Dame Australia), taking the key aspects of a curriculum review process into consideration. In planning and implementing the review process we identified several challenges, including management of metadata, work load on staff members, and evaluation. These challenges were addressed successfully by applying necessary strategies using limited resources. The framework we have developed provides a guide to key stakeholders who are involved in medical curriculum review and development.


Absence of Neuropathology With Prolonged Isoflurane Sedation in Healthy Adult Rats.
The use of isoflurane sedation for prolonged periods in the critical care environment is increasing. However, isoflurane-mediated neurotoxicity has been widely reported. The goal of the present study was to determine whether long-term exposure to low-dose isoflurane in mechanically ventilated rodents is associated with evidence of neurodegeneration or neuroinflammation. Adult female Sprague-Dawley rats were used in this study. Experimental animals (n=11) were induced with 1.5% isoflurane, intubated, and given a neuromuscular blockade with α-cobratoxin. EEG electrodes were surgically implanted, subcutaneous precordial EKG Ag wire electrodes, and bladder, femoral artery, and femoral vein cannulas permanently placed. After these procedures, the isoflurane concentration was reduced to 0.5% and, in conjunction with the neuromuscular blockade, continued for 7 days. Arterial blood gases and chemistry were measured at 3 time points and core body temperature servoregulated and maintenance IV fluids were given during the 7 days. Experimental animals and untreated controls (n=9) were euthanized on day 7. Immunohistochemical and cytochemical assays did not detect evidence of microgliosis, astrocytosis, neuronal apoptosis or necrosis, amyloidosis, or phosphorylated-tau accumulation. Blood glucose levels were significantly reduced on days 3/4 and 6/7 and partial pressure of oxygen was significantly reduced, but still within the normal range, on day 6/7. All other blood measurements were unchanged. No neuropathologic changes consistent with neurotoxicity were detected in the brain after 1 week of continuous exposure to 0.5% isoflurane in healthy rats. These data suggest that even long exposures to low concentrations of isoflurane have no overt consequences on neuropathology.


Cyclophosphamide diminishes inflammation and prolongs transgene expression following delivery of adenoviral vectors to mouse liver and lung.
Immune responses to adenovirus-mediated gene transfer contribute to the problems of transient recombinant gene expression, inflammation, and difficulties with vector readministration. Activation of CD4+ T cells is required for full realization of effector function of both CD8+ T cells (i.e., cytotoxic T cells) and B cells (i.e., neutralizing antibody). We evaluate in this study the effectiveness of a short course of high-dose cyclophosphamide to block immune responses in mice administered vector into lung and liver of C57BL/6 mice. Administration of cyclophosphamide with vector directed to liver blocked activation and mobilization of both CD4+ and CD8+ T cells. As a result, transgene expression was prolonged, inflammation was reduced, and, at the higher doses of cyclophosphamide, formation of neutralizing antibody was prevented and the vector was successfully readministered. Similar studies in the lung demonstrated an effective blockade of T and B cell responses. In contrast to the liver, where it was easier to stabilize transgene expression than to prevent neutralizing antibody, cyclophosphamide prevented the formation of neutralizing antibodies at all doses in the lung, whereas stabilization of transgene expression was only achieved at the highest dose. These experiments begin to define the parameters by which cyclophosphamide could be used as an adjunct in gene therapy.


Altered expression of gustatory-signaling elements in gastric tissue of morbidly obese patients.
Sensing of nutrients in the stomach is of crucial importance for the regulation of ingestive behavior especially in the context of metabolic dysfunctions such as obesity. Cells in the gastric mucosa with taste-signaling elements are considered as candidates for sensing the composition of ingested food and consequently modulate gastrointestinal processes. To assess whether obesity might have an impact on gastric chemosensory cells, gastric tissue samples from morbidly obese patients and normal-weight subjects were compared using a reverse transcriptase (RT)-PCR, qPCR and immunohistochemical approach. Analysis of biopsy tissue samples from human stomach revealed that transcripts for the taste-signaling elements, including the receptor T1R3 involved in the reception of amino acids and carbohydrates, the fatty acid receptor GPR120, the G protein gustducin, the effector enzyme PLCβ2 and the ion channel TRPM5 are present in the human gastric mucosa and led to the visualization of candidate chemosensory cells in the stomach expressing gustatory marker molecules. RT-PCR and qPCR analyses indicated striking differences in the expression profiles of specimens from obese subjects compared with controls. For GPR120, gustducin, PLCβ2 and TRPM5 the expression levels were increased, whereas for T1R3 the level decreased. Using TRPM5 as an example, we found that the higher expression level was associated with a higher number of TRPM5 cells in gastric tissue samples from obese patients. This remarkable change was accompanied by an increased number of ghrelin-positive cells. Our findings argue for a relationship between the amount of food intake and/or the energy status and the number of candidate chemosensory cells in the gastric mucosa.


[Study on chemical constituents of Citrullus vulgaris Schrad vine (II)].
To study the chemical constituents of ethyl acetate fraction of Citrullus vulgaris Schrad vine. Compounds were isolated and purified by polyamide column chromatography, silica gel column chromatography, thin layer chromatography and sephadex gel column chromatography. Their structures were elucidated on the basis of physicochemical properties and spectral data. Ten compounds were isolated from Citrullus vulgaris Schrad vine and elucidated as: pentadecanoic acid (1), monopentadecanoin (2), 2, 3-dihydroxypropyl nonadecoate (3), lignoceric acid-2, 3-dihydroxy-propanenyl ester (4), lancerebroside 5 (5), salicylic acid (6), 4-hydroxybenzoic acid (7), hydroquinone (8), succinic acid (9) and vanillic acid (10). Compounds 1 - 10 are obtained from Citrullus vulgaris Schrad vine for the first time.


(4S)-4-(3-18F-fluoropropyl)-L-glutamate for imaging of xC transporter activity in hepatocellular carcinoma using PET: preclinical and exploratory clinical studies.
(4S)-4-(3-(18)F-fluoropropyl)-l-glutamate ((18)F-FSPG, or BAY 94-9392) is a new tracer to assess system x(C)(¯) transporter activity with PET. The aim of this study was to explore the tumor detection rate of (18)F-FSPG, compared with that of (18)F-FDG, in patients with hepatocellular carcinoma (HCC). Preclinically, in vivo HCC models of orthotopically implanted Huh7 and MH3924a cancer cells were studied with (18)F-FSPG in Naval Medical Research Institute nude mice (n = 3) and August-Copenhagen Irish rats (n = 4), respectively. Clinically, 5 patients with HCC who had hyper- or isometabolic lesions on (18)F-FDG PET were enrolled for evaluation of the tracer. Dynamic whole-body PET images with (18)F-FSPG were acquired for up to 120 min after injection of approximately 300 MBq of (18)F-FSPG. Immunohistochemical expression levels of the xCT subunit of the system x(C)(¯) and CD44 of HCC were studied in 4 patients with HCC. Strong tumor uptake and low background from nontarget tissue allowed excellent tumor visualization in animal models with orthotopically implanted liver tumors. (18)F-FSPG PET procedures were well tolerated in all patients. (18)F-FSPG PET and (18)F-FDG detected lesions in 5 of 5 and 3 of 5 patients, respectively. The maximal standardized uptake values (SUV) were comparable ((18)F-FSPG, 4.7 ± 3.2; (18)F-FDG, 6.1 ± 2.9). The ratios of maximal SUV of the tumor to mean SUV of normal liver were also comparable ((18)F-FSPG, 3.6 ± 2.2; (18)F-FDG, 2.7 ± 1.3), but the mean SUV of normal liver of (18)F-FSPG was significantly lower than that of (18)F-FDG (P < 0.05). Two patients with HCC who showed both xCT and CD44 expression had moderate or intense accumulation of (18)F-FSPG, but the remaining 2 patients with negative CD44 expression showed mild uptake. (18)F-FSPG was successfully translated from preclinical evaluation into patients with HCC. (18)F-FSPG may be a promising tumor PET agent with a high cancer detection rate in patients with HCC.


Relationship of personal, situational, and environmental factors to injury experience in commercial fishing.
Commercial fishing work involves a variety of activities and is hazardous. While much is understood to mitigate fatalities in this industry, research must further explore nonfatal injury characteristics, factors related to injury, and potential injury prevention strategies. This paper determines if fishing experience is associated with injury risk and explores common work activities associated with injury. Key informant interviews and a survey of fishermen were conducted to refine work activity codes and collect injury experiences. Independent sample t-tests compared the means of the years fishing by injury incident for all crab fishermen then stratified by position. Descriptive statistics explored the nature of injury in relation to work activity. The level of experience was significantly lower for injured fishermen compared to fishermen who reported no injuries, but when stratified by position at the time of the injury, the association of injury to experience was only significant for owners. This stratified result demonstrates that the work activity, rather than experience, drives the apparent relationship of experience to injury. Being tired (24%) and weather (26%) were indicated as contributing factors at the time of injury. Modifying the work environment to better control hazards would benefit all fishermen, regardless of their experience, age, or position. Further work into effective interventions that fishermen would adopt is needed to reduce injury risk. Any formal or informal training of new fishermen should focus on the most hazardous activities, but more experienced fishermen would also benefit. Additionally, effective training or interventions for fatigue management, and decision support tools for weather- and navigation-related decisions would further reduce risk of at sea injuries. Injury prevention training, for all fishermen, regardless of their position and years of experience, should cover the most hazardous tasks, fatigue risk management strategies, and weather decisions.


Computational Identification of Metabolic Pathways of Plasmodium falciparum using the k-Shortest Path Algorithm.
Plasmodium falciparum, a malaria pathogen, has shown substantial resistance to treatment coupled with poor response to some vaccines thereby requiring urgent, holistic, and broad approach to prevent this endemic disease. Understanding the biology of the malaria parasite has been identified as a vital approach to overcome the threat of malaria. This study is aimed at identifying essential proteins unique to malaria parasites using a reconstructed iPfa genome-scale metabolic model (GEM) of the 3D7 strain of Plasmodium falciparum by filling gaps in the model with nineteen (19) metabolites and twenty-three (23) reactions obtained from the MetaCyc database. Twenty (20) currency metabolites were removed from the network because they have been identified to produce shortcuts that are biologically infeasible. The resulting modified iPfa GEM was a model using the k-shortest path algorithm to identify possible alternative metabolic pathways in glycolysis and pentose phosphate pathways of Plasmodium falciparum. Heuristic function was introduced for the optimal performance of the algorithm. To validate the prediction, the essentiality of the reactions in the reconstructed network was evaluated using betweenness centrality measure, which was applied to every reaction within the pathways considered in this study. Thirty-two (32) essential reactions were predicted among which our method validated fourteen (14) enzymes already predicted in the literature. The enzymatic proteins that catalyze these essential reactions were checked for homology with the host genome, and two (2) showed insignificant similarity, making them possible drug targets. In conclusion, the application of the intelligent search technique to the metabolic network of P. falciparum predicts potential biologically relevant alternative pathways using graph theory-based approach.


Prostaglandin hydroperoxidase-catalyzed activation of certain N-substituted aryl renal and bladder carcinogens.
Certain carcinogens are thought to induce renal and bladder cancer following metabolic activation. We propose a model system for this activation and provide supporting experimental evidence. This model proposes that renal and bladder carcinogens' entry into the urinary tract is facilitated, that carcinogens are activated by the prostaglandin hydroperoxidase activity of prostaglandin endoperoxide synthetase (PES), and that activation results in covalent binding to nucleic acids which can initiate carcinogenesis. Benzidine and the 5-nitrofuran HMN were shown to inhibit uptake of organic anions and cations, respectively. Carcinogen binding to DNA was dependent upon specific unsaturated fatty acid substrates and prevented by specific inhibitors of PES, i.e., aspirin. Activation with organic peroxides or H(2)O(2) was inhibited by antioxidants but not aspirin. Horseradish peroxidase (HRP) metabolized benzidine but not ANFT. Acetaminophen and the 5-nitrofurans ANFT and HMN prevented PES (14)C-benzidine metabolism. However, only acetaminophen inhibited HRP metabolism of benzidine. The only aerobic metabolism we have observed of 5-nitrofurans is PES-catalyzed. Aspirin (0.5% in the diet) inhibited rat bladder hyperplastic lesions induced by feeding 0.1% or 0.2% FANFT for 6 or 12 weeks. Aspirin reduced bladder prostaglandin synthesis and PES metabolism of FANFT. After one year of an ongoing long-term study, gross examination reveals bladder tumors in 85% of the rats fed 0.2% FANFT and in only 37% of the rats fed FANFT plus 0.5% aspirin.


Comparative neurovirulence of selected vesicular stomatitis virus temperature-sensitive mutants of complementation groups II and III.
Weanling mice were inoculated intracerebrally with selected vesicular stomatitis virus (VSV) complementation group II and III temperature-sensitive (ts) mutants. Of the VSV ts mutants studied, only ts G32, a group III complementation mutant, appeared neurovirulent. Interestingly, neither the capacity to replicate in central nervous system tissue nor the ability to replicate in certain neurally derived continuous cell lines at semipermissive or nonpermissive temperatures appeared different among the VSV ts mutants employed. Finally, the pathological alterations in central nervous system tissue produced by VSV ts G32 were entirely different than those produced by G31 VSV ts in the group III mutant. These studies support the hypothesis that both the virological and neuropathological features produced by different VSV ts mutants are dependent upon the unique characteristics of each mutant, rather than upon a common biochemical defect shared by all members of a complementation group.


TREND-DB-a transcriptome-wide atlas of the dynamic landscape of alternative polyadenylation.
Alternative polyadenylation (APA) profoundly expands the transcriptome complexity. Perturbations of APA can disrupt biological processes, ultimately resulting in devastating disorders. A major challenge in identifying mechanisms and consequences of APA (and its perturbations) lies in the complexity of RNA 3' end processing, involving poorly conserved RNA motifs and multi-component complexes consisting of far more than 50 proteins. This is further complicated in that RNA 3' end maturation is closely linked to transcription, RNA processing and even epigenetic (histone/DNA/RNA) modifications. Here, we present TREND-DB (http://shiny.imbei.uni-mainz.de:3838/trend-db), a resource cataloging the dynamic landscape of APA after depletion of >170 proteins involved in various facets of transcriptional, co- and post-transcriptional gene regulation, epigenetic modifications and further processes. TREND-DB visualizes the dynamics of transcriptome 3' end diversification (TREND) in a highly interactive manner; it provides a global APA network map and allows interrogating genes affected by specific APA-regulators and vice versa. It also permits condition-specific functional enrichment analyses of APA-affected genes, which suggest wide biological and clinical relevance across all RNAi conditions. The implementation of the UCSC Genome Browser provides additional customizable layers of gene regulation accounting for individual transcript isoforms (e.g. epigenetics, miRNA-binding sites and RNA-binding proteins). TREND-DB thereby fosters disentangling the role of APA for various biological programs, including potential disease mechanisms, and helps identify their diagnostic and therapeutic potential.


Oxidation of β2-glycoprotein I associates with IgG antibodies to domain I in patients with antiphospholipid syndrome.
Domain I (DI) of beta-2-glycoprotein I (β2GPI) contains the immunodominant epitope for pathogenic antiphospholipid antibodies (aPL). DI is exposed in the linear form of the molecule but not in the circular form that comprises 90% of serum β2GPI. The majority of circulating β2GPI is biochemically reduced with two free thiols in Domain V. However, increased levels of oxidised β2GPI are found in patients with antiphospholipid syndrome (APS). It is not known whether oxidation of β2GPI favours the linear form of the molecule and thus promotes development of anti-DI antibodies. We investigated whether the proportion of oxidised β2GPI associates with the presence of anti-DI in APS patients. Serum samples from 44 APS patients were screened for IgG, IgM and IgA anti-DI, anti-β2GPI, anti-cardiolipin (anti-CL) and biochemically reduced β2GPI. A negative correlation was found between the proportion of β2GPI in the biochemically reduced form and IgG anti-DI levels (r = -0.54, p = 0.0002), but not with IgM or IgA anti-DI. Moreover, the proportion of β2GPI in the reduced form was lower in IgG anti-DI positive than anti-DI negative APS patients (p = 0.02). The relative amount of reduced β2GPI was no different between patients who were positive or negative for IgG, IgM and IgA anti-β2GPI or anti-CL. This study demonstrates that oxidised β2GPI lacking free cysteine-thiol groups most closely associates with IgG anti-DI positivity compared to IgG anti-CL and anti-β2GPI. Future studies are required to ascertain the directionality of this association to define causation.


Involvement of the N-terminal B-box domain of Arabidopsis BBX32 protein in interaction with soybean BBX62 protein.
Previous studies have demonstrated that Arabidopsis thaliana BBX32 (AtBBX32) represses light signaling in A. thaliana and that expression of AtBBX32 in soybean increases grain yield in multiple locations and multiyear field trials. The BBX32 protein is a member of the B-box zinc finger family from A. thaliana and contains a single conserved Zn(2+)-binding B-box domain at the N terminus. Although the B-box domain is predicted to be involved in protein-protein interactions, the mechanism of interaction is poorly understood. Here, we provide in vitro and in vivo evidence demonstrating the physical and functional interactions of AtBBX32 with another B-box protein, soybean BBX62 (GmBBX62). Deletion analysis and characterization of the purified B-box domain indicate that the N-terminal B-box region of AtBBX32 interacts with GmBBX62. Computational modeling and site-directed mutagenesis of the AtBBX32 B-box region identified specific residues as critical for mediating the interaction between AtBBX32 and GmBBX62. This study defines the plant B-box as a protein interaction domain and offers novel insight into its role in mediating specific protein-protein interactions between different plant B-box proteins.


Hepatic veno-occlusive disease: a chemotherapy-related toxicity in children with malignancies.
Hepatic veno-occlusive disease (VOD) is a major manifestation of liver toxicity associated with conventional and high-dose chemotherapy in children affected by hematologic malignancies and certain solid tumors. Clinically, patients present with jaundice, painful hepatomegaly, and fluid retention, which may evolve into multi-organ failure, a hallmark of severe disease. The pathogenesis is complex and not completely understood, but the damage to sinusoidal endothelium, typically caused by toxic metabolites released from antineoplastic drugs, is thought to play a crucial role, together with cytokine activation, immune deregulation, and coagulopathy. Diagnosis is based on clinical criteria supported by characteristic ultrasound findings, with the gold standard investigation being hepatic-venous pressure gradient measurement and biopsy. Several treatment options have been tested; the most convincing approach to date is the use of defibrotide, a novel oligonucleotide with antithrombotic and antiplatelet aggregating properties, as well as endothelial-stabilizing effects. This agent, together with other specific forms of supportive care, has shown efficacy in the treatment of established VOD and promising results in the prevention of VOD in pediatric patients receiving chemotherapy.


Realization of topological Mott insulator in a twisted bilayer graphene lattice model.
Magic-angle twisted bilayer graphene has recently become a thriving material platform realizing correlated electron phenomena taking place within its topological flat bands. Several numerical and analytical methods have been applied to understand the correlated phases therein, revealing some similarity with the quantum Hall physics. In this work, we provide a Mott-Hubbard perspective for the TBG system. Employing the large-scale density matrix renormalization group on the lattice model containing the projected Coulomb interactions only, we identify a first-order quantum phase transition between the insulating stripe phase and the quantum anomalous Hall state with the Chern number of ±1. Our results not only shed light on the mechanism of the quantum anomalous Hall state discovered at three-quarters filling, but also provide an example of the topological Mott insulator, i.e., the quantum anomalous Hall state in the strong coupling limit.


Ongoing university studies and the risk of suicide: a register-based nationwide cohort study of 5 million young and middle-aged individuals in Sweden, 1993-2011.
To investigate the risk of suicide, unnatural death and all-cause death in university students compared with non-students, taking previous educational attainment into account. Open cohort study of all residents aged 18-39 and living in Sweden at any time between 1 January 1993 and 31 December 2011. We linked data from national registers and calculated person-years during university studies for three time periods (1993-1999, 2000-2005 and 2006-2011). Time as non-student was calculated and categorised according to attained educational level. Incidence rate ratios (IRR) with 95% CIs were calculated with Poisson regression models, controlling for age and period. The cohort consisted of 5 039 419 individuals, 51% men and 49% women. Incidence of suicide (International Classification of Diseases (ICD)-9: E950-E959, ICD-10: X60-X84) or death with undetermined intent (ICD-9: E980-E989, ICD-10: Y10-Y34), unnatural death (ICD-9: E800-E999 and ICD-10: V01-Y99) and all-cause death. A total of 7316 deaths due to suicide were identified, of which 541 were registered among university students. The risk of suicide was twofold during ongoing university studies compared with when having attained university education, IRR 2.37 (95% CI 2.07 to 2.72) in men and IRR 2.15 (95% CI 1.77 to 2.61) in women. Having ongoing university studies was associated with a higher risk of suicide compared with having attained university-level education. This finding highlights the importance of achieving a deeper understanding of suicidal behaviour during years at university. Further studies should assess risk factors for suicide and suicidal behaviour in university students.


Resistance of medical gloves to permeation by methyl methacrylate (MMA), ethylene glycol dimethacrylate (EGDMA), and 1,4-butanediol dimethacrylate (1,4-BDMA).
Gloves afford hand protection by minimizing skin contact. The effectiveness of medical gloves to protect against permeation of the monomers, methyl methacrylate (MMA), ethylene glycol dimethacrylate (EGDMA), and 1,4-butanediol dimethacrylate (1,4-BDMA), was assessed focusing on permeation rates and degradation of glove materials caused by monomer contact. Fifteen different brands of gloves were tested using a European Standard procedure. Surface images of glove materials before and after exposure to the monomer mixture were obtained using a scanning electron microscope. The standard is not applicable as the only method for estimating the safety of gloves, but it is useful as guideline together with the cumulative permeation of acrylic monomers. Monomer contact on the outside resulted in substantial swelling of most glove materials, and structure changes of the inside surface.


Circulating immune complexes in tuberculosis.
Using a polyethylene glycol precipitation method, immune complexes were detected in 56% of patients with active tuberculosis. After antituberculous treatment, 29% remained positive for immune complexes, a frequency similar to that in a group of racially matched clinic controls (35%). In a study of 17 patients whose immune complex levels were determined soon after diagnosis and again when the therapy had ceased, there was a significant decrease in complexed IgM and Clq. Sequential studies of immune complex levels in tuberculosis merit further investigation, their persistence may indicate the continued presence of antigens, and their disappearance from the circulation may be a guide to successful treatment.


Current management of small cell lung cancer.
There will be approximately 45,000 new cases of small cell lung cancer (SCLC) this year. Despite the initial sensitivity to chemotherapy, only 10% of all SCLC patients will have significant long-term survival. Studies have yet to show significant survival advantage for maintenance chemotherapy, and it appears that four to six cycles of chemotherapy is as effective as longer durations of chemotherapy. There is as yet no defined role for dose increase in the treatment of SCLC. In extensive disease no one chemotherapy combination has shown a definitive survival advantage, although it appears that single-agent oral etoposide may be inferior to combination intravenous chemotherapy. In limited disease, however, cisplatin plus etoposide alone or in alternation with cyclophosphamide, doxorubicin, and vincristine is superior to other approaches. Also, in limited disease, chemotherapy plus radiotherapy is superior to chemotherapy alone and it appears that early concurrent radiotherapy may be the ideal approach. Myeloid growth factors should not be given concurrently with thoracic radiotherapy. There are several new agents with significant activity in SCLC awaiting further study.


Structure-activity relationships in a new class of non-substrate-like covalent inhibitors of the bacterial glycosyltransferase LgtC.
Lipooligosaccharide (LOS) structures in the outer core of Gram-negative mucosal pathogens such as Neisseria meningitidis and Haemophilus influenzae contain characteristic glycoepitopes that contribute significantly to bacterial virulence. An important example is the digalactoside epitope generated by the retaining α-1,4-galactosyltransferase LgtC. These digalactosides camouflage the pathogen from the host immune system and increase its serum resistance. Small molecular inhibitors of LgtC are therefore sought after as chemical tools to study bacterial virulence, and as potential candidates for anti-virulence drug discovery. We have recently discovered a new class of non-substrate-like inhibitors of LgtC. The new inhibitors act via a covalent mode of action, targeting a non-catalytic cysteine residue in the LgtC active site. Here, we describe, for the first time, structure-activity relationships for this new class of glycosyltransferase inhibitors. We have carried out a detailed analysis of the inhibition kinetics to establish the relative contribution of the non-covalent binding and the covalent inactivation steps for overall inhibitory activity. Selected inhibitors were also evaluated against a serum-resistant strain of Haemophilus influenzae, but did not enhance the killing effect of human serum.


Studies on the affinity of hyaluronic acid binding protein to glycosaminoglycans.
The affinity of hyaluronic acid binding protein (HBP) to different glycosaminoglycans (GAGs) was examined. The purified protein was pretreated with hyaluronic acid (HA), heparin, glucuronic acid and N-Acetyl-glucosamine and was loaded onto Hyaluronate-Sepharose affinity column. The binding of HBP to HA immobilized on sepharose column was specifically blocked only by pretreatment of HBP to HA and the elution of HBP was decreased proportionately with the addition of higher quantity of HBP. The specificity of HBP to HA was confirmed as it did not bind to Heparin-Sepharose or Chondroitin-4-Sulphate-Sepharose columns. The complex of HBP in association with HA was further shown on Sephadex G-200 and 7.5% polyacrylamide gel. All the experimental findings indicate that HBP binds specifically to HA only.


Do patients adhere to over-the-counter artemisinin combination therapy for malaria? evidence from an intervention study in Uganda.
Increasing affordability of artemisinin combination therapy (ACT) in the African retail sector could be critical to expanding access to effective malaria treatment, but must be balanced by efforts to protect the efficacy of these drugs. Previous research estimates ACT adherence rates among public sector patients, but adherence among retail sector purchasers could differ substantially. This study aimed to estimate adherence rates to subsidized, over-the-counter ACT in rural Uganda. An intervention study was conducted with four licensed drug shops in Eastern Uganda in December 2009. Artemether-lumefantrine (AL) was made available for sale at a 95% subsidy over-the counter. Customers completed a brief survey at the time of purchase and then were randomly assigned to one of three study arms: no follow-up, follow-up after two days or follow-up after three days. Surveyors recorded the number of pills remaining through blister pack observation or through self-report if the pack was unavailable. The purpose of the three-day follow-up arm was to capture non-adherence in the sense of an incomplete treatment course ("under-dosing"). The purpose of the two-day follow-up arm was to capture whether participants completed the full course too soon ("over-dosing"). Of the 106 patients in the two-day follow-up sample, 14 (13.2%) had finished the entire treatment course by the second day. Of the 152 patients in the three-day follow-up sample, 49 (32.2%) were definitely non-adherent, three (2%) were probably non-adherent and 100 (65.8%) were probably adherent. Among the 52 who were non-adherent, 31 (59.6%) had more than a full day of treatment remaining. Overall, adherence to subsidized ACT purchased over-the-counter was found to be moderate. Further, a non-trivial fraction of those who complete treatment are taking the full course too quickly. Strategies to increase adherence in the retail sector are needed in the context of increasing availability and affordability of ACT in this sector.


Adenine Sulfate Improves Cardiac Function and the Cardiac Cholinergic System After Myocardial Infarction in Rats.
Recent studies have shown that vagal activation may have an important therapeutic implication for myocardial infarction (MI), but effective strategies remain unexplored. Here, we investigate whether adenine sulfate can preserve cardiac function and the cholinergic system against MI. Rats were treated with adenine sulfate for three weeks after coronary ligation. Cardiac function was assessed by hemodynamics. The muscarinic M2 receptor and cholinesterase-positive nerves were semi-quantified by immunochemical and histochemical staining. The maximal binding capacity (Bmax) of muscarinic receptors, determined by radioligand binding assay, showed that cardiac function was impaired in MI rats. Adenine sulfate reversed MI-induced reduction of mean artery pressure and left ventricular systolic pressure and elevation of left ventricular end-diastolic pressure. Moreover, adenine sulfate also increased nitric oxide (NO) and nitric oxide synthase (NOS) activity. The amelioration was accompanied by a reversal of the infarction-induced reduction of cholinesterase-positive nerves and M2-receptor expression and Bmax in the adenine sulfate high dose group. Meanwhile, adenine sulfate treatment corrected the disorder of cardiac redox state by reduction in maleic dialdehyde and increase in superoxide dismutase. In conclusion, adenine sulfate exerts cardioprotection against MI and ameliorates NO production. Changes in cardiac vagal distribution density and M2-receptor expression raise the possibility that improvement of the cardiac cholinergic system is involved in adenine sulfate-induced cardioprotective effects.


Differentiation of benign and malignant lymph nodes with contrast-enhanced echolymphography using endoscopic ultrasound-guided puncture.
Although endoscopic ultrasonography is considered the most useful diagnostic modality for the regional staging, the capability of diagnosing lymph node metastasis based on endoscopic ultrasonography images alone is not sufficient. To improve the capability of differential diagnosis of lymph node enlargement, contrast-enhanced echolymphography was performed using endoscopic ultrasonography-guided puncture. Contrast-enhanced echolymphography was performed in 8 metastatic lymph nodes surgically resected from patients with gastrointestinal cancers (in vitro study) and also in 55 patients in whom abdominal lymph node swelling was indicated by endoscopic ultrasonography (in vivo study). Lymph nodes were punctured under real-time endoscopic ultrasonography guidance, and carbon dioxide microbubbles were injected to evaluate echo features before and after microbubbles injection. Contrast-enhanced echolymphography of freshly resected metastatic lymph nodes showed nonhomogeneous echo patterns. In regions demonstrating filling defects detected by contrast-enhanced echolymphography, neoplastic infiltration was pathologically observed. In almost all of the malignant lymph nodes studied in vivo, filling defects and heterogeneous enhancements were observed by contrast-enhanced echolymphography. However, contrast-enhanced echolymphography demonstrated uniform patterns in most of the benign group. The sensitivity, specificity, positive and negative predictive value, and accuracy of differential diagnosis by contrast-enhanced echolymphography were 95.8%, 90.3%, 88.5%, 96.6%, and 92.7%, respectively. Contrast-enhanced echolymphography is a useful method for help in the differentiation between reactive and malignant alterations of lymph nodes.


Differentiation between incomplete Kawasaki disease and secondary hemophagocytic lymphohistiocytosis following Kawasaki disease using N-terminal pro-brain natriuretic peptide.
Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome with many causes, including Kawasaki disease (KD). The purpose of this study was to identify the laboratory tests needed to easily differentiate KD with HLH from incomplete KD alone. We performed a retrospective study on patients diagnosed with incomplete KD and incomplete KD with HLH (HLH-KD) between January 2012 and March 2015. We compared 8 secondary HLH patients who were first diagnosed with incomplete KD with all 247 incomplete KD diagnosed patients during the study period. The complete blood count, erythrocyte sedimentation rate, platelet count, and serum total protein, albumin, triglyceride, C-reactive protein, N-terminal pro-brain natriuretic peptide (NT-proBNP), and ferritin levels were compared. Clinical characteristics and echocardiography findings were also compared between the 2 groups. The total duration of fever was longer in the HLH-KD group than in the KD group. White blood cell and platelet counts were higher in the KD group. Alanine aminotransferase, ferritin, and coronary artery diameter were increased in the HLH-KD group compared with those in the KD group. The median of NT-proBNP was significantly higher in the HLH-KD group than in the KD group at 889.0 (interquartile range [IQR], 384.5-1792.0) pg/mL vs. 233.0 (IQR, 107.0-544.0) pg/mL. The NT-proBNP level may be helpful in distinguishing incomplete KD from KD with HLH. The NT-proBNP level should be determined in KD patients with prolonged fever, in addition to the white blood cell count, platelet count, and ferritin level, to evaluate secondary HLH.


Markers of microbial translocation during pregnancy: differences among HIV+ women of African and European provenance.
Microbial translocation (MT) markers are indicators of HIV-related immune activation, but reference values are mostly derived from European or North American populations and could be substantially different in populations living in developing countries. Here we evaluate possible differences in MT markers levels in HIV+ pregnant women of different geographical provenance. This study is nested within an observational study of pregnant women with HIV in Italy. Women were dichotomized on the basis of provenance in two groups of European (n = 14) and African (n = 26) origin. Soluble CD14, lipopolysaccharide-binding protein (LBP) and intestinal-fatty acid binding protein (I-FABP) were measured in plasma samples collected between the first and second trimester of pregnancy. Demographic and viroimmunological characteristics were similar between groups, although European women were more commonly smokers and HCV-coinfected. Irrespective of origin, LBP plasma levels were positively correlated with I-FABP (r = 0.467, p = 0.004) and sCD14 levels (r = 0.312 p = 0.060). Significantly higher levels of sCD14 (1885 vs. 1208 ng/mL, p = 0.005) LBP (28.5 vs. 25.3 µg/mL, p = 0.050) and I-FABP (573.4 vs. 358.2 pg/mL, p = 0.002) were observed in European compared with African women. A multivariable linear regression analysis, adjusted for smoking and HCV coinfection confirmed the association between sCD14 levels and women provenance (p = 0.03). Our observations indicate significant differences in soluble markers among women of different provenance. In the design and analysis of studies evaluating MT markers, population-specific reference values should be considered.


Smooth muscle contraction bands in the media of coronary arteries: a postmortem marker of antemortem coronary spasm?
To date, no unequivocal morphologic markers have been described that would allow the diagnosis of coronary artery spasm to be made at autopsy. The coronary arteries of 63 adult patients without myocardial infarction were examined at autopsy, and the presence of medial smooth muscle contraction bands in these vessels was correlated with other vascular changes, myocardial pathologic changes and clinical history. These contraction bands have not been reported previously in human coronary arteries, but they were identified in experimental vascular spasm induced with catecholamines. It was found that 47 of the 63 cases were positive for contraction bands. As evidence of an antemortem process, there was a significant correlation between these changes and the presence of nonocclusive microthrombi, found in 25 cases. Contraction bands were also highly correlated with atherosclerotic plaque ruptures and mural plaque hemorrhages, which may be secondary to coronary spasm. In 78.7% of the cases positive for contraction bands, the cause of death was related to a diagnosis possibly associated with high catecholamine levels. On the basis of experimental evidence and the correlations identified in this study, coronary artery medial smooth muscle contraction bands may represent a postmortem marker of antemortem coronary spasm.


Baclofen selectively inhibits transmission at synapses made by axons of CA3 pyramidal cells in the hippocampal slice.
The effects of baclofen, an antispastic drug, on excitatory transmission were tested by bath application to the hippocampal slice preparation. (+/-)-Baclofen (20 microM) strongly depressed extracellularly recorded synaptic responses to stimulation of projections that originate from CA3 hippocampal pyramidal cells. Responses to stimulation of four other excitatory pathways were little affected and the amplitudes of presynaptic fiber potentials and antidromic responses were unaltered. When tested on the Schaffer collateral-commissural-CA1 pyramidal cell synapse. (-)-baclofen depressed the amplitude of the extracellular excitatory postsynaptic potential with an IC50 of 3.7 microM and was 180 times more potent than (+)-baclofen. gamma-Aminobutyric acid, 3-aminopropanesulfonic acid and imidazole-4-acetic acid also inhibited transmission at this site. Baclofen could suppress the response completely, and its action was unaffected by bicuculline. In contrast, imidazole-4-acetic acid could suppress the response by a maximum of only 75%, and its action was highly sensitive to bicuculline. gamma-Aminobutyric acid and 3-aminopropanesulfonic acid could suppress the response completely, and their actions were relatively weakly antagonized by bicuculline. These results are consistent with the hypothesis that baclofen inhibits excitatory transmission by interacting with a bicuculline-insensitive gamma-aminobutyric acid receptor. These receptors may be located on one type of glutamatergic/aspartergic synaptic terminal, exemplified by axon terminals of CA3 hippocampal pyramidal cells. Synapses made by these axons may therefore serve as models for studying the mechanism of action of baclofen.


Molecular bases of circadian rhythmicity in renal physiology and pathology.
The physiological processes that maintain body homeostasis oscillate during the day. Diurnal changes characterize kidney functions, comprising regulation of hydro-electrolytic and acid-base balance, reabsorption of small solutes and hormone production. Renal physiology is characterized by 24-h periodicity and contributes to circadian variability of blood pressure levels, related as well to nychthemeral changes of sodium sensitivity, physical activity, vascular tone, autonomic function and neurotransmitter release from sympathetic innervations. The circadian rhythmicity of body physiology is driven by central and peripheral biological clockworks and entrained by the geophysical light/dark cycle. Chronodisruption, defined as the mismatch between environmental-social cues and physiological-behavioral patterns, causes internal desynchronization of periodic functions, leading to pathophysiological mechanisms underlying degenerative, immune related, metabolic and neoplastic diseases. In this review we will address the genetic, molecular and anatomical elements that hardwire circadian rhythmicity in renal physiology and subtend disarray of time-dependent changes in renal pathology.


Replacement of adenylate cyclase toxin in a lineage of Bordetella bronchiseptica.
Bordetella bronchiseptica is a gram-negative respiratory pathogen that infects a wide range of hosts and causes a diverse spectrum of disease. This diversity is likely affected by multiple factors, such as host immune status, polymicrobial infection, and strain diversity. In a murine model of infection, we found that the virulence of B. bronchiseptica strains, as measured by the mean lethal dose, varied widely. Strain 253 was less virulent than the typically studied strain, RB50. Transcriptome analysis showed that cyaA, the gene encoding adenylate cyclase toxin (CyaA), was the most downregulated transcript identified in strain 253 compared to that in strain RB50. Comparative genomic hybridization and genome sequencing of strain 253 revealed that the cya locus, which encodes, activates, and secretes CyaA, was replaced by an operon (ptp) predicted to encode peptide transport proteins. Other B. bronchiseptica strains from the same phylogenetic lineage as that of strain 253 also lacked the cya locus, contained the ptp genes, and were less virulent than strain RB50. Although the loss of CyaA would be expected to be counterselected since it is conserved among the classical bordetellae and believed to be important to their success, our data indicate that the loss of this toxin and the gain of the ptp genes occurred in an ancestral strain that then expanded into a lineage. This suggests that there may be ecological niches in which CyaA is not critical for the success of B. bronchiseptica.


Effects of dietary marjoram, Origanum majorana extract on growth performance, hematological, antioxidant, humoral and mucosal immune responses, and resistance of common carp, Cyprinus carpio against Aeromonas hydrophila.
The present study aimed to investigate the potential effects of dietary marjoram extract on growth performance, health, and disease resistance in common carp, Cyprinus carpio. To this purpose, the fish were assigned into four treatments and fed by diets supplemented with 0 (control), 100, 200, and 400 mg marjoram extract kg-1 over eight weeks and then challenged with Aeromonas hydrophila. According to the results, 200 mg kg-1 dietary marjoram extract inclusion showed the highest final weight, weight gain, and specific growth rate, and lowest feed conversion ratio (FCR). White blood cell number, Red blood cells, hematocrit, hemoglobin, mean corpuscular volume and mean corpuscular hemoglobin were markedly increased particularly at 200 mg kg-1 treatment. Marjoram extract significantly increased plasma superoxide dismutase activity and decreased malondialdehyde level compared to the control treatment. Plasma complement and lysozyme activities and total immunoglobulin levels, mucosal complement, lysozyme and alkaline phosphatase activities and immunoglobulin levels were significantly increased compared to the control group. The lowest post-challenge survival rate was observed in the control treatment, whereas the highest value was related to the 200 mg kg-1 marjoram treatment. In conclusion, the present study demonstrated that, marjoram extract is a suitable feed supplements for common carp, as it stimulates the fish growth, antioxidant, and immune systems, which suppress the fish mortality during Aeromonas septicemia. According to the results, 200 mg marjoram extract kg-1 is recommended for carp feed formulation.


Mutation update for the PORCN gene.
Mutations in the PORCN gene were first identified in Goltz-Gorlin syndrome patients in 2007. Since then, several reports have been published describing a large variety of genetic defects resulting in the Goltz-Gorlin syndrome, and mutations or deletions were also reported in angioma serpiginosum, the pentalogy of Cantrell and Limb-Body Wall Complex. Here we present a review of the published mutations in the PORCN gene to date and report on seven new mutations together with the corresponding clinical data. Based on the review we have created a Web-based locus-specific database that lists all identified variants and allows the inclusion of future reports. The database is based on the Leiden Open (source) Variation Database (LOVD) software, and is accessible online at http://www.lovd.nl/porcn. At present, the database contains 106 variants, representing 68 different mutations, scattered along the whole coding sequence of the PORCN gene, and 12 large gene rearrangements, which brings up to 80 the number of unique mutations identified in Goltz-Gorlin syndrome patients.


The Schizophrenia Patient Outcomes Research Team (PORT): updated treatment recommendations 2009.
The Schizophrenia Patient Outcomes Research Team (PORT) project has played a significant role in the development and dissemination of evidence-based practices for schizophrenia. In contrast to other clinical guidelines, the Schizophrenia PORT Treatment Recommendations, initially published in 1998 and first revised in 2003, are based primarily on empirical data. Over the last 5 years, research on psychopharmacologic and psychosocial treatments for schizophrenia has continued to evolve, warranting an update of the PORT recommendations. In consultation with expert advisors, 2 Evidence Review Groups (ERGs) identified 41 treatment areas for review and conducted electronic literature searches to identify all clinical studies published since the last PORT literature review. The ERGs also reviewed studies preceding 2002 in areas not covered by previous PORT reviews, including smoking cessation, substance abuse, and weight loss. The ERGs reviewed over 600 studies and synthesized the research evidence, producing recommendations for those treatments for which the evidence was sufficiently strong to merit recommendation status. For those treatments lacking empirical support, the ERGs produced parallel summary statements. An Expert Panel consisting of 39 schizophrenia researchers, clinicians, and consumers attended a conference in November 2008 in which consensus was reached on the state of the evidence for each of the treatment areas reviewed. The methods and outcomes of the update process are presented here and resulted in recommendations for 16 psychopharmacologic and 8 psychosocial treatments for schizophrenia. Another 13 psychopharmacologic and 4 psychosocial treatments had insufficient evidence to support a recommendation, representing significant unmet needs in important treatment domains.


Health effects of home energy efficiency interventions in England: a modelling study.
To assess potential public health impacts of changes to indoor air quality and temperature due to energy efficiency retrofits in English dwellings to meet 2030 carbon reduction targets. Health impact modelling study. England. English household population. Three retrofit scenarios were modelled: (1) fabric and ventilation retrofits installed assuming building regulations are met; (2) as with scenario (1) but with additional ventilation for homes at risk of poor ventilation; (3) as with scenario (1) but with no additional ventilation to illustrate the potential risk of weak regulations and non-compliance. Primary outcomes were changes in quality adjusted life years (QALYs) over 50 years from cardiorespiratory diseases, lung cancer, asthma and common mental disorders due to changes in indoor air pollutants, including secondhand tobacco smoke, PM2.5 from indoor and outdoor sources, radon, mould, and indoor winter temperatures. The modelling study estimates showed that scenario (1) resulted in positive effects on net mortality and morbidity of 2241 (95% credible intervals (CI) 2085 to 2397) QALYs per 10,000 persons over 50 years follow-up due to improved temperatures and reduced exposure to indoor pollutants, despite an increase in exposure to outdoor-generated particulate matter with a diameter of 2.5 μm or less (PM₂.₅). Scenario (2) resulted in a negative impact of -728 (95% CI -864 to -592) QALYs per 10,000 persons over 50 years due to an overall increase in indoor pollutant exposures. Scenario (3) resulted in -539 (95% CI -678 to -399) QALYs per 10,000 persons over 50 years follow-up due to an increase in indoor exposures despite the targeting of pollutants. If properly implemented alongside ventilation, energy efficiency retrofits in housing can improve health by reducing exposure to cold and air pollutants. Maximising the health benefits requires careful understanding of the balance of changes in pollutant exposures, highlighting the importance of ventilation to mitigate the risk of poor indoor air quality.


Load-Independent Characterization of Plate Foundation Support Using High-Resolution Distributed Fiber-Optic Sensing.
The evaluation of soil reaction in geotechnical foundation systems such as concrete pavements, mat- and raft foundations is a challenging task, as the process involves both the selection of a representative mechanical model (e.g., Winkler, Continuum, Pasternak, etc.) and identify its prevailing parameters. Moreover, the support characteristics may change with time and environmental situation. This paper presents a new method for the characterization of plate foundation support using high-resolution fiber-optic distributed strain sensing. The approach involves tracking the location of distinct points of zero and maximum strains, and relating the shift in their location to the changes in soil reaction. The approach may allow the determination of the most suited mechanical model of soil representation as well as model parameters. Routine monitoring using this approach may help to asses the degradation of the subsoil with time as part of structural health monitoring strategies. In this paper, fundamental expressions that relate between the location of distinct strain points and the variation of soil parameters were developed based on various analytical foundation support models. Finally, as an initial validation step and to underpin the idea basics, the proposed method was successfully demonstrated on a simple mechanical setup. It is shown that the approach allows for load-independent characterization of the soil response and, in that sense, it is superior to common identification methods.


MRI in rolandic epilepsy.
Hippocampal and/or white matter abnormalities have been found on the MRIs in 10/18 children with typical rolandic epilepsy. The etiology of the first-mentioned is not evident, whereas the latter may be a result of a maturational delay involving a defective myelination. Both abnormalities may cause cognitive dysfunction. In order to get a better understanding of rolandic epilepsy both MRI and neuropsychological studies are wanted in groups of children with typical rolandic seizures with and without rolandic sharp waves, as well as in groups of children with typical rolandic sharp waves and atypical seizures.


[Improved method of dermatoplasty].
For restoration of dermal integument on hands, feet, major joints, face and neck in 104 patients special device was used which provided creation of split dermal flaps of new types--with fenestrated gaping perforations or entire flaps with areas of various thickness which enabled to preserve islands of full thickness skin at donor's sites or superficial dermal layers. The thickness of the transplants made up 0.4-0.6 mm in adults and 0.25-0.5 mm in children. Perforated flaps were transplanted in 128 cases, the flaps of variable thickness--in 31. 151 operations (95.0%) resulted in complete recovering of the transplants, all wounds at donor's sites have closed spontaneously. Through 3-17 years after the operation the scars at perforations' sites looked hardly out of the ordinary, the areas of smaller thickness are unnoticeable, skin-grafts are soft and loading-proofed. The decrease in complications' rate and improvement of functional and aesthetic results of treatment after the application of the device were stated.


[Temporal changes and determinants of smoking habits with respect to prevention].
Smoking habits are seen as one of the most important risk factors in developed countries for the incidence of cardiovascular diseases and as the major single cause of premature death. The present study analysed smoking habits in participants of the MONICA-Surveys S1 (1984/85), S2 (1989/90) and S3 (1994/95) concerning prevalence, associated factors, time trends and preventive consequences. An essential aim of these studies was to identify risk groups, that should be addressed in prevention campaigns leading to a reduction of the high mortality due to cardiovascular diseases. The participants of the MONICA-Survey S3 (1994/95) had lower proportions of smokers (31.2 % for men and 22.0 % for women) as compared to estimated proportions of the entire German population (National health survey 1998: 37.4 % und 29.9 %). Women had always a lower proportion of smokers than men in each age group or sociodemographic factor. Strong associations of smoking habits with educational levels, family status and occupational position were observed for men and women. A positive time trend with decreasing smoking prevalence was determined for men. In contrast, an increase in the prevalence of female smokers was observed. The intention to change smoking habits was associated with different factors in men and women. For men, mainly "external" factors like social status or physical activity were important. Women seemed to be more influenced by "internal" matters (somatic complaints, negative self-rated health). Sex-, age- and educational status-specific activities and recommendations are considered to be essential for targeting different person groups in a more focused way.


Measurement of Yersinia Translocon Pore Formation in Erythrocytes.
Many Gram-negative pathogens produce a type III secretion system capable of intoxicating eukaryotic cells with immune-modulating effector proteins. Fundamental to this injection process is the prior secretion of two translocator proteins destined for injectisome translocon pore assembly within the host cell plasma membrane. It is through this pore that effectors are believed to travel to gain access to the host cell interior. Yersinia species especially pathogenic to humans and animals assemble this translocon pore utilizing two hydrophobic translocator proteins-YopB and YopD. Although a full molecular understanding of the biogenesis, function and regulation of this translocon pore and subsequent effector delivery into host cells remains elusive, some of what we know about these processes can be attributed to studies of bacterial infections of erythrocytes. Herein we describe the methodology of erythrocyte infections by Yersinia, and how analysis of the resultant contact-dependent hemolysis can serve as a relative measurement of YopB- and YopD-dependent translocon pore formation.


Earlier joint trajectories of cigarette smoking and low perceived self-control as predictors of later poor health for women in their mid-60s.
The current study was designed to assess the prospective relationship between the earlier joint trajectories of cigarette smoking and low perceived self-control (X age = 40-48) and later health problems (X age = 65.2) within a community sample of understudied females. The participants were given self-administered questionnaires. The results of the growth mixture model suggested 5 joint trajectories of cigarette smoking and perceived self-control, which consisted of 1 at-risk group (chronic smoking and low perceived self-control), 1 low-risk group (infrequent or nonsmoking and high perceived self-control), and 3 intermediate groups (i.e., high on one factor and low on the other). The results from logistic regression analyses supported a model by which (a) women in the at-risk group, in comparison with the low-risk group, were more likely to report 5 or more diseases (adjusted odds ratio [AOR] = 4.81; p < .001) and poor or very poor general health (AOR = 5.98; p < .001); (b) women in the at-risk group as compared with women in the intermediate groups were also more likely to report 5 or more diseases (AOR = 2.36; p < .05) and poor or very poor general health (AOR = 2.86; p < .01); and (c) women in the intermediate group were more likely to report 5 or more diseases (AOR = 2.04; p < .05) and poor or very poor general health (AOR = 2.09; p < .05) than women in the low-risk group. The findings highlight the significance of targeting dispositional factors (e.g., perceived self-control) in conjunction with smoking in designing programs for promoting the health of women in midlife.


Detection of multiple sclerosis with visual evoked potentials--an unsupervised computational intelligence system.
This paper describes the application of a novel unsupervised pattern recognition system to the classification of the Visual Evoked Potentials (VEP's) of normal and multiple sclerosis (MS) patients. The method combines a traditional statistical feature extractor with a fuzzy clustering method, all implemented in a parallel neural network architecture. The optimization routine, ALOPEX, is used to train the network while decreasing the likelihood of local solutions. The unsupervised system includes a feature extraction and clustering module, trained by the optimization routine ALOPEX. Through maximization of the output variance of each node, and an architecture which excludes redundancy, the feature extraction network retains the most significant Karhunen-Loeve expansion vectors. The clustering module uses a modification to the Fuzzy c-Means (FCM) clustering algorithms, where ALOPEX adjusts a set of cluster centers to minimize an objective error function. The result combines the power of the FCM algorithms with the advantage of a more global solution from ALOPEX. The new pattern recognition system is used to cluster the VEP's of 13 normal and 12 MS subjects. The classification with this technique can, without supervision, separate the patient population into two groups which largely correspond to the MS and control subject groups. A suitable threshold can be chosen so that the recognizer chooses no false negatives. The use of multiple stimulation patterns appears to improve the reliability of the decision. The reasoning of most neural networks in their decision making cannot easily be extracted upon the completion of training. However, due to the linearity of the network nodes, the cluster prototypes of this unsupervised system can be reconstructed to illustrate the reasoning of the system. In this application, this analysis hints at the usefulness of previously unused portions of the VEP in detecting MS. It also indicates a possible use of the system as a training aide.


Using a mesocosm approach to evaluate marine benthic assemblage alteration associated with CO2 enrichment in coastal environments.
The effects of acidification related to the CO2 enrichment in the coastal environments on marine macrobenthic abundance, diversity and richness were analyzed in a medium- term (21 days) using mesocosm experiments. Two sampling sites located in the Bay of Cadiz - SW, Spain were selected and tested at pH values ranged from 7.9 to 6.0 (± 0.1). Moreover, variations in the concentrations of metals in the sediment samples were analyzed at the end of each experiment. The results showed low variation in the concentrations of metals in the sediment among the pH treatments. A significant decrease (p < 0.05) in the abundance, diversity and richness of assemblages were measured between the control and the lowest pH level in both sampling sites tested in this study (Rio San Pedro and El Trocadero). The majority of species were found in all samples except in pH 6.0 which only two species were found (Hydrobia ulvae and Scrobicularia plana,) in Rio San Pedro sediment fauna. In general, the results of cluster analysis showed 60% and 40% similarity in all replicated tests in El Trocadero and Rio San Pedro of sediment fauna, respectively. The results of the Principal Component Analysis (PCA) showed that both sediment parameters and pH reduction can interfere in the benthic assemblage indices. Although the assemblages' indices have shown decreases only in the lower pHs, the organisms also could be impacted by chronic effects. Therefore, the extension of this study is important in order to improve the knowledge about the risks associated with CO2 enrichment in on marine organisms.


Urinary biomarkers in patients with detrusor underactivity with and without bladder function recovery.
Detrusor underactivity (DU) is frequently encountered in elderly patients. Part of patients with DU might have bladder function recovery after treatment. This study investigated urinary proteins in these DU patients with and without bladder function recovery. A total of 37 patients with chronic urinary retention and urodynamically proven DU were enrolled. After treatment, 24 DU patients had bladder function recovery whereas 13 had not, after 1-year follow-up. Urine collection at baseline was performed, and the urinary protein including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and prostaglandin E2 (PGE2) were measured by ELISA. Twenty urodynamically normal, 34 detrusor overactivity (DO) and 15 detrusor hyperactivity and inadequate contractility (DHIC) patients served as comparative groups. Urinary NGF levels were significantly higher than normal in patients with DU (9.2 ± 20.3 vs 1.85 ± 2.9 pg/ml, p = 0.037). Urinary BDNF level was only significantly higher in patients with DU than that of the control group (153 ± 199 vs 77.4 ± 47.7 pg/ml, p = 0.033) but not in patients with DHIC or DO. Compared with the control group, the urinary BDNF level was significantly higher in DU patients with bladder function recovery (190 ± 239 pg/ml, p = 0.033) but not in patients without recovery (85.8 ± 43.7 pg/ml, p = 0.612). The PGE2 level was significantly higher than the control group in DU patients with bladder function recovery (1290 ± 836 pg/ml, p < 0.0001) but not in patients without recovery (383 ± 237 pg/ml, p = 0.130). Patients with DU and higher urinary PGE2 and BDNF levels might have a chance to recover bladder function than those with a lower protein level.


[A system for non-invasive measurement of arterial pulse velocity in different vascular territories].
Blood pulse wave velocity (PWV) is a known index of arterial rigidity and its measurement has proved its usefulness in the study of some cardiovascular pathologies. In this study we describe the design and implementation of a system for noninvasive PWV determination in the aorto-braqui-humero-radial (A-->h), aorto-ileo-femoro-pedial (A-->f) and aorto-carotid (A-->c) regions. This system was examined with 36 normotensives (NT) and 34 hypertensives (HT) patients with (LVH, n = 20) and without (WLVH, n = 14) left ventricular hypertrofy. The equipment consist of a personal computer with an analog to digital converter and hardware and software items adapted to take simultaneously the electrocardiogram (ECG), two photopletismographic pulses and one oscilometric pulse. The Q-pP interval (time between a Q ECG wave and distal blood pulse) and the distance to the register sites are taken into account to calculate the beginning of cardiac prexpulsive period (time zero of pulse trip) which allow the determination of the PWV (in meters/second) from the aortic root to the distal point of the via. PWV was significant higher (p < 0.001) in HT vs. NT (A-->h: 9.3 +/- 2.6 vs. 7.2 +/- 0.8, A-->c: 9.5 +/- 2.8 vs. 6.0 +/- 1.9 and A-->f: 9.5 +/- 1.8 vs. 7.2 +/- 0.9) in each evaluated arterial region. Same thing occurred in cases with LVH vs. WLVH (A-->h: 10.5 +/- 1.6 vs. 8.0 +/- 1.9, A-->c: 10.2 +/- 1.9 vs. 8.0 +/- 1.9 and A-->f: 10.5 +/- 2.0 vs. 8.6 +/- 1.2) (p < 0.025). This is consistent with the relationship more pressure [symbol: see text] more rigidity and with other reports. This method may have clinical application.


Parkin Coordinates Platelet Stress Response in Diabetes Mellitus: A Big Role in a Small Cell.
Increased platelet activation and apoptosis are characteristic of diabetic (DM) platelets, where a Parkin-dependent mitophagy serves a major endogenous protective role. We now demonstrate that Parkin is highly expressed in both healthy platelets and diabetic platelets, compared to other mitochondria-enriched tissues such as the heart, muscle, brain, and liver. Abundance of Parkin in a small, short-lived anucleate cell suggest significance in various key processes. Through proteomics we identified 127 Parkin-interacting proteins in DM platelets and compared them to healthy controls. We assessed the 11 highest covered proteins by individual IPs and confirmed seven proteins that interacted with Parkin; VCP/p97, LAMP1, HADHA, FREMT3, PDIA, ILK, and 14-3-3. Upon further STRING analysis using GO and KEGG, interactions were divided into two broad groups: targeting platelet activation through (1) actions on mitochondria and (2) actions on integrin signaling. Parkin plays an important role in mitochondrial protection through mitophagy (VCP/p97), recruiting phagophores, and targeting lysosomes (with LAMP1). Mitochondrial β-oxidation may also be regulated by the Parkin/HADHA interaction. Parkin may regulate platelet aggregation and activation through integrin signaling through interactions with proteins like FREMT3, PDIA, ILK, and 14-3-3. Thus, platelet Parkin may regulate the protection (mitophagy) and stress response (platelet activation) in DM platelets. This study identified new potential therapeutic targets for platelet mitochondrial dysfunction and hyperactivation in diabetes mellitus.


Electrical characteristics of inward-rectifying K+ channels in isolated bullfrog oxyntic cells.
The properties of K+ channels in the isolated oxyntic cells of the bullfrog (Rana catesbeiana) were investigated using the patch-clamp method. Two types of K+ channels on the basolateral membrane were identified on the basis of their electrophysiological and pharmacological properties. The K+ channel most frequently observed has a single-channel conductance of 61.0 +/- 2.9 pS (n = 10) and is activated by an increase in intracellular Ca2+. The other K+ channel has a single-channel conductance of 30.3 +/- 2.7 pS (n = 7), which is activated by adenosine 3',5'-cyclic monophosphate (cAMP). The physiological and pharmacological characteristics common to the two K+ channels are inward-going rectification with a high selectivity for K+ and indirect inhibition by omeprazole. The inward rectification is controlled by intracellular Mg2+ in such a way that the more Mg2+ is applied intracellularly, the more their inward-rectifying property is enhanced. The finding that bethanechol and cAMP increase the open probability of these K+ channels as well as activating the acid secretion indicates that there may be a relationship between these two processes in the oxyntic cells.


Distinct roles of age and abdominal visceral fat in reducing androgen receptor-dependent negative feedback on LH secretion in healthy men.
Testosterone (T) impacts luteinizing hormone (LH) secretion through negative feedback via the androgen receptor (AR) in the hypothalamo-pituitary system. An untested postulate is that increasing body mass index (BMI), abdominal visceral fat (AVF) or total abdominal fat (TAF) with ageing decreases LH secretion by heightening T negative feedback via AR. This hypothesis was tested in a prospective, randomized double-blind cross-over study of 19 healthy men comparing the effects of flutamide, a selective non-steroidal AR antagonist and placebo administration on basal and pulsatile LH secretion as a function of age and obesity measures. To this end, serum levels of 2-hydroxyflutamide (2-OHF), a major active flutamide metabolite, were measured by mass spectrometry, and AVF/TAF quantified by abdominal computerized tomography. Statistical analysis showed that antiandrogen administration elevated 6-h mean LH concentrations to 5.4 ± 1.3 IU/L compared with 3.3 ± 1.2 IU/L for placebo (p < 10(-3) ), and total T by 35% (p < 10(-4) ). The LH-T concentration product doubled (p < 10(-8) ). According to deconvolution analysis, flutamide exposure increased total LH secretion (p < 10(-3) ) and pulsatile LH secretion (p = 0.0077), along with LH pulse frequency (p = 0.019). Despite feedback inhibition, the LH-T product declined as a linear function of AVF (p = 0.021) and TAF (p = 0.017). This was explained by the fact that higher BMI was associated with lower 2-OHF concentrations (R = -0.562, p = 0.012). In contrast, age was associated with less pulsatile LH secretion (R = -0.567, p = 0.011) even when LH responses were normalized to antiantrogen levels. In conclusion, increased AVF, TAF and BMI predict decreased LH and flutamide blood levels, whereas older age is marked by impaired stimulation of pulsatile LH secretion even when normalized for antiandrogen levels, suggesting different mechanisms of regulation by adiposity and age.


Venous compression at high-spatial-resolution three-dimensional MR angiography of peripheral arteries.
The aim of this study was to assess a venous compression technique that is performed with contrast material-enhanced peripheral magnetic resonance (MR) angiography to reduce venous enhancement. Healthy volunteers, as well as patients with correlating digital subtraction angiographic (DSA) findings, were examined. Venous compression was accomplished by placing a cuff at the midfemoral level unilaterally. Arterial signal-to-noise and contrast-to-noise ratios indicated no significant differences between compressed and noncompressed legs. Venous overlay was substantially reduced in the compressed legs. MR angiography with venous compression yielded diagnostic image quality and results that had excellent correlation with DSA findings. High-spatial-resolution peripheral MR angiography of improved diagnostic quality appears feasible, even with long data acquisition times.


[Comparative efficacy of the laparotomic and laparoscopic operative procedures in patients with an acute biliary pancreatitis].
Comparative estimation of the laparotomic and laparoscopic operative interventions efficacy was done in 75 patients with an acute biliary pancreatitis. In control group included 39 patients, operated using laparotomic access, in main group--36 patients, in which was done diagnostic and medical laparoscopic interventions. Application of laparoscopy have allowed to establish diagnosis, form of disease, presence of peritonitis and determinate medical tactics. In emergent order operated 8 (22.2%) patients with acute phlegmonous cholecystitis in combination with noninfected pancreatonecrosis. In 28 (77.8%) patients were performed medical laparoscopic interventions with endoscopic papillosphincterotomy.


Urinalysis and electrolyte profiles in patients with acquired immunodeficiency syndrome.
One hundred and twenty six patients diagnosed as having AIDS had their urinalysis and electrolyte profiles studied. The commonest electrolyte abnormalities were a low serum bicarbonate in 56% of the patients and hyponatraemia in 48%. Possible aetiological factors are discussed. Significant pyuria was found in 10% of the patients and significant bacteriuria in 13%. Escherichia coli was the commonest isolated organism (56% of all the culture positive cases). Proteinuria above the upper limit of normal was detectable in 13% of the patients; of these, 25% had proteinuria in the nephrotic range. Of the patients 3% had clinical and biochemical evidence of renal insufficiency. It is concluded that significant bacteriuria occurs commonly in AIDS and that renal insufficiency and nephrotic syndrome may be associated with the disease. It is also noted that other electrolyte and acid-base abnormalities, in particular hyponatraemia and low bicarbonate levels may contribute to the morbidity and mortality in patients suffering from AIDS.


"This is a Pakhtun disease": Pakhtun health journalists' perceptions of the barriers and facilitators to polio vaccine acceptance among the high-risk Pakhtun community in Pakistan.
Pakistan is one of only three poliomyelitis-endemic countries in the world. Twelve wild poliovirus (WPV) cases were recorded in the country in 2018. Even though resistance to oral polio vaccine (OPV) has decreased over time, there are still pockets of communities, mostly ethnic Pakhtun living in the Khyber Pakhtunkhwa (KP) province, that resist OPV. Although local journalists may be important sources of health information, past studies have overlooked their role in this context. The purpose of this study was to examine Pakhtun health journalists' beliefs regarding OPV and their views of the barriers and facilitators that influence OPV acceptance or hesitancy in their communities. We recruited and interviewed 33 Pakhtun journalists covering health issues for diverse media outlets in high-risk districts for WPV of the KP province. The semi-structured interviews were translated, transcribed, and analyzed for themes. The participants strongly supported OPV and advocated that children in their own families and communities get vaccinated against polio. At the same time, they felt that their communities faced more urgent health needs that were not addressed by the government. They identified barriers at the media organizational level operating against accurate coverage of OPV, including financial and time constraints, a lack of checks and balances, and limited health literacy. They regarded press releases issued by the officials associated with OPV campaigns as the main facilitators in the coverage of OPV. The participants perceived lack of community trust in the government, security concerns, and community members' religious beliefs as the major impediments to increase in uptake of OPV. Pakhtun health journalists have the potential to be important partners in national polio eradication initiatives. They should receive culturally sensitive training in local languages at appropriate literacy levels. We also suggest direct involvement of journalists in community mobilization efforts.


Imaging properties of three refractive axicons.
The imaging properties of three types of refractive axicons are examined by using them in an imaging system. A linear axicon, a logarithmic axicon, and a Fresnel axicon are characterized by determining their point spread functions (PSFs) experimentally and by numerical simulation. The PSFs, which vary along the depth of field for the cases considered in the present investigation, are used in digital filters to denoise the images. A comparison of the imaging performance of these three optical elements is presented.


The utility of decompressive craniectomy in severe traumatic brain injury in Saudi Arabia trauma centers.
Background: Decompressive craniectomy (DC) represents an effective method for intracranial pressure (ICP) reduction in cases of severe traumatic brain injury (TBI). However, little is known regarding the attitude of practicing neurosurgeons toward decompressive craniectomy (DC) in Saudi Arabia.Objective: We aimed to explore the perspective on DC among neurosurgeons in Saudi Arabia.Methods: An electronic survey was distributed via e-mail to members of the Saudi Association of Neurological Surgery (SANS).Results: A total of 52 neurosurgeons participated in this survey. The majority of these neurosurgeons practice in a governmental (95.2%), tertiary hospital (75.5%) with academic affiliations (77.6%). Most surgeons (71.4%) agreed that the DC approach for managing refractory ICP is supported by evidence-based medicine. The majority of the participants choose to perform DC on a unilateral basis (80%). Interestingly, DC followed by duraplasty was performed by only 71% of these surgeons, with 29% of the respondents not performing expansive duraplasty.Conclusion: In Saudi Arabia, the utility of DC in cases of TBI with refractory intracranial hypertension has not been clearly defined among practicing neurosurgeons. The development of appropriate, widely adopted TBI guidelines should thus be a priority in Saudi Arabia to reduce variability among TBI care practices. In addition, a national TBI registry should be established for documenting different practices and longitudinal outcomes.