RCN4GSC Workshop Report: Modeling a Testbed for Managing Data at the Interface of Biodiversity and (Meta)Genomics, April 2011.
At the GSC11 meeting (4-6 April 2011, Hinxton, England, the GSC's genomic biodiversity working group (GBWG) developed an initial model for a data management testbed at the interface of biodiversity with genomics and metagenomics. With representatives of the Global Biodiversity Information Facility (GBIF) participating, it was agreed that the most useful course of action would be for GBIF to collaborate with the GSC in its ongoing GBWG workshops to achieve common goals around interoperability/data integration across (meta)-genomic and species level data. It was determined that a quick comparison should be made of the contents of the Darwin Core (DwC) and the GSC data checklists, with a goal of determining their degree of overlap and compatibility. An ad-hoc task group lead by Renzo Kottman and Peter Dawyndt undertook an initial comparison between the Darwin Core (DwC) standard used by the Global Biodiversity Information Facility (GBIF) and the MIxS checklists put forward by the Genomic Standards Consortium (GSC). A term-by-term comparison showed that DwC and GSC concepts complement each other far more than they compete with each other. Because the preliminary analysis done at this meeting was based on expertise with GSC standards, but not with DwC standards, the group recommended that a joint meeting of DwC and GSC experts be convened as soon as possible to continue this joint assessment and to propose additional work going forward.


Acute terminal ileitis associated with pneumococcal bacteremia: case report and review of pneumococcal gastrointestinal diseases.
In this report, we describe a patient with acute terminal ileitis due to Streptococcus pneumoniae, review 3 previously reported cases of isolated enteritis due to S. pneumoniae, and summarize the English-language literature on primary and secondary pneumococcal gastrointestinal diseases. Various theories have been advanced to explain the pathogenesis of this rare and potentially life-threatening form of pneumococcal infection, but the mechanism by which S. pneumoniae causes gastrointestinal disease is still unknown.


Targeting PIK3CG in Combination with Paclitaxel as a Potential Therapeutic Regimen in Claudin-Low Breast Cancer.
Molecular targeting is a powerful approach for aggressive claudin-low breast cancer (CLBC). Overexpression of PI3K catalytic subunit gamma (PIK3CG) in human CLBC is offering a promising opportunity for targeted therapies. We utilized a specific inhibitor of PIK3CG combined with paclitaxel (PTX) to treat CLBC cells in vitro and in vivo. The tumor cells growth and apoptosis in vitro were analyzed by CCK8, plate clone formation assay, tumorsphere assay, Hoechst staining and flow cytometry. The invasion and metastasis ability of tumor cells in vitro were investigated by wound healing and transwell experiments. Critical gene expression levels were checked by qRT-PCR and Western blot. Xenograft models with CLBC cell lines in SCID mice were established to investigate the effect of combined drugs in vivo. We identified that PIK3CG was a potential therapeutic target for CLBC patients. Targeting PIK3CG potentiated CLBC cells growth inhibition in 2D and 3D cultures by PTX. Inhibition of PIK3CG activation could enhance CLBC cells apoptosis and migration suppression induced by PTX. Manipulating autophagy was a validated approach for the use of PIK3CG inhibitor. Using CLBC xenograft mice model, we found that CLBC tumors in vivo could be well treated by combined drugs of PIK3CG inhibitor and PTX. We demonstrated that PIK3CG was a potential target for the therapy of CLBC and inhibition of PIK3CG activation could reinforce the therapeutic effect of this aggressive disease by PTX. The combined use of PIK3CG inhibitor and PTX might be a potential regimen for treating this subtype of breast cancer.


Venous Thromboembolism Prophylaxis in Inflammatory Bowel Disease: A Two-year Retrospective Study of Patients Presenting With Inflammatory Bowel Disease to a Community Hospital.
Objective We set out to determine the rate of pharmacological venous thromboembolism (VTE) prophylaxis among patients admitted with inflammatory bowel disease (IBD) and indirectly compare it to national trends. We also assessed the demographic and clinical correlates for non-prescription of pharmacologic VTE prophylaxis among IBD patients with and without a flare. Methods We extracted data from 123 patients admitted to our facility with IBD from September 2018 to August 2020 retrospectively. Out of this cohort, 26 patients were excluded and 96 were included in our analysis. Baseline characteristics were analyzed using descriptive statistics. Multiple logistic regression was used to evaluate the correlates of pharmacological VTE prophylaxis use in individuals with IBD and to analyze the predictors of VTE prophylaxis use in patients with IBD flares. Results Out of the 96 patients with IBD included in this study, 61 (63.5%) presented with an IBD flare, and among those with a flare, 26/61 (42.6%) received VTE prophylaxis. IBD patients aged ≥ 65 years and of Black race were less likely to be placed on pharmacological VTE prophylaxis (adjusted odds ratio (AOR) 0.20, 95% CI (0.06 - 0.70), p-value 0.012) and (AOR 0.16, 95% CI (0.05 - 0.50), p-value 0.002) respectively. Among those with a flare, the presence of bright red bleeding per rectum was associated with a low rate of pharmacologic VTE use (AOR 0.01, 95% CI (0.00 -1.78), p-value 0.001). Overall the rate of VTE prophylaxis use in the IBD patient cohort was 56.3% and this was irrespective of flare status. Conclusion Our study showed the low rate of pharmacologic VTE prophylaxis use in IBD patients at this center and this finding was in line with national trends. Interestingly age and the race of patients played a major role in the decision to provide pharmacological VTE prophylaxis but the reason for this finding was not explored by our study. A larger multi-center study is needed to further evaluate these relationships.


Electrochemistry of metal phthalocyanines in organic solvents at variable pressure.
High-pressure electrochemical investigations of representative metallophthalocyanines in solution are reported. The selected systems were ZnPc, CoPc, FePc, and CoTNPc (Pc = phthalocyanine, TNPc = tetraneopentoxyphthalocyanine) in several donor solvents and (for CoTNPc) dichlorobenzene, with [Bu(4)N][ClO(4)] as supporting electrolyte and a conventional Pt electrode referred to Ag(+)(CH(3)CN)/Ag. Electrode reaction volumes deltaV(cell) for CoTNPc and ZnPc show that consecutive ring reductions result in progressive increases in electrostriction of solvent in accordance with Drude-Nernst theory. Reductions of the metal center in CoTNPc and CoPc, however, result in much less negative values of deltaV(cell) than would be expected by analogy with ring reductions of the same charge type. This is attributable to loss of axial ligands following the insertion of antibonding 3d(z)2 electrons on going from Co(III) to low-spin Co(II) and then Co(I). In the same vein, rate constants for reduction of Co(III) centers to Co(II) were an order of magnitude slower than those for other metal center or phthalocyanine ring reductions because of Franck-Condon restrictions. The volumes of activation deltaV(el) were invariably positive for all the electrode reactions and in most cases were roughly equal to the volumes of activation for reactant diffusion deltaV(diff)(), indicating predominant rate control by solvent dynamics rather than by activation in the manner of transition-state theory for which negative deltaV(el) values are expected. For CoTNPc and CoPc in donor solvents, the deltaV(cell) and deltaV(el) data are consistent with the assignments of the successive reduction steps made for CoTNPc in DMF by Nevin et al. (Inorg. Chem. 1987, 26, 570).


Previous experience with behavioral control over stress blocks the behavioral and dorsal raphe nucleus activating effects of later uncontrollable stress: role of the ventral medial prefrontal cortex.
Previous experience with stressors over which the subject has behavioral control blocks the typical behavioral consequences of subsequent exposure to stressors over which the organism has no behavioral control. The present experiments explored the involvement of the ventral medial prefrontal cortex (mPFCv) in mediating this "immunizing" or resilience producing effect of an initial experience with control. Behavioral immunization was blocked by inactivation of the mPFCv with muscimol at the time of the initial experience with control, as well as at the time of the later exposure to uncontrollable stress. Inhibition of protein synthesis within the mPFCv by anisomycin also blocked immunization when administered at the time of the initial controllable stress but had no effect when administered at the time of the later uncontrollable stress. Additional experiments found that the initial experience with control blocks the intense activation of serotonergic cells in the dorsal raphe nucleus that would normally be produced by uncontrollable stress, providing a mechanism for behavioral immunization. Furthermore, mPFCv activity during the initial controllable stressor was required for this effect to occur. These results suggest that the mPFCv is needed both to process information about the controllability of stressors and to utilize such information to regulate responses to subsequent stressors. Moreover, the mPFCv may be a site of storage or plasticity concerning controllability information. These results are consistent with recent research in other domains that explore the functions of the mPFCv.


Reverse Migration, the Black Church and Sexual Health: Implications for Building HIV/AIDS Prevention Capacity in the Deep South.
The Black Church has long been purported as being strongly influential in the lives of Blacks in America. Recent U.S. census data trends highlight a "reverse migration" pattern where Blacks are moving back to the South from larger metropolitan areas in other U.S. geographical regions. This migration pattern parallels the increasing HIV/AIDS prevalence among Blacks in the Deep South. This paper reviews both the historical and current migration patterns among Blacks, as well as the current HIV/AIDS epidemic among Blacks in the Deep South. Thereafter, the authors discuss an existing framework for increasing HIV/AIDS prevention capacity through a conceptual connection of migration, religion and sexual health. The authors use case studies to support the proposed framework. It is hoped that the framework could be used to address HIV/AIDS health disparities and other chronic diseases affecting Blacks in America.


High-affinity binding of bioactive glycosylation-inhibiting factor to antigen-primed T cells and natural killer cells.
High-affinity binding was demonstrated between suppressor-T-cell-derived bioactive glycosylation-inhibiting factor (GIF) and helper T hybridomas and natural killer cell line cells. Inactive GIF present in cytosol of suppressor T cells and Escherichia coli-derived recombinant human GIF (rhGIF) failed to bind to these cells. However, affinity of rhGIF for the target cells was generated by replacement of Cys-57 in the sequence with Ala or of Asn-106 with Ser or binding of 5-thio-2-nitrobenzoic acid to Cys-60 in the molecule. Such mutations and the chemical modification of rhGIF synergistically increased the affinity of GIF molecules for the target cells. The results indicated that receptors on the target cells recognize conformational structures of bioactive GIF. Equilibrium dissociation constant (Kd) of the specific binding between bioactive rGIF derivatives and high-affinity receptors was 10-100 pM. Receptors for bioactive GIF derivatives were detected on Th1 and Th2 T helper clones and natural killer NK1.1(+) cells in normal spleen but not on naive T or B cells. Neither the inactive rGIF nor bioactive rGIF derivatives bound to macrophage and monocyte lines or induced macrophages for tumor necrosis factor alpha production.


Differentiation ability and oncogenic potential of HPV-33- and HPV-33 + ras-transfected keratinocytes.
Five HPV-33-immortalized and 5 HPV-33 + ras-transfected cell lines were characterized in terms of growth in soft agar, tumorigenic potential in nude mice, p21 expression, morphology and expression of differentiation markers in organotypic cultures. No striking differences were observed between the HPV-33-immortalized cell lines and their corresponding ras-transfected counterparts as regards their tumorigenicity in nude mice (only one cell line was able to develop tumors in nude mice) or their behavior on lifted collagen gels. However, all the ras-transfected cell lines gave rise to colonies in soft agar while only 2 HPV-33-transfected lines (CK1 and CK4) displayed this property. The 10 cell lines could be divided into 2 groups with respect to their phenotype in monolayer and in organotypic cultures. Lines from group I (CK2, 3, 5 and their ras-transfected homologous lines) shared a typical epithelial phenotype in monolayer and the ability (a) to form an epithelium similar to a CIN-III lesion and (b) to strongly express keratins K1-K10 and involucrin in organotypic cultures. On the other hand, for the lines from group II (CK1, CK4, CK1EJ7 and CK4EJ5), there was a correlation between an elongated phenotype in monolayer and the property (a) to form a structure similar to a microinvasive carcinoma and (b) to express vimentin and keratins K8-K18. These cell lines, exhibiting various transformation-associated alterations, can be considered as an in vitro model representing various stages of HPV-33-associated cervical carcinogenesis.


Microfluidic origami nano-aptasensor for peanut allergen Ara h1 detection.
In this study, an origami microfluidic electrochemical nano-aptasensor was developed for the rapid detection of the peanut allergen Ara h1. Specifically, the microfluidic aptasensor was fabricated through sequential folding of a piece of chromatography paper substrate patterned with microchannel and screen-printed electrodes. Aptamer-decorated black phosphorus nanosheets (BPNSs) were electrodeposited onto the paper-based electrode surface as sensing probes for enhanced electrochemical detection and high specificity and selectivity. Critical design parameters (the concentration of probe, time for self-assembly of aptamer and reaction time) were investigated to optimize the aptasensor performance. The prepared aptasensor was able to complete detection within 20 min and demonstrated a linear range from 50 ~ 1000 ng/mL with a detection limit of 21.6 ng/mL. The aptasensor was successfully used to detect the Ara h1 spiked cookie dough sample. The proposed method reduces the gap between complex lab testing and food allergen analysis at the point of need.


Exploring the antibacterial and hemolytic activity of shorter- and longer-chain beta-, alpha,beta-, and gamma-peptides, and of beta-peptides from beta2-3-aza- and beta3-2-methylidene-amino acids bearing proteinogenic side chains--a survey.
The antibacterial activities of 31 different beta-, mixed alpha/beta-, and gamma-peptides, as well as of beta-peptides derived from beta2-3-aza- and beta3-2-methylidene-amino acids were assayed against six pathogens (Enterococcus faecalis, Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa), and the results were compared with literature data. The interaction of these peptides with mammalian cells, as modeled by measuring the hemolysis of human erythrocytes, was also investigated. In addition to those peptides designed to fold into amphiphilic helical conformations with positive charges on one face of the helix, one new peptide with hemolytic activity was detected within the sample set. Moreover, it was demonstrated that neither cationic peptides used for membrane translocation (beta3-oligoarginines), nor mixed alpha/beta- or gamma-peptides with somatostatin-mimicking activities display unwanted hemolytic activity.


Canine degenerative myelopathy: a model of human amyotrophic lateral sclerosis.
Canine degenerative myelopathy (CDM) represents a unique naturally occurring animal model for human amyotrophic lateral sclerosis (ALS) because of similar clinical signs, neuropathologic findings, and involvement of the superoxide dismutase 1 (SOD1) mutation. A definitive diagnosis can only be made postmortem through microscopic detection of axonal degeneration, demyelination and astroglial proliferation, which is more severe in the dorsal columns of the thoracic spinal cord and in the dorsal portion of the lateral funiculus. Interestingly, the muscle acetylcholine receptor complexes are intact in CDM prior to functional impairment, thus suggesting that muscle atrophy in CDM does not result from physical denervation. Moreover, since sensory involvement seems to play an important role in CDM progression, a more careful investigation of the sensory pathology in ALS is also warranted. The importance of SOD1 expression remains unclear, while oxidative stress and denatured ubiquinated proteins appear to play a crucial role in the pathogenesis of CDM. In this updated narrative review we performed a systematic search of the published studies on CDM that may shed light on the pathophysiological mechanisms of human ALS. A better understanding of the factors that determine the disease progression in CDM may be beneficial for the development of effective treatments for ALS.


Antimicrobial activity of perilla seed polyphenols against oral pathogenic bacteria.
A perilla seed (Perilla frutescens Britton var. japonica Hara) extract was examined for its antimicrobial activity against oral cariogenic streptococci and periodontopathic Porphyromonas gingivalis. Luteolin, one of the components of perilla seed, showed the strongest antimicrobial effect among the phenolic compounds. According to our results, perilla seed may be the source of an antimicrobial agent that could prevent dental caries and periodontal diseases.


Efficacy and safety of azelastine nasal spray at a dose of 1 spray per nostril twice daily.
Azelastine hydrochloride nasal spray is available worldwide for the treatment of seasonal allergic rhinitis (SAR) and perennial allergic rhinitis. One spray per nostril twice daily is the most commonly recommended dose. To determine the efficacy and safety of azelastine nasal spray, 1 spray per nostril twice daily, in patients with SAR. In 2 studies conducted in the United States we assessed 554 patients with moderate-to-severe SAR who were still symptomatic after a 1-week placebo lead-in period. Patients were randomized to 2 weeks of double-blind treatment with azelastine nasal spray, 1 spray per nostril twice daily, or placebo nasal spray. The primary efficacy variable was change from baseline in total nasal symptom score, consisting of sneezing, itchy nose, runny nose, and nasal congestion. Mean differences in total nasal symptom score between the azelastine and placebo groups were significant in both studies: 2.69 vs 1.31 (P = .01) in study 1 and 3.68 vs 2.50 (P = .02) in study 2. Bitter taste was reported by 8.3% of patients treated with 1 spray per nostril twice daily compared with the labeled incidence of 19.7% with 2 sprays per nostril twice daily. Somnolence was reported by 1 patient (0.4%) using the 1-spray regimen compared with the labeled incidence of 11.5% using the 2-spray regimen. Azelastine nasal spray at a dose of 1 spray per nostril twice daily is effective and has improved tolerability compared with 2 sprays per nostril twice daily in patients with SAR.


Modeling the effects of prl mutations on the Escherichia coli SecY complex.
The apparatus responsible for translocation of proteins across bacterial membranes is the conserved SecY complex, consisting of SecY, SecE, and SecG. Prior genetic analysis provided insight into the mechanisms of protein export, as well as the interactions between the component proteins. In particular, the prl suppressor alleles of secE and secY, which allow export of secretory proteins with defective signal sequences, have proven particularly useful. Here, we report the isolation of novel mutations in secE and secY, as well as the phenotypic effects of combinations of prl mutations. These new alleles, as well as previously characterized prl mutations, were analyzed in light of the recently published crystal structure of the archaeal SecY complex. Our results support and expand a model of Prl suppressor activity that proposes that all of the prlA and prlG alleles either destabilize the closed state of the channel or stabilize the open form. These mutants thus allow channel opening to occur without the triggering event of signal sequence binding that is required in a wild-type complex.


Magnetic core micelles as a nanosorbent for the efficient removal and recovery of three organophosphorus pesticides from fruit juice and environmental water samples.
Sodium dodecyl sulfate coated amino-functionalized magnetic iron oxide nanoparticles were used as an efficient adsorbent for rapid removal and preconcentration of three important organophosphorus pesticides, chlorpyrifos, diazinon and phosalone, by ultrasound-assisted dispersive magnetic solid-phase microextraction. Fabrication of amino-functionalized magnetic nanoparticles was certified by characteristic analyses, including Fourier transform infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy, and transmission electron microscopy. Affecting parameters on the removal efficiency were investigated and optimized through half-fractional factorial design and Doehlert design, respectively. The analysis of analytes was performed by high-performance liquid chromatography with ultraviolet detection. Under the optimum conditions, extraction recoveries for 20 ng/mL of organophosphorus pesticides were in the range of 84-97% with preconcentration factors in the range of 134-155. Replicating the experiment in above condition for five times gave the relative standard deviations <6%. The calibration curves showed high linearity in the range of 0.2-700 ng/mL and the limits of detection were in the range of 0.08-0.13 ng/mL. The proposed method was successfully applied for both removal and trace determination of these three organophosphorus pesticides in environmental water and fruit juice samples.


2D:4D and sexually dimorphic facial characteristics.
The second-to-fourth-digit ratio (2D:4D) may be related to prenatal testosterone and estrogen levels and pubertal face growth. Several studies have recently provided evidence that 2D:4D is associated with other-rated facial masculinity and dominance, but not with facialmetric measures of masculinity. We found that localized face shape differences, shown here to be sexually dimorphic and related to ratings of dominance, were associated with direct and indirect measurements of 2D:4D. In this study we examined various localized features of the face, showing nose width, jaw angle, and lip height to be sexually dimorphic. We then had faces rated for dominance and saw that the most dimorphic characteristics were those most associated with rated dominance, with typically masculine characteristics tending to be associated with high ratings of dominance. Finally, 2D:4D measurements were made using three different techniques. High (feminine) values of 2D:4D were associated with feminine facial characteristics in women, but not in men. It was concluded that certain aspects of facial development are governed by factors that are established prenatally. These aspects may be associated with perceptions of the self by others that are important in the social environment, particularly in terms of intra-sexual competition and mate acquisition.


A primary human macrophage-enteroid co-culture model to investigate mucosal gut physiology and host-pathogen interactions.
Integration of the intestinal epithelium and the mucosal immune system is critical for gut homeostasis. The intestinal epithelium is a functional barrier that secludes luminal content, senses changes in the gut microenvironment, and releases immune regulators that signal underlying immune cells. However, interactions between epithelial and innate immune cells to maintain barrier integrity and prevent infection are complex and poorly understood. We developed and characterized a primary human macrophage-enteroid co-culture model for in-depth studies of epithelial and macrophage interactions. Human intestinal stem cell-derived enteroid monolayers co-cultured with human monocyte-derived macrophages were used to evaluate barrier function, cytokine secretion, and protein expression under basal conditions and following bacterial infection. Macrophages enhanced barrier function and maturity of enteroid monolayers as indicated by increased transepithelial electrical resistance and cell height. Communication between the epithelium and macrophages was demonstrated through morphological changes and cytokine production. Intraepithelial macrophage projections, efficient phagocytosis, and stabilized enteroid barrier function revealed a coordinated response to enterotoxigenic and enteropathogenic E. coli infections. In summary, we have established the first primary human macrophage-enteroid co-culture system, defined conditions that allow for a practical and reproducible culture model, and demonstrated its suitability to study gut physiology and host responses to enteric pathogens.


A survey of croquet injuries.
Of 214 croquet players who responded to a questionnaire, 76 reported at least one injury to hand, wrist or forearm caused by striking the ball. There was no obvious relation to which of the three main grips the player applied to the mallet. Injuries were somewhat more frequent when the mallet shaft consisted of fibreglass than when it was wood, metal or carbon fibre, but a causal relation has not been established. Back injuries seem less troublesome in croquet than in golf.


Effects of combined renin-angiotensin-aldosterone system inhibitor and beta-blocker treatment on outcomes in heart failure with reduced ejection fraction: insights from BIOSTAT-CHF and ASIAN-HF registries.
Angiotensin-converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB) and β-blockers are guideline-recommended first-line therapies in heart failure (HF) with reduced ejection fraction (HFrEF). Previous studies showed that individual drug classes were under-dosed in many parts of Europe and Asia. In this study, we investigated the association of combined up-titration of ACEi/ARBs and β-blockers with all-cause mortality and its combination with hospitalization for HF. A total of 6787 HFrEF patients (mean age 62.6 ± 13.2 years, 77.7% men, mean left ventricular ejection fraction 27.7 ± 7.2%) were enrolled in the prospective multinational European (BIOSTAT-CHF; n = 2100) and Asian (ASIAN-HF; n = 4687) studies. Outcomes were analysed according to achieved percentage of guideline-recommended target doses (GRTD) of combination ACEi/ARB and β-blocker therapy, adjusted for indication bias. Only 14% (n = 981) patients achieved ≥50% GRTD for both ACEi/ARB and β-blocker. The best outcomes were observed in patients who achieved 100% GRTD of both ACEi/ARB and β-blocker [hazard ratio (HR) 0.32, 95% confidence interval (CI) 0.26-0.39 vs. none]. Lower dose of combined therapy was associated with better outcomes than 100% GRTD of either monotherapy. Up-titrating β-blockers was associated with a consistent and greater reduction in hazards of all-cause mortality (HR for 100% GRTD: 0.40, 95% CI 0.25-0.63) than corresponding ACEi/ARB up-titration (HR 0.75, 95% CI 0.53-1.07). This study shows that best outcomes were observed in patients attaining GRTD for both ACEi/ARB and β-blockers, unfortunately this was rarely achieved. Achieving >50% GRTD of both drug classes was associated with better outcome than target dose of monotherapy. Up-titrating β-blockers to target dose was associated with greater mortality reduction than up-titrating ACEi/ARB.


The metabolic syndrome and changing relationship between blood pressure and insulin with age, as observed in Aboriginal and Torres Strait Islander peoples.
To determine the prevalence of the metabolic syndrome (MS) among Aboriginal and Torres Strait Islander peoples. A further objective was to investigate the relationships between fasting insulin and blood pressure (BP) within these groups with increasing age. A cross-sectional population-based study included 369 Torres Strait Islanders (residing in Torres Strait and Far North Queensland), and 675 Aborigines from central Australia. Data necessary for classification of MS was collected, including fasting and 2-h glucose and insulin, urinary albumin and creatinine, anthropometric measurements, BP, serum lipids. The ATPIII criteria classified 43% of Torres Strait Islanders and 44% of Aborigines with MS, whereas 32 and 28%, respectively, had the MS according to WHO criteria. Agreement between the two criteria was only modest (kappa coefficient from 0.28 to 0.57). Factor analyses indicated no cluster including both insulin and BP in either population. Significant correlations (P < 0.05) [adjusted for gender, body mass index (BMI) and waist circumference] were observed between BP and fasting insulin: a positive correlation for Torres Strait Islanders aged 15-29 years, and an inverse correlation for Aborigines aged 40 years and older. Torres Strait Islanders and Aborigines had very high prevalences of the MS. Specific population characteristics (high prevalences of central obesity, dyslipidaemia, renal disease) may make the WHO definition preferable to the ATPIII definition in these population groups. The poor agreement between criteria suggests a more precise definition of the metabolic syndrome that is applicable across populations is required. This study showed an inverse relationship with age for the correlation of BP and fasting insulin.


[Determination of three organotin pesticide residues in apples and cabbages by gas chromatography-electron impact/positive chemical ionization mass spectrometry].
A method for the simultaneous determination of fenbutatin oxide, triphenyltin and cyhexatin in apples and cabbages was developed by gas chromatography-mass spectrometry coupled with two different ionization techniques, electron impact (EI) ionization and positive chemical ionization (PCI). At first, the samples were digested by hydrobromic acid, and extracted by acetone-hexane (1:2, v/v). The extracts were derivatized by sodium tetraethylborate as the derivatization reagent, and cleaned up by the Florisil SPE columns. Finally, the samples were analyzed by GC-EI/MS and GC-PCI/MS in selected ion monitoring (SIM) mode. The results showed that good linearities were obtained with correlation coefficients (r2) greater than 0.997 for fenbutatin oxide in the range of 75-500 μg/L in both foods, triphenyltin in the range of 50-1000 μg/L in cabbages and 50-500 μg/L in apples and cyhexatin in the range of 50-1000 μg/L in the two foods. The accuracy was checked at three spiked levels (50, 100 and 200 μg/kg) in cabbages and apples. The limits of detection (LODs, S/N=3) were 0.01-0.05 mg/kg (EI) and 0.01-0.02 mg/kg (PCI), and the limits of quantifications (LOQs, S/N=10) were 0.03-0.16 mg/kg (EI) and 0.02-0.06 mg/kg (PCI). The average recoveries ranged from 59.24%-97.36% (apples) and 50.54%-94.54% (cabbages) in the mode of EI, and the corresponding values were 65.38%-95.86% and 62.56%-90.44% in the mode of PCI. The relative standard deviations (RSDs) were all less than 6.9% (n=6). The PCI method can be used to improve the accuracy in comparing with the EI, in terms of good selectivity and high sensitivity.


Quantification of left coronary bifurcation angles and plaques by coronary computed tomography angiography for prediction of significant coronary stenosis: A preliminary study with dual-source CT.
To evaluate the diagnostic performance of left coronary bifurcation angles and plaque characteristics for prediction of coronary stenosis by dual-source CT. 106 patients suspected of coronary artery disease undergoing both coronary computed tomography angiography (CCTA) and invasive coronary angiography (CAG) within three months were included. Left coronary bifurcation angles including the angles between the left anterior descending artery and left circumflex artery (LAD-LCx), left main coronary artery and left anterior descending artery (LM-LAD), left main coronary artery and left circumflex artery (LM-LCx) were measured on CT images. CCTA plaque parameters were calculated by plaque analysis software. Coronary stenosis ≥ 50% by CAG was defined as significant. 106 patients with 318 left coronary bifurcation angles and 126 vessels were analyzed. The bifurcation angle of LAD-LCx was significantly larger in left coronary stenosis ≥ 50% than stenosis < 50%, and significantly wider in the non-calcified plaque group than calcified. Multivariable analyses showed the bifurcation angle of LAD-LCx was an independent predictor for significant left coronary stenosis (OR = 1.423, P = 0.002). In ROC curve analysis, LAD-LCx predicted significant left coronary stenosis with a sensitivity of 66.7%, specificity of 78.4%, positive predictive value of 85.2% and negative predictive value of 55.8%. The lipid plaque volume improved the diagnostic performance of CCTA diameter stenosis (AUC: 0.854 vs. 0.900, P = 0.045) in significant coronary stenosis. The bifurcation angle of LAD-LCx could predict significant left coronary stenosis. Wider LAD-LCx is related to non-calcified lesions. Lipid plaque volume could improve the diagnostic performance of CCTA for coronary stenosis prediction.


Search for new lead structures in the isoxazole heterocyclic system.
Looking for active immunosuppressant, a series of substituted phenylamides of 5-aminomethinimino-3-methylisoxazole-4-carboxylic acid was obtained, which showed immunosuppressory activities in the in vitro and in vivo tests, comparable with that of cyclosporine A. Rentgenostructural studies of three most representative derivatives were performed and the molecular modelling of compounds, demonstrating most characteristic biological activities, was performed. In the next stage, quantum-chemical investigations were conducted in order to determine structure-activity relationships.


Current Trends in Sensors Based on Conducting Polymer Nanomaterials.
Conducting polymers represent an important class of functional organic materials for next-generation electronic and optical devices. Advances in nanotechnology allow for the fabrication of various conducting polymer nanomaterials through synthesis methods such as solid-phase template synthesis, molecular template synthesis, and template-free synthesis. Nanostructured conducting polymers featuring high surface area, small dimensions, and unique physical properties have been widely used to build various sensor devices. Many remarkable examples have been reported over the past decade. The enhanced sensitivity of conducting polymer nanomaterials toward various chemical/biological species and external stimuli has made them ideal candidates for incorporation into the design of sensors. However, the selectivity and stability still leave room for improvement.


Status report -- Identifying equity-focussed interventions to promote healthy weights.
We developed screening criteria to identify population health interventions with an equity focus for inclusion on the Public Health Agency of Canada's Canadian Best Practices Portal. We applied them to the area of "healthy weights," specifically, obesity prevention. We conducted a review of the literature and obtained input from expert external reviewers on changes to midstream environments. Interventions had to identify outcomes for groups with an underlying social disadvantage. We included papers with a focus on equity and vulnerable populations, intervention and/or evaluation studies, social determinants of health and healthy weights or obesity prevention. We then appraised the shortlisted studies for quality of evidence to determine eligibility for inclusion as promising practices on the Canadian Best Practices Portal. Few of the references reviewed passed the equity screening criteria (26 out of 2823 published papers reviewed, or 0.9%). Six (of the 26) interventions qualified as promising practices. The ability of the equity screening criteria to distinguish midstream-level interventions for obesity prevention suggests that the criteria have potential to be applied to other public health topics. What is most important about our work is that the Portal, which is no longer being updated but is still accessible, was broadened to include interventions with a focus on equity.


Image Enhancement and Quality Measures for Dietary Assessment Using Mobile Devices.
Measuring accurate dietary intake is considered to be an open research problem in the nutrition and health fields. We are developing a system, known as the mobile device food record (mdFR), to automatically identify and quantify foods and beverages consumed based on analyzing meal images captured with a mobile device. The mdFR makes use of a fiducial marker and other contextual information to calibrate the imaging system so that accurate amounts of food can be estimated from the scene. Food identification is a difficult problem since foods can dramatically vary in appearance. Such variations may arise not only from non-rigid deformations and intra-class variability in shape, texture, color and other visual properties, but also from changes in illumination and viewpoint. To address the color consistency problem, this paper describes illumination quality assessment methods implemented on a mobile device and three post color correction methods.


The Role of Mutuality and Coping in a Nurse-Led Cognitive Behavioral Intervention on Depressive Symptoms Among Dementia Caregivers.
The current study explored whether mutuality and coping predicted and/or mediated the effect of a nurse-led cognitive behavioral intervention (NLCBI) on depressive symptoms of caregivers of persons with dementia. The intervention group (n = 56) received five monthly in-home nurse-led cognitive behavioral sessions and consultation calls after each session. The control group (n = 56) received five monthly short general conversations with the nurse interventionist. Questionnaires on study variables and demographics were collected at baseline, end of intervention, and 2-month follow up. Improved mutuality (β = -0.75, p = 0.049) and active coping (β = -2.06, p = 0.0001) and decreased passive coping (β = 1.43, p = 0.001) were found to predict the reduction of depressive symptoms among caregivers in the NLCBI. However, none of these variables mediated the interventional effect. Regular mental health nursing interventions are suggested to focus on enhancing mutuality and active coping and decreasing passive coping to maintain caregivers' mental health. Caregivers of persons with dementia. Nurse-led cognitive behavioral sessions and subsequent consultation calls. Impacted caregivers' reappraisals, thus improving their active coping skills and mutuality and decreasing their passive coping, which directly reduced their depressive symptoms. Mutuality, active coping, and passive coping played a predicting, but not mediating, role in the effect of the NLCBI. [Res Gerontol Nurs. 2019; 12(1):44-55.].


Identification of Novel and Efficacious Chemical Compounds that Disturb Influenza A Virus Entry in vitro.
Influenza A virus is a negative RNA stranded virus of the family Orthomyxoviridae, and represents a major public health threat, compounding existing disease conditions. Influenza A virus replicates rapidly within its host and the segmented nature of its genome facilitates re-assortment, whereby whole genes are exchanged between influenza virus subtypes during replication. Antiviral medications are important pharmacological tools in influenza virus prophylaxis and therapy. However, the use of currently available antiviral is impeded by sometimes high levels of resistance in circulating virus strains. Here, we identified novel anti-influenza compounds through screening of chemical compounds synthesized de novo on human lung epithelial cells. Computational and experimental screening of extensive and water soluble compounds identified novel influenza virus inhibitors that can reduce influenza virus infection without detectable toxic effects on host cells. Interestingly, the indicated active compounds inhibit viral replication most likely via interaction with cell receptors and disturb influenza virus entry into host cells. Collectively, screening of new synthesis chemical compounds on influenza A virus replication provides a novel and efficacious anti-influenza compounds that can inhibit viral replication via disturbing virus entry and indicates that these compounds are attractive candidates for evaluation as potential anti-influenza drugs.


The efficacy of laparoscopic presacral neurectomy in dysmenorrhea: is it related to the amount of excised neural tissue?
To assess the correlation between the number of excised neural fibers and degree of pain relief following laparoscopic presacral neurectomy (LPSN). In this before and after study, 20 patients with severe midline dysmenorrhea [Visual Analogue Scale (VAS) >80 mm] unresponsive to medical therapy were consecutively enrolled. All patients underwent LPSN. The superior hypogastric plexus was excised and sent for histologic confirmation. Two pathologists counted the number of neural fibers in the surgically removed tissue. VAS was used for pain assessment before and 2nd, 3rd, 6th, and 12th months after the operations. Out of the initial 20 patients undergoing LPSN, eight were excluded from the final analysis due to intraoperative diagnosis of endometriosis; therefore, the remaining 12 patients were evaluated. The pain scores significantly decreased at each follow-up visit compared with the preoperative period (p=0.002). The pathologists, who were blinded, reported the median (minimum-maximum) neural fiber count as 46 (20-85) and 47 (18-83). No significant correlation was demonstrated between the number of excised neural fibers and the amount of pain relief following LPSN. LPSN is an effective surgical procedure to control primary dysmenorrhea. Our preliminary results revealed that the degree of pain relief in cases of severe midline dysmenorrhea was not related to the amount of excised neural tissue in LPSN.


Quantitative analysis of microbicide concentrations in fluids, gels and tissues using confocal Raman spectroscopy.
Topical vaginal anti-HIV microbicides are an important focus in female-based strategies to prevent the sexual transmission of HIV. Understanding microbicide pharmacokinetics is essential to development, characterization and implementation of efficacious microbicide drug delivery formulations. Current methods to measure drug concentrations in tissue (e.g., LC-MS/MS, liquid chromatography coupled with tandem mass spectrometry) are highly sensitive, but destructive and complex. This project explored the use of confocal Raman spectroscopy to detect microbicide drugs and to measure their local concentrations in fluids, drug delivery gels, and tissues. We evaluated three candidate microbicide drugs: tenofovir, Dapivirine and IQP-0528. Measurements were performed in freshly excised porcine buccal tissue specimens, gel vehicles and fluids using two Horiba Raman microscopes, one of which is confocal. Characteristic spectral peak calibrations for each drug were obtained using serial dilutions in the three matrices. These specific Raman bands demonstrated strong linear concentration dependences in the matrices and were characterized with respect to their unique vibrational signatures. At least one specific Raman feature was identified for each drug as a marker band for detection in tissue. Sensitivity of detection was evaluated in the three matrices. A specific peak was also identified for tenofovir diphosphate, the anti-HIV bioactive product of tenofovir after phosphorylation in host cells. Z-scans of drug concentrations vs. depth in excised tissue specimens, incubated under layers of tenofovir solution in a Transwell assay, showed decreasing concentration with depth from the surface into the tissue. Time-dependent concentration profiles were obtained from tissue samples incubated in the Transwell assay, for times ranging 30 minutes - 6 hours. Calibrations and measurements from tissue permeation studies for tenofovir showed good correlation with gold standard LC-MS/MS data. These results demonstrate that confocal Raman spectroscopy holds promise as a tool for practical, minimally invasive, label-free measurement of microbicide drug concentrations in fluids, gels and tissues.


Bridging the Reciprocal Gap between Sleep and Fruit and Vegetable Consumption: A Review of the Evidence, Potential Mechanisms, Implications, and Directions for Future Work.
A substantial burden of disease and mortality globally is attributable to both sleep disruption and low intakes of fruit and vegetable (FV) and there is increasing mechanistic and epidemiological evidence to support a reciprocal relationship between the two. This review provides an overview of experimental and observational studies assessing the relations between sleep and FV consumption from 52 human adult studies. Experimental studies are currently limited and show inconsistent results. Observational studies support a non-linear association with adults sleeping the recommended 7-9 hours/day having the highest intakes of FV. The potential mechanisms linking sleep and FV consumption are highlighted. Disrupted sleep influences FV consumption through homeostatic and non-homeostatic mechanisms. Conversely, FV consumption may influence sleep through polyphenol content via several potential pathways. Few human experimental studies have examined the effects of FV items and their polyphenols on sleep and there is a need for more studies to address this. An appreciation of the relationship between sleep and FV consumption may help optimize sleep and FV consumption and may reduce the burden of chronic diseases. This review provides implications for public health and directions for future work.


Correlation of contrast angiography and histologic pattern with gallium uptake in primary liver-cell carcinoma: noncorrelation with alpha-feto protein. Concise communication.
Seventeen patients with histologically proven primary liver-cell carcinoma were evaluated by a technetium-99m sulfur colloid liver scan as well as with gallium-67 citrate. Twelve of the 17 patients (71%) showed gallium uptake in the tumor. Eleven of the 12 patients (92%) with a moderately or well-differentiated tumor showed increased gallium activity in the abnormality seen on the sulfur colloid scan. The exception in this group was a tumor with a large central area of necrosis. Four of five patients with a poorly differentiated or atypical carcinoma showed absence of gallium activity. Only six of 11 patients with a hypervascular tumor showed a marked increase in gallium uptake. Correlation of gallium with alpha-feto-protein, and with hepatitis antigen A, was poor. We conclude that gallium uptake in primary liver-cell carcinoma will be significant when the tumor shows a moderately to well-differentiated histologic pattern, unless significant necrosis is present. If the blood supply is markedly impaired, gallium uptake is reduced. However, a hypervascular blood supply does not necessarily ensure increased gallium avidity.


Disturbance influences oyster community richness and evenness, but not diversity.
Foundation species in space-limited systems can increase diversity by creating habitat, but they may also reduce diversity by excluding primary space competitors. These contrasting forces of increasing associate diversity and suppressing competitor diversity have rarely been examined experimentally with respect to disturbance. In a benthic marine community in central California, where native oysters are a foundation species, we tested how disturbance influenced overall species richness, evenness, and diversity. Surprisingly, overall diversity did not peak across a disturbance gradient because, as disturbance decreased, decreases in overall species evenness opposed increases in overall species richness. Decreasing disturbance intensity (high oyster abundance) led to increasing species richness of sessile and mobile species combined. This increase was due to the facilitation of secondary sessile and mobile species in the presence of oysters. In contrast, decreasing disturbance intensity and high oyster abundance decreased the evenness of sessile and mobile species. Three factors likely contributed to this decreased evenness: oysters reduced abundances of primary sessile species due to space competition; oysters supported more rare mobile species; and oysters disproportionately increased the relative abundance of a few common mobile species. Our results highlight the need for further studies on how disturbance can differentially affect the evenness and richness of different functional groups, and ultimately how these differences affect the relationship between overall diversity and ecosystem function.


The Relationships between Anabolic Hormones and Body Composition in Middle-Aged and Elderly Men with Prediabetes: A Cross-Sectional Study.
The influence of anabolic hormones and body composition in men with prediabetes (PD) is unknown. In a cross-sectional study we investigated the relationships between total testosterone (TT), calculated free testosterone (cFT), dehydroepiandrosterone sulfate (DHEAS), and insulin-like growth factor 1 (IGF-1) and body composition assessed using dual-energy X-ray absorptiometry (DXA) method in 84 patients with PD (40-80 years) and 56 men in control group. Patients with PD had lower TT, cFT, and DHEAS levels but similar IGF-1 levels in both groups. Patients with PD presented the higher total and abdominal fat as well as the lower total and abdominal lean than control (p < 0.02, p < 0.01, p < 0.05, and p < 0.02, resp.). We observed negative relationship between TT and total fat (p = 0.014) and positive with abdominal lean mass (p = 0.034), while cFT was negatively associated with abdominal (p = 0.02), trunk (p = 0.024), and leg fat (p = 0.037) and positively associated with total (p = 0.022) and trunk lean (p = 0.024). DHEAS were negatively associated with total fat (p = 0.045), and IGF-1 were positively associated with abdominal (p = 0.003) and leg lean (p = 0.015). In conclusion, the lowered anabolic hormones are involved in body composition rearrangement in men with PD. Further studies are needed to establish whether the androgen replacement therapy would be beneficial in men with PD.


Higher frequency of alterations in the p16/CDKN2 gene in squamous cell carcinoma cell lines than in primary tumors of the head and neck.
Sixty-eight primary head and neck squamous cell carcinomas and nine head and neck squamous cell carcinoma cell lines were examined for mutations and homozygous deletions of the p16/CDKN2 gene. Homozygous deletions of the p16/CDKN2 gene were found in three lines, and a mutation was detected in another cell line. In contrast, none of the primary tumors showed homozygous deletions and 11 of 68 tumors had missense or nonsense base changes. Seven tumors contained somatic mutations. Five tumors, including one that also had a somatic mutation, had a probable polymorphism at codon 140 leading to an amino acid change from Ala to Thr. Three of these also contained an apparent polymorphism at codon 98, which did not lead to an amino acid change. The frequency of mutations and deletions detected differs markedly between cell lines (44%) and primary tumors (10%) suggesting that while p16/CDKN2 may play a role in tumorigenesis in some head and neck squamous cell carcinomas, inactivation of p16/CDKN2 probably occurs more frequently in cell lines as a result of adaptation to cell culture.


Encephalitozoon hellem in budgerigars (Melopsittacus undulatus).
Microsporidiosis with concurrent megabacteriosis in budgerigar (Melopsittacus undulatus) chicks contributed to significant economic floss in a commercial pet bird aviary in Mississippi. Three budgerigar chicks, 1-2 weeks old, from the aviary were necropsied. Microscopic lesions in the chicks consisted of heavy infection of enterocytes with microsporidia (2/3; autolysis precluded critical evaluation of the intestine of chick No. 2), multifocal hepatic necrosis and inflammation with intralesional microsporidia (1/3), spherical clusters of microsporidia in the hepatic sinusoids in the absence of inflammation (1/3), and gastric megabacteriosis (3/3). The ultrastructure of the microsporidian spores was consistent with an Encephalitozoon species. The polymerase chain reaction and Southern blot analysis were used to identify the microsporidian as Encephalitozoon hellem, an organism that has only been identified in humans. Encephalitozoon hellem causes keratoconjunctivitis and respiratory infections in humans with acquired immunodeficiency syndrome. This report presents the first confirmed case of microsporidiosis in budgerigars. The finding of E. hellem in pet birds may be important in elucidating the epidemiology of human infections with this organism.


Effects of smoking and smoking cessation on life expectancy in an elderly population in Beijing, China, 1992-2000: an 8-year follow-up study.
We assessed the effects of smoking and smoking cessation on life expectancy and active life expectancy among persons aged 55 years or older in Beijing. This study included 1593 men and 1664 women who participated in the Beijing Longitudinal Study of Aging, which commenced in 1992 and had 4 survey waves up to year 2000. An abridged life table was used to estimate life expectancy, in which age-specific mortality and age-specific disability rates were adjusted by using a discrete-time hazard model to control confounders. The mean ages (SD) for men and women were 70.1 (9.25) and 70.2 (8.72) years, respectively; mortality and disability rates during follow-up were 34.7% and 8.0%, respectively. In both sexes, never smokers had the highest life expectancy and active life expectancy across ages, as compared with current and former smokers. Current heavy smokers had a shorter life expectancy and a shorter active life expectancy than light smokers. Among former smokers, male long-term quitters had a longer life expectancy and longer active life expectancy than short-term quitters, but this was not the case in women. Older adults remain at higher risk of mortality and morbidity from smoking and can expect to live a longer and healthier life after smoking cessation.


A polygenic explanation for Haldane's rule in butterflies.
Two robust rules have been discovered about animal hybrids: Heterogametic hybrids are more unfit (Haldane's rule), and sex chromosomes are disproportionately involved in hybrid incompatibility (the large-X/Z effect). The exact mechanisms causing these rules in female heterogametic taxa such as butterflies are unknown but are suggested by theory to involve dominance on the sex chromosome. We investigate hybrid incompatibilities adhering to both rules in Papilio and Heliconius butterflies and show that dominance theory cannot explain our data. Instead, many defects coincide with unbalanced multilocus introgression between the Z chromosome and all autosomes. Our polygenic explanation predicts both rules because the imbalance is likely greater in heterogametic females, and the proportion of introgressed ancestry is more variable on the Z chromosome. We also show that mapping traits polygenic on a single chromosome in backcrosses can generate spurious large-effect QTLs. This mirage is caused by statistical linkage among polygenes that inflates estimated effect sizes. By controlling for statistical linkage, most incompatibility QTLs in our hybrid crosses are consistent with a polygenic basis. Since the two genera are very distantly related, polygenic hybrid incompatibilities are likely common in butterflies.


A new mechanism of flowering regulation by the competition of isoforms in Osmanthus fragrans.
The regulation of flowering time is typically governed by transcription factors or epigenetic modifications. Transcript isoforms can play important roles in flowering regulation. Recently, transcript isoforms were discovered in the key genes, OfAP1 and OfTFL1, of the flowering regulatory network in Osmanthus fragrans. OfAP1-b generates a full-length isoform of OfAP1-b1 as well as an isoform of OfAP1-b2 that lacks the C-terminal domain. Although OfAP1-b2 does not possess an activation domain, it has a complete K domain that allows it to form heterodimers. OfAP1-b2 competes with OfAP1-b1 by binding with OfAGL24 to create nonfunctional and functional heterodimers. As a result, OfAP1-b1 promotes flowering while OfAP1-b2 delays flowering. OfTFL1 produces two isoforms located in different areas: OfTFL1-1 in the cytoplasm and OfTFL1-2 in the nucleus. When combined with OfFD, OfTFL1-1 does not enter the nucleus to repress the AP1 expression, leading to early flowering. Conversely, when combined with OfFD, OfTFL1-2 enters the nucleus to repress the AP1 expression, resulting in later flowering. Tissue specific expression and functional conservation testing of OfAP1 and OfTFL1 support the new model's effectiveness in regulating flowering. Overall, this study provides new insights into regulating flowering time by the competition of isoforms.


A coral reef benthic system with grazing intensity and immigrated macroalgae in deterministic and stochastic environments.
As the most diverse, productive but vulnerable marine habitats in the world, coral reefs are easily affected by the ubiquitous environmental fluctuations, which could change the population dynamics and induce phase shifts of the ecosystem. In this paper, we consider a coral reef benthic system, where macroalgae, corals and algal turfs compete for the available space on a given region of the seabed with grazing intensity and immigrated macroalgae in both deterministic and stochastic environments. For the deterministic system, we analyze the existence and stability of equilibria, as well as the existence of bifurcations. For the stochastic system, sufficient conditions for the existence of the unique ergodic stationary distribution as well as the extinction of corals are obtained, by choosing suitable Lyapunov functions. Moreover, for the scenario that the system exhibits bistability between a macroalgal-coral coexistence equilibrium and a coral-free equilibrium in the absence of environmental fluctuation, we further investigate the irreversible noise-induced transition from macroalgal-coral coexistence to coral extirpation, and numerically estimate the critical values of noise intensity for the occurrence of such transition with the aids of the technique of stochastic sensitivity functions.


Tolerogenic splenic IDO (+) dendritic cells from the mice treated with induced-Treg cells suppress collagen-induced arthritis.
TGF-β-induced regulatory T cells (iTregs) retain Foxp3 expression and immune-suppressive activity in collagen-induced arthritis (CIA). However, the mechanisms whereby transferred iTregs suppress immune responses, particularly the interplay between iTregs and dendritic cells (DCs) in vivo, remain incompletely understood. In this study, we found that after treatment with iTregs, splenic CD11c(+)DCs, termed "DCiTreg," expressed tolerogenic phenotypes, secreted high levels of IL-10, TGF-β, and IDO, and showed potent immunosuppressive activity in vitro. After reinfusion with DCiTreg, marked antiarthritic activity improved clinical scores and histological end-points were observed. The serological levels of inflammatory cytokines and anti-CII antibodies were low and TGF-β production was high in the DCiTreg-treated group. DCiTreg also induced new iTregs in vivo. Moreover, the inhibitory activity of DCiTreg on CIA was lost following pretreatment with the inhibitor of indoleamine 2,3-dioxygenase (IDO). Collectively, these findings suggest that transferred iTregs could induce tolerogenic characteristics in splenic DCs and these cells could effectively dampen CIA in an IDO-dependent manner. Thus, the potential therapeutic effects of iTregs in CIA are likely maintained through the generation of tolerogenic DCs in vivo.


The Cost-Benefit of Aging: Financial Capability and Well-Being across Age Groups in Brazil.
A large proportion of older persons in developing countries do not have access to pension, which also constrains their ability to afford healthcare services and entails extensive challenges to the well-being of older people. This study aimed to analyze the financial preparedness of different age groups for retirement in Brazil. Data were derived from a survey to empirically validate the proposed relationships between preparedness for retirement and resilience for the future (financial well-being (FWB) outcomes) on the one hand and among demographic and socioeconomic aspects, behaviors and attitudes, knowledge and experience, and "key" psychological factors on the other hand. The sample consisted of 412 individuals aged between 22 and 79 years. FWB was measured using the financial capability and well-being model and regressed on a number of sociodemographic and psychological variables using linear regression analyses. The results demonstrated that preparedness for retirement was strongly related to older age. Additionally, age was correlated with resilience for the future close to zero, which indicates no relationship. Knowledge and the psychological factors of self-control and confidence were positively and strongly related to better financial behavior for all age groups. In addition, grit and resilience for the future were positively related to better financial behavior in the older age group. Furthermore, the variables of retirement contribution were seemingly not viewed as important to the older group compared with their young and mature counterparts. Multidimensional interventions, especially targeting behaviors and psychological patterns, could, therefore, be recommended in advance to young and mature groups to prepare them to secure their old age and achieve FWB.


Outcomes from extensive training in critical care echocardiography: Identifying the optimal number of practice studies required to achieve competency.
Optimal instruction and assessment of critical care ultrasound (CCUS) skills requires an assessment tool to measure learner competency and changes over time. In this study, a previously published tool was used to monitor the development of critical care echocardiography (CCE) competencies, the attainment of performance plateaus, and the extent to which previous experience influenced learning. A group of experts used the Rapid Assessment of Competency in Echocardiography (RACE) scale to rate a large pool of CCE studies performed by novices in a longitudinal design. A total of 380 studies performed by twelve learners were assessed; each study was independently rated by two experts. Learners demonstrated improvement in mean RACE scores over time, with peak performance occurring early in training and a performance plateau thereafter. Learners with little experience received the greatest benefit from training, with an average performance plateau reached at the twentieth study. Supporting earlier results, the RACE scale provided a straightforward means to assess learner performance with minimal requirements for evaluator training. The results of the present study suggest that novices experience the greatest gains in competency during their first twenty practice studies, a threshold which should serve to guide training initiatives.


Australian Neuroscience Society - 30th Annual Meeting and Australian Physiological Society - 50th Anniversary Meeting.
The joint 30th Annual Meeting of the Australian Neuroscience Society and the 50th Anniversary Meeting of the Australian Physiological Society, held in Sydney, included topics covering new developments in the fields of neuroscience and physiology. This conference report highlights selected presentations on potential treatments for neuropathic pain, mood disorders and Alzheimer's disease. Investigational drugs discussed include 4-ACPBPA (Circadian Technologies Ltd/University of Sydney) and F-15599 (Pierre Fabre SA).


Efficacy and Safety of Chuan Huang Fang Combining Reduced Glutathione in Treating Acute Kidney Injury (Grades 1-2) on Chronic Kidney Disease (Stages 2-4): Study Protocol for a Multicenter Randomized Controlled Clinical Trial.
Acute kidney injury (AKI) is a global public health challenge resulting in considerable morbidity and mortality. AKI on chronic kidney disease (CKD) (AKI on CKD, A on C) accounts for about a third of total AKI. For severe AKI grade 3, renal replacement therapy (RRT) should be implemented in time. However, the lack of recognized drug treatment method for AKI grades 1-2 is a crucial problem in clinic. Chuan Huang Fang (CHF) is a Chinese herbal formulation developed for the treatment of A on C from the Shanghai Municipal Hospital of Traditional Chinese Medicine. Our previous studies suggested that CHF might effectively protect renal functions of A on C patients. As a widely used antioxidant in clinic, reduced glutathione (RG) is reported to improve the clinical efficacy of high-flux hemodialysis (HFHD) in severe AKI patients recently. To address the crucial problem mentioned above, thus we design a new clinical protocol of CHF combining RG and try to evaluate the efficacy and safety of this protocol in treating patients diagnosed with CKD stages 2-4 complicated with AKI grades 1-2. This is a multicenter randomized controlled clinical trial. We intend to enroll 162 participants, and these participants will be divided into the RG group, the CHF group, and the RG + CHF group randomly assigning 1 : 1 : 1 principle. The RG group will be general treatments combining RG, the CHF group will be general treatments combining CHF, and the RG + CHF group will be general treatments combining RG and CHF. The duration of treatment will last two weeks. The primary evaluation outcome will be the change in the slope of serum creatinine (Scr) over 2 weeks. Secondary evaluation outcomes include changes in blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), urinary AKI biomarkers (neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), gamma-glutamyl transpeptidase (γ-GT), etc.), traditional Chinese medicine (TCM) symptoms, inflammatory indicators, and oxidative stress indicators. Meanwhile, the vital sign indicators and adverse events (AEs) will be closely observed. These dates will be meticulously recorded and properly handled by investigators throughout the study. Discussion. This study will provide convictive research-derived data to evaluate clinical efficacy and safety of CHF combing RG for CKD stages 2-4 complicated with AKI grades 1-2 and provide an evidence-based recommendation for clinicians. The timely completion of this trial will provide a novel drug treatment method for A on C. This trial is registered with ChiCTR2100043311 and registered on February 9, 2021.


Dynamics of chromatin marks and the role of JMJD3 during pancreatic endocrine cell fate commitment.
Pancreatic endocrine lineages are derived from pancreatic progenitors that undergo a cell fate transition requiring a switch from low to high Ngn3 expression. However, the underlying chromatin regulatory mechanisms are unclear. Here, we performed epigenomic analysis of gene regulatory loci featuring histone marks in cells with low or high level of Ngn3 expression. In combination with transcriptomic analysis, we discovered that in Ngn3-high cells, the removal of H3K27me3 was associated with the activation of key transcription factors and the establishment of primed and active enhancers. Deletion of Jmjd3, a histone demethylase for H3K27me3, at the pancreatic progenitor stage impaired the efficiency of endocrine cell fate transition and thereafter islet formation. Curiously, single-cell RNA-seq revealed that the transcriptome and developmental pathway of Ngn3-high cells were not affected by the deletion of Jmjd3 Our study indicates sequential chromatin events and identifies a crucial role for Jmjd3 in regulating the efficiency of the transition from Ngn3-low to Ngn3-high cells.


Effects of racial density and income incongruity on pregnancy outcomes in less segregated communities.
A previous publication in this journal documented a decreased risk of adverse birth outcomes when African-American women have a positive income incongruity (defined as mothers living in a census tract with a higher household income than would be expected based on their individual education and marital status) and live in a census tract with "predominantly African-American" residents [Pickett, K. E., Collins, J. W. Jr., Masi, C. M., & Wilkinson, R. G. (2005). The effects of racial density and income incongruity on pregnancy outcomes. Social Science & Medicine, 60(10), 2229-2238.]. The communities included in that study were from Chicago and were highly segregated by race. Our objective was to repeat this analysis in a less severely segregated environment: two urban counties (Wake and Durham) in central North Carolina. Rather than assuming an absence of knowledge about the effects of interest, we used the previously published results to inform our prior distributions in a Bayesian logistic regression analysis. This approach, which is analogous to a meta-analysis of the two studies, revealed a protective effect of positive income incongruity for African-American women living in census tracts with high relative African-American density across a much wider range of residential segregation patterns. Positive income incongruity was not associated with a decreased risk of low birth weight or preterm delivery for women living in tracts with a low relative density of African-Americans. These estimates are comparable to those that might have been observed had the original authors included a much more diverse set of communities with respect to degree of segregation, and so these new results provide important information about the generality of this intriguing finding.


Intracellular uptake, retention and cytotoxic effect of adriamycin combined with hyperthermia in vitro.
The intracellular uptake, retention and cytotoxic effect of adriamycin (ADR) were investigated by a flow cytometry technique with NIH 3T3 cells. The intracellular uptake and cytotoxic effect of ADR increased as a function of exposure time and external drug concentration at 37 degrees. A good correlation was found between eventual survival and intracellular ADR uptake. The intracellular uptake and cytotoxic effect of ADR increased with increasing temperature and were shown to be functions of both incubation time and temperature. The intracellular uptake and cytotoxic effect of ADR were increased even at 39 degrees and 41 degrees, temperatures which had no effect on the viability of cells. The combination of hyperthermia (43 degrees) and ADR showed a synergistic effect. It was found that the cytotoxic effects of ADR in combination with various levels of hyperthermia were stronger than those which would be predicted from the intracellular ADR uptake at 37 degrees. The degree of enhancement was temperature-dependent. Since the efflux of intracellular ADR was the same with or without hyperthermia, the increased intracellular ADR uptake caused by elevated temperature was considered to result from an increase in influx.


Phosphonic Acid-Functionalized Polyurethane Dispersions with Improved Adhesion Properties.
A facile route to phosphorus-functionalized polyurethane dispersions (P-PUDs) with improved adhesion properties is presented. (Bis)phosphonic acid moieties serve as adhesion promoting sites that are covalently attached via an end-capping reaction to isocyanate-reactive polyurethane particles under aqueous conditions. The synthetic approach circumvents solubility issues, offers great flexibility in terms of polyurethane composition, and allows for the synthesis of semicrystalline systems with thermomechanical response due to reversible physical cross-linking. Differential scanning calorimetry (DSC) is used to investigate the effect of functionalization on the semicrystallinity. The end-capping conversion was determined via inductively-coupled plasma optical emission spectroscopy (ICP-OES) and was surprisingly found to be almost independent of the stoichiometry of reaction, suggesting an adsorption-dominated process. Particle charge detection (PCD) experiments reveal that a dense surface coverage of phosphonic acid groups can be attained and that, at high functionalization degrees, the phosphonic adhesion moieties are partially dragged inside the colloidal P-PUD particle. Quartz crystal microbalance with dissipation (QCMD) investigations conducted with hydroxyapatite (HAP) and stainless steel sensors as model surfaces show a greatly enhanced affinity of the aqueous P-PUDs and furthermore indicate polymer chain rearrangements and autonomous film formation under wet conditions. Due to their facile synthesis, significantly improved adhesion, and variable film properties, P-PUD systems such as the one described here are believed to be of great interest for multiple applications, e.g., adhesives, paints, anticorrosion, or dentistry.


Mesenchymal stem cell condition medium enhanced cell viability in morphine-treated cells.
Bone marrow mesenchymal stem cells (BM-MSC) have recently been predicted to have a major therapeutic potential due to secretion of soluble factors and the release of cytokines and growth factors, which could mediate the cellular communication to induce cell differentiation/maturity. The aim of the present study was to determine the effect of mBM condition medium on morphine-induced cell death in PC12, U87, AGS and MCF-7 cell lines. The condition media were harvested as mBM soup (mBM soup 24 and mBM soup 48h, respectively). To investigate the effect of mBM soup on cell lines, morphological changes were studied with an inverted microscope, the viability of cells was determined with trypan blue staining and MTT assay, the type of cell death was determined using Hoescht / PI staining, and NO secretion analysis. Viability assay showed that mBM soup (24 and 48 h) in time-dependent manner increased cell viability (pndings suggest that mBM soup can enhance the proliferation and growth of cell lines and can suppress cell death induced by morphine (Fig. 8, Ref. 59). Text in PDF www.elis.sk. Keywords: morphine, BM-MSC soup, cell viability, cell death, NO.


Biochemical outcome of blocking the ergot alkaloid pathway of a grass endophyte.
Neotyphodium sp. Lp1, an endophytic fungus from perennial ryegrass (Lolium perenne), produces the mycotoxin ergovaline in infected grasses, whereas a mutant in which a particular peptide synthetase gene is knocked out does not. We examined the impact of this knockout on other constituents of the ergot alkaloid pathway. Two simple lysergic acid amides, ergine and a previously undescribed amide, were eliminated by the knockout. Lysergic acid accumulated in the knockout endophyte, but quantities were only 13% of the total lysergic acid derivatives accumulated in the wild type. Concentrations of several clavines were not substantially affected. However, a novel clavine accumulated to higher concentrations in perennial ryegrass containing the knockout strain. The results indicate that production of simple lysergic acid amides requires the activity or products of the ergovaline-associated peptide synthetase and that the regulation of ergot alkaloid production is modified in response to the relatively late block in the pathway.


Preventing Prescription Drug Misuse in Work Settings: Efficacy of a Brief Intervention in Health Consciousness.
It is becoming more commonplace for employees to use prescription medication outside of intended use. Opioid and other prescription misuse has implications for the health and productivity of workers. Easy-to-access webinars that help employees learn about alternatives to prescription use may decrease risk. The aim of this study was to examine the efficacy of an interactive but brief health consciousness and prescription drug intervention for a diverse sample of employees and show effectiveness via both Internet-delivered webinar and classroom delivery. Employees from a variety of workplaces filled out pre- and post-questionnaires upon completion of a one-hour long intervention. A total of 114 participants completed the pre- and post-questionnaires. Results showed that, compared with before the training, participants reported significantly more knowledge about prescription drug misuse and alternatives to prescription drug use after the training (t113=7.91, P<.001). Moreover, the medium of presentation (ie, face-to-face vs webinar) did not significantly impact effectiveness of the training (F1,98=1.15, P=.29). In both webinar and classroom formats, participants gained knowledge about alternatives to prescription drug use. This intervention appears to be beneficial to employees and assists in the awareness of prescription drug use in general and in the workplace.


Putative metronidazole neurotoxicosis in a cat.
A presumptive case of metronidazole toxicity in a 3.4-kg adult cat is described. The cat had been treated for suspected inflammatory bowel disease with an anti-inflammatory dose of prednisone and metronidazole (73.5-147 mg/kg PO q24h) for approximately 40 days prior to presentation. Clinical signs were primarily related to the central nervous system, including acute tetraparesis, unresponsiveness, tremors, and vocalization. The patient was euthanatized after 12 days of supportive care. Necropsy revealed no significant macroscopic lesions. Histologic evaluation revealed multifocal, fairly well-demarcated foci of necrosis in the brainstem, extending from the diencephalon to the medulla oblongata. To our knowledge, this is the first report to document histologic lesions associated with metronidazole administration in a cat.


[Case of clear cell hidradenoma with mucinous metaplasia in the forehead--immunohistochemical analysis of the mucin].
Mucinous metaplasia rarely develops in the non-neoplastic skin or its appendages, and almost exclusively confined to the genitalia, palms and soles. Similarly, mucinous metaplasia is quite uncommon in the cutaneous neoplasms and only few cases of clear cell hidradenomas and squamous cell carcinomas with mucinous metaplasia have been reported in the literature. Here we report a new case of clear cell hidradenoma with mucinous metaplasia in the forehead. Our immunohistochemical analysis revealed MUC5AC in the mucinous metaplastic cells of this tumor as in the extramammary Paget's disease, and expression of this gastric foveolar epithelial mucin core protein in these two neoplastic conditions seem to related to their common apocrine origin.


Whole exome sequencing of a single osteosarcoma case--integrative analysis with whole transcriptome RNA-seq data.
Osteosarcoma (OS) is a prevalent primary malignant bone tumour with unknown etiology. These highly metastasizing tumours are among the most frequent causes of cancer-related deaths. Thus, there is an urgent need for different markers, and with our study, we were aiming towards finding novel biomarkers for OS. For that, we analysed the whole exome of the tumorous and non-tumour bone tissue from the same patient with OS applying next-generation sequencing. For data analysis, we used several softwares and combined the exome data with RNA-seq data from our previous study. In the tumour exome, we found wide genomic rearrangements, which should qualify as chromotripsis-we detected almost 3,000 somatic single nucleotide variants (SNVs) and small indels and more than 2,000 copy number variants (CNVs) in different chromosomes. Furthermore, the somatic changes seem to be associated to bone tumours, whereas germline mutations to cancer in general. We confirmed the previous findings that the most significant pathway involved in OS pathogenesis is probably the WNT/β-catenin signalling pathway. Also, the IGF1/IGF2 and IGF1R homodimer signalling and TP53 (including downstream tumour suppressor gene EI24) pathways may have a role. Additionally, the mucin family genes, especially MUC4 and cell cycle controlling gene CDC27 may be considered as potential biomarkers for OS. The genes, in which the mutations were detected, may be considered as targets for finding biomarkers for OS. As the study is based on a single case and only DNA and RNA analysis, further confirmative studies are required.


Brief intervention: reducing the repetition of deliberate self-harm.
Deliberate self-poisoning is one of the commonest reasons for hospital admission in the UK and people who deliberately self-harm are often difficult to engage. Solution-focused brief therapy could help these people as it has the potential to be effective after one session. The liaison psychiatry team at St Luke's Hospital, Middlesbrough, undertook a research project to evaluate the use of SFBT with patients who presented following an act of deliberate self-harm. Of the 40 patients seen only one repeated self-harm within the week of presentation.


Sarcoidosis Illuminations on Living During COVID-19: Patient Experiences of Diagnosis, Management, and Survival Before and During the Pandemic.
Background: Inspired by intense challenges encountered by patients and clinicians, we examined the experiences of living with sarcoidosis in three of the hardest impacted English-speaking cities during the early COVID-19 pandemic: London, New Orleans, and New York. Methods: A multi-disciplinary, multi-national research team including 6 patient leaders conducted qualitative investigations with analyses rooted in grounded theory. Recruitment occurred by self-referral through patient advocacy groups. Results: A total of 28 people living with sarcoidosis participated. The majority of patients had multi-system and severe sarcoidosis. Dominant themes were consistent across groups with differences expressed in spirituality and government and health systems. Racial, gender, and able-bodied inequity were voiced regarding healthcare access and intervention, societal interactions, and COVID-19 exposure and contraction. Agreement regarding extreme disruption in care and communication created concern for disability and survival. Concerns of COVID-19 exposure triggering new sarcoidosis cases or exacerbating established sarcoidosis were expressed. Pre-COVID-19 impediments in sarcoidosis healthcare delivery, medical knowledge, and societal burdens were intensified during the pandemic. Conversely, living with sarcoidosis cultivated personal and operational preparedness for navigating the practicalities and uncertainties of the pandemic. Optimism prevailed that knowledge of sarcoidosis, respiratory, and multi-organ diseases could provide pathways for COVID-19-related therapy and support; however, remorse was expressed regarding pandemic circumstances to draw long-awaited attention to multi-organ system and respiratory conditions. Conclusion: Participants expressed concepts warranting infrastructural and scientific attention. This framework reflects pre- and intra-pandemic voiced needs in sarcoidosis and may be an agent of sensitization and strategy for other serious health conditions. A global query into sarcoidosis will be undertaken.


Controllable Electrical Contact Resistance between Cu and Oriented-Bi2Te3 Film via Interface Tuning.
The contact resistance between metals and semiconductors has become critical for the design of thin-film thermoelectric devices with their continuous miniaturization. Herein, we report a novel interface tuning method to regulate the contact resistance at the Bi2Te3-Cu interface, and three Bi2Te3 films with different oriented microstructures are obtained. The lowest contact resistivity (∼10-7 Ω cm2) is observed between highly (00l) oriented Bi2Te3 and Cu film, nearly an order of magnitude lower than other orientations. This significant decrease of contact resistivity is attributed to the denser film connections, lower lattice misfit, larger effective conducting contact area, and smaller width of the surface depletion region. Meanwhile, our results show that the reduction of contact resistance has little dependence on the interfacial diffusion based on the little change in contact resistivity after the introduction of an effective Ti barrier layer. Our work provides a new idea for the mitigation of contact resistivity in thin-film thermoelectric devices and also gives certain guidance for the size design of the next-level miniaturized devices.


Perception of male-male competition influences Drosophila copulation behaviour even in species where females rarely remate.
Males in many taxa are known to exhibit behavioural plasticity in response to the perceived intensity of sperm competition, reflected in Drosophila melanogaster by increased copulation duration following prior exposure to a rival. We tested the prediction that males do not adjust their copulation effort in response to the presence of a competitor in Drosophila species where there is little or no sperm competition. Contrary to expectations, male plasticity in copulation duration was found in both Drosophila subobscura and Drosophila acanthoptera, species in which females rarely remate. These results are discussed in relation to the adaptive basis of plasticity in these species.


Modulation by Amino Acids: Toward Superior Control in the Synthesis of Zirconium Metal-Organic Frameworks.
The synthesis of zirconium metal-organic frameworks (Zr MOFs) modulated by various amino acids, including l-proline, glycine, and l-phenylalanine, is shown to be a straightforward approach toward functional-group incorporation and particle-size control. High yields in Zr-MOF synthesis are achieved by employing 5 equivalents of the modulator at 120 °C. At lower temperatures, the method provides a series of Zr MOFs with increased particle size, including many suitable for single-crystal X-ray diffraction studies. Furthermore, amino acid modulators can be incorporated at defect sites in Zr MOFs with an amino acid/ligand ratio of up to 1:1, depending on the ligand structure and reaction conditions. The MOFs obtained through amino acid modulation exhibit an improved CO2 -capture capacity relative to nonfunctionalized materials.


Local intimal-medial uptakes of 125I-albumin, 125I-LDL, and parenteral Evans blue dye protein complex along the aortas of normocholesterolemic minipigs as predictors of subsequent hypercholesterolemic atherogenesis.
This report describes the normalized intimal-medial uptakes [uptake (M, mg.cm-2) divided serum concentration (c0, mg.cm-3)] of 125I-albumin, 125I-low-density lipoprotein (LDL), and in vivo Evans blue dye (EBD)-albumin complex as functions of pressure (P), time (t), molecular species (i), and location (z) along a ventral longitudinal z axis of the normal, intact, aortic endothelial surface in adult normocholesterolemic Sinclair Research Farm (SRF) minipigs and compares these uptake (M/c0) measurements with atherogenesis in hypercholesterolemic cohorts. Uptakes of porcine serum 125I-albumin (n = 21) and 125I-LDL (n = 10) were measured in freshly excised, metabolically supported aortas using a recently developed organ-support system. In vivo intimal-medial EBD uptake vs z data were measured photometrically on opened descending aortas from another group (n = 6) of normocholesterolemic, adult, SRF minipigs 18 hours after the intravenous administration of EBD. For comparison purposes, the corresponding incidence of atherosclerotic lesions along the aortic z axis was calculated using topographic data from hypercholesterolemic minipig cohorts (n = 39). The results showed that uptakes varied greatly with t, z, and macromolecule (i) but not with P. More specifically, the value of M/c0 at any location (z) rose with t, was insensitive to P, decreased with macromolecular (i) size, and varied with z in a pattern that "peaked" in the upstream region, decreased to a nadir in the downstream region, and then rose again as it approached the abdominal celiac orifice. The spatially z-averaged uptake rates for the three different labeled serum proteins were 0.31 x 10(-3) cm.h-1 for 125I-albumin, 0.42 x 10(-3) cm.h-1 for EBD-albumin, and 0.04 x 10(-3) cm.h-1 for 125I-LDL. Nondimensionalized analysis of the individual sets of uptake data indicated that the overall uptake relationship [M(t,P,z,i)/c(io), cm] could be characterized empirically by the simple product of two separate functions: one, a "scaling function" [m(z,i)], that described the uptake magnitude for a given i and z and appeared to be independent of t or P; the other, a "shape function" [s(t,P)], that described the shapes of the uptake vs t and P relationships and appeared to be independent of z or i. The "scaling function" [m(z,i)] vs z contour appeared to correlate well with the corresponding atherosclerotic lesion incidence vs z contour from the group of hypercholesterolemic minipig cohorts. Assuming passive transport, it was shown ("Appendix") that m(z,i) can be interpreted physically in terms of an endothelial diffusive permeability coefficient (P,cm.s-1).(ABSTRACT TRUNCATED AT 400 WORDS)


Efficacy and safety profile of fexofenadine HCl: a unique therapeutic option in H1-receptor antagonist treatment.
Results of head-to-head comparative trials suggest that fexo-fenadine might offer distinct advantages compared with other antihistamines. Fexofenadine is highly selective for peripheral H(1)-receptors and does not cross the blood-brain barrier, as shown by positron emission tomography. These data support findings that fexofenadine is nonsedating and does not impair performance or driving ability, even at very high doses. In addition, fexofenadine does not interact with muscarinic receptors, which might offer a potential advantage compared with desloratadine, the recently approved active metabolite of loratadine. Fexofenadine is devoid of adverse cardiac effects, and changes in electrocardiogram parameters are not significantly different from those observed with placebo. Fexofenadine has also been shown to have a favorable effect on nasal congestion. This therapeutic advantage might be related to its significant antiallergic properties, ie, the demonstrated ability of fexofenadine to blunt the inflammatory effects of preformed and de novo synthesized mediators at clinically relevant doses in vivo and in vitro. Cumulatively, these benefits distinguish fexofenadine from other antihistamines and make it an optimum therapeutic option for treating allergy-mediated respiratory and dermatologic diseases.


Human apolipoprotein L1 interferes with mitochondrial function in Saccharomyces cerevisiae.
To the best of our knowledge, the vertebrate apolipoprotein L (APOL) family has not previously been ascribed to any definite pathophysiological function, although the conserved BH3 protein domain suggests a role in programmed cell death or an interference with mitochondrial processes. In the present study, the human APOL1 was expressed in the yeast Saccharomyces cerevisiae in order to determine the molecular action of APOL1. APOL1 inhibited cell proliferation in a non‑fermentable carbon source, such as glycerol, while it had no effect on proliferation in fermentable carbon sources, such as galactose. APOL1, expressed in yeast, is localized in the mitochondrial fraction, as determined via western blotting. APOL1 induced a loss of mitochondrial function, demonstrated by a loss of respiratory index, and mitochondrial membrane potential. Green fluorescent protein tagging of mitochondrial protein revealed that APOL1 was associated with abnormal mitochondrial and lysosomal morphologies, observed by a loss of the normal mitochondrial tubular network. Thus, the results of the present study suggest that APOL1 could be a physiological regulator of mitochondrial function.


[Comparative study of neonatal bacterial meningitis in Lomé, Bobo-Dioulasso, Casablanca and Lyon].
Bacterial meningitis in new-borns remains a serious event because of its high mortality and morbidity rates in Africa. To identify the clinical and bacteriological epidemiology and the outcome of neonatal bacterial meningitis in three African cities. We have analysed and compared three hospital studies done in humid tropical, Sahelian, and desert Africa with a European study. Compared with the European study this African study is characterized by a high mean frequency of neonatal meningitis (6 cases per year against 1.4), more important risk factors linked to pregnancy and childbirth (50% against 33%), high rates of death (61 to 68% against 5%) and sequelae (25 to 40% against 30%), rarity of Streptococcus agalactiae (7 to 15% against 38%) and absence of Listeria. Enterobacteriaceae were predominant both in African (50 to 68%) and European (43%) studies. E. coli appeared as the most frequent germ in both European and African studies and Salmonella as more frequent in Sub-Saharan Africa than in occidental countries. The epidemiological, bacteriological and evolutional aspects of the neonatal meningitis were identical in the three African cities. The African studies were different from the European only by their high incidence, the rarity of S. agalactiae and Listeria and the difficulties of bacterial diagnosis and management, all might explain the high rates of death and sequelae. An epidemiological survey and adequate antimicrobial therapy according to antibiotic susceptibility may improve the outcome.


[False-positive findings of 67-gallium scintigraphy in staging/restaging of malignant lymphoma].
Gallium scintigraphy has been an established method for the diagnosis of malignant lymphomas for some years. If properly interpreted, the value of the method is not necessarily reduced by the lack of tumour specificity and the well known property of 67Ga to accumulate in inflammatory and granulomatous conditions. A retrospective analysis of 123 patients with malignant lymphomas showed false positive 67Ga scintigrams in 7%. These cases demonstrate the spectrum of possible errors. 'False positives' were all those localised areas of uptake which were due to some pathological condition which was not lymphomatous. All the positive gallium findings could be elucidated by clinical, radiological and histological investigations.


The Effect of Adenine Adsorption on Zn (II) Electroreduction in Acetate Buffer.
The paper presents the thermodynamic analysis of adenine adsorption on a mercury electrode in an acetate buffer at pH 3 and pH 4. Adsorption energy and constants were determined using the Frumkin isotherm and the virial isotherm. Stronger adsorption in the buffer at pH 3 was observed in comparison to the buffer at pH 4. Using cyclic voltammetry and Faraday impedance measurement, an inhibitory effect of adenine on the kinetics of Zn (II) ion electro-reduction was observed.


Treatment of haemorrhoids by rubber band ligation.
Outpatient treatment of haemorrhoids by elastic band ligation without anaesthetic was performed in 75 patients. Clinical review showed that 65 returned to work within 24 h of ligation, 8 in 48 h and 2 after 48 h. No patient required hospitalisation for either rectal bleeding or pain after ligation. In the first week after treatment 36 were completely symptom-free, 26 had minimal discomfort and 13 had moderate pain with a sense of imcomplete evacuation in the rectum, and some frequency of call to stool lasting up to 7 days in 1. Follow-up at 8-26 months (mean 10 months) showed that 59 were symptom free, only occasional rectal bleeding occurred in 7 and more frequent irregular bleeding in 2. Religation of residual haemorrhoids was performed in 7 and 2 and a haemorrhoidectomy. For the majority of patients hospitalisation and loss of work were avoided.


RNA Signaling in Pulmonary Arterial Hypertension-A Double-Stranded Sword.
Recognition of and response to pathogens and tissue injury is driven by the innate immune system via activation of pattern recognition receptors. One of the many patterns recognized is RNA and, while several receptors bind RNA, Toll-like receptor 3 (TLR3) is well placed for initial recognition of RNA molecules due to its localization within the endosome. There is a growing body of work describing a role for TLR3 in maintenance of vascular homeostasis. For example, TLR3 deficiency has been shown to play repair and remodeling roles in the systemic vasculature and in lung parenchyma. A hallmark of pulmonary arterial hypertension (PAH) is pulmonary vascular remodeling, yet drivers and triggers of this remodeling remain incompletely understood. Based on its role in the systemic vasculature, our group discovered reduced endothelial TLR3 expression in PAH and revealed a protective role for a TLR3 agonist in rodent models of pulmonary hypertension. This review will provide an overview of RNA signaling in the vasculature and how it relates to PAH pathobiology, including whether targeting double-stranded RNA signaling is a potential treatment option for PAH.