DNA damage and repair in atherosclerosis: current insights and future perspectives.
Atherosclerosis is the leading cause of morbidity and mortality among Western populations. Over the past two decades, considerable evidence has supported a crucial role for DNA damage in the development and progression of atherosclerosis. These findings support the concept that the prolonged exposure to risk factors (e.g., dyslipidemia, smoking and diabetes mellitus) leading to reactive oxygen species are major stimuli for DNA damage within the plaque. Genomic instability at the cellular level can directly affect vascular function, leading to cell cycle arrest, apoptosis and premature vascular senescence. The purpose of this paper is to review current knowledge on the role of DNA damage and DNA repair systems in atherosclerosis, as well as to discuss the cellular response to DNA damage in order to shed light on possible strategies for prevention and treatment.


In vitro anti-cataract evaluation of standardised Abies pindrow leaf extract using isolated goat lenses.
Oxidative stress is known to spark off the pathogenesis of cataract. Antioxidant potential of Abies pindrow Royle leaf extract (APE) is well established in the literature. In this context, standard aqueous leaf extract of this plant was evaluated for its role in hydrogen peroxide-induced cataract in isolated goat lenses using varying concentrations (5, 10, 15 and 20 mg/mL). Total phenol and flavonoidal content was evaluated and found to be high in concentration. Biochemical parameters, namely superoxide dismutase (SOD), glutathione (GSH), total protein content (TPC) and malondialdehyde (MDA), were evaluated. SOD, GSH and TPC formation was found to increase proportionally with increasing concentration. However, MDA level decreased significantly as the concentration of the extract increased. The results suggest that the extract under investigation can delay the onset and/or prevent the progression of cataract. Its anti-cataract potential may be attributed to the presence of high phenolics and flavonoids in APE. Photographic evaluation, further, confirmed the observation.


Trypanosoma cruzi seroprevalence among solid organ donors in Ceará State, Brazil.
The transmission of Chagas disease (CD) through blood transfusion, organ transplantation, and oral transmission has gained greater visibility as a result of intensified vector control activities in endemic regions and to control CD in non-endemic regions. In Brazil, Ceará is one of the states that perform the most organ transplants. Therefore, the objective of this study was to assess the prevalence of Trypanosoma cruzi infection in organ donor candidates. A retrospective analysis was performed on data from potential organ donors at the Center of Transplantation of the State of Ceará from 2010 - 2015. Data from a total of 2,822 potential donors were obtained, of which 1,038 were effective donors and 1,784 were excluded, likely due to lack of family authorization or medical contraindication. The prevalence of T. cruzi infection among these potential donors was 1.3% (n = 29). The majority of infected donors were males aged 41 - 60 years, residing in the interior of the state. Interestingly, 72.4% (n = 21) had positive or inconclusive serology for additional infections, such as cytomegalovirus, hepatitis B and C, and toxoplasmosis. Probability analysis revealed that stroke was the most common cause of death among potential donors with CD. There was a high prevalence of CD and other coinfections among potential solid organ donors in Ceará, and statistical tests have shown that these individuals are at increased risk of stroke when compared to potential non-reactive donors. This work highlights the importance of screening DC infection in potential donors.


Variables discriminating between cryptogenic glomerular lesions in adults with the nephrotic syndrome.
A univariate analysis of individual clinical and biochemical values of adult patients with cryptogenic nephrotic syndrome has shown that significant differences exist between patients with proliferative glomerulonephritis, 'minimal change' nephritis and membranous nephropathy. For any given adult patient with the condition, the most likely clinical diagnosis is proliferative disease and the next, minimal change. These two diagnoses together account for most cases. The best clinical discriminants between them are the systolic blood pressure and plasma cholesterol concentration. If the systolic pressure is greater than 145 mm Hg proliferative disease is more likely, but if the cholesterol is greater than 530 mgm/100ml, a minimal change lesion is more likely. A scattergram for combining these variables in clinical practice is given, showing a zone of uncertainty where renal biopsy would be indicated. Although single variables do not permit discrimination between membranous nephropathy and the other two groups, it is suggested that analytical techniques where combinations of variables are used may be helpful, and should be developed.


Fatty acid metabolism changes in association with neurobehavioral deficits in animal models of fetal alcohol spectrum disorders.
Fetal alcohol spectrum disorders (FASD) show behavioral problems due to prenatal alcohol exposure (PAE). A previous study reports changes in gene expressions linked to fatty acid (FA) metabolism in the cerebral cortex of the PAE mouse model. We find an increase of palmitic acid and arachidonic acid in phospholipid in the cerebral cortex of PAE at postnatal day 30. The increase of palmitic acid is consistent with increase of the producing enzyme, Fasn (fatty acid synthase). Decrease of 26:6 FA is also consistent with the increase of the enzyme which uses 26:6 as a substrate for making very long chain FAs, Elovl4 (elongation of very long chain fatty acids protein 4). However, there is no increase in the elongated products. Rather, lipid droplets (LDs) accumulated in the brain. Although FA-associated metabolic measurements are not affected by PAE, the abundance of FA-related gut microbiota is altered. This suggests that the gut microbiome could serve as a tool to facilitate uncovering the brain pathophysiology of FASD and a potential target to mitigate neurobehavioral problems.


Evaluation of Columbia, USMARC-Composite, Suffolk, and Texel rams as terminal sires in an extensive rangeland production system: I. Ewe productivity and crossbred lamb survival and preweaning growth.
A 3-yr study was conducted to comprehensively evaluate Columbia, Suffolk, USMARC-Composite (Composite), and Texel breeds as terminal sires in an extensive rangeland production system. The objective was to estimate breed-of-ram effects on ewe fertility, prolificacy, and dystocia, and sire breed effects on lamb survival and growth until weaning at approximately 132 d of age. Data were from 22 Columbia, 22 Composite, 21 Suffolk, and 17 Texel rams with 957 exposures to 574 adult Rambouillet ewes (3- to 7-yr-old at lambing), 908 lambings, and 1,834 lambs. Ram breed did not affect ewe fertility (mean = 94.9%; p = 0.73), total number born per ewe lambing (mean = 2.02 lambs; p = 0.20), number born alive per ewe lambing (mean = 1.90 lambs; p = 0.24), or number weaned per ewe lambing (mean = 1.45 lambs, p = 0.94). Dystocia rates were different (p = 0.01) for ewes mated to Columbia (12.2%), Composite (13.5%), Suffolk (25.7%), and Texel rams (31.9%) during 1 yr of the study, but differences among ram breeds were not repeatable (p ≥ 0.38) during the other 2 yr. Suffolk-sired lambs were heavier (p ≥ 0.02) at birth (5.5 kg) and weaning (40.3 kg) than lambs sired by the other breeds, which did not differ (p ≥ 0.34) for birth weight (mean = 5.3 kg). Texel-sired lambs (37.4 kg) were lighter (p ≥ 0.02) at weaning than Columbia- (38.8 kg) and Composite-sired (38.4 kg) lambs, which did not differ (p = 0.40) for weaning weight. Sire breed effect approached significance (p = 0.06) for lamb survival to weaning; estimated survival probabilities were 0.87 (Columbia), 0.89 (Composite), 0.93 (Suffolk), and 0.86 (Texel) for lambs reared by their birth dam. Interaction between sire breeds and birth weight affected (p < 0.001) lamb survival and revealed that lightweight Columbia- and Suffolk-sired lambs had a greater risk of death than lightweight lambs sired by Composite and Texel rams, but risk of death did not increase substantially for heavyweight lambs from any of the breeds. When mated to adult Rambouillet ewes in an extensive rangeland production system, the use of Suffolk rams is warranted to improve preweaning growth of market lambs and is not predicted to affect ewe fertility, ewe prolificacy, dystocia, or lamb survival compared with the other sire breeds we tested.


Lipopolysaccharides of Legionella erythra and Legionella oakridgensis.
The chemical composition of lipopolysaccharides from Legionella erythra and Legionella oakridgensis was analysed. Sodium dodecyl sulfate polyacrylamide gel electrophoresis showed both lipopolysaccharides to have a smooth-type character. The polysaccharide part of both lipopolysaccharides contained D-mannose, D-glucose, D-glycero-D-mannoheptose, L-glycero-D-manno-heptose, 2-keto-3-deoxyoctonic acid, L-fucosamine, D-glucosamine, and glucosamine phosphate. In addition, L-rhamnose, glycerol phosphate, and glucose phosphate were identified in the polysaccharide part of L. erythra lipopolysaccharide. The main sugar identified in the lipid A part of both lipopolysaccharides, 2,3-diamino-2,3-dideoxy-D-glucose, was found to be substituted with a complex fatty acid composition including at least 16 different amide-linked 3-hydroxy fatty acids. Both lipopolysaccharides contained nonhydroxy fatty acids and the uncommon 27-oxo-octacosanoic acid, 29-oxotriacontanoic acid, and 27-hydroxyoctacosanoic acid. The lipopolysaccharide of L. oakridgensis also contained 29-hydroxytriacontanoic acid. The dioic long-chain acids heptacosane-1,27-dioic acid and nonacosane-1,29-dioic acid were only present in the lipopolysaccharide of L. erythra.


Synergistic Amination of Graphene: Molecular Dynamics and Thermodynamics.
Functionalization of graphene using organic moieties constitutes an affordable way to modulate its physical and chemical properties. Finding an exact structural formula of functionalized graphene using experimental approaches is challenging. We studied in detail the thermal stability and thermodynamics of amino- and ethylamino-graphene and found a surprising synergistic effect: more amino groups stabilize functionalized graphene favoring further amination, whereas a small concentration of amino groups is unstable in many cases. The functional groups can be attached either on the same side or simultaneously on different sides of the graphene sheet. Deformation of functionalized graphene is proportional to the number of amino groups. Complete amination leading to formation of the ultimate product, Cx(NH2)x, is hindered sterically. Our study assists in the determination of the structure of chemically modified graphene and makes specific predictions that can be tested and validated experimentally.


Improved adenoma detection with Endocuff Vision: the ADENOMA randomised controlled trial.
Low adenoma detection rates (ADR) are linked to increased postcolonoscopy colorectal cancer rates and reduced cancer survival. Devices to enhance mucosal visualisation such as Endocuff Vision (EV) may improve ADR. This multicentre randomised controlled trial compared ADR between EV-assisted colonoscopy (EAC) and standard colonoscopy (SC). Patients referred because of symptoms, surveillance or following a positive faecal occult blood test (FOBt) as part of the Bowel Cancer Screening Programme were recruited from seven hospitals. ADR, mean adenomas per procedure, size and location of adenomas, sessile serrated polyps, EV removal rate, caecal intubation rate, procedural time, patient experience, effect of EV on workload and adverse events were measured. 1772 patients (57% male, mean age 62 years) were recruited over 16 months with 45% recruited through screening. EAC increased ADR globally from 36.2% to 40.9% (P=0.02). The increase was driven by a 10.8% increase in FOBt-positive screening patients (50.9% SC vs 61.7% EAC, P<0.001). EV patients had higher detection of mean adenomas per procedure, sessile serrated polyps, left-sided, diminutive, small adenomas and cancers (cancer 4.1% vs 2.3%, P=0.02). EV removal rate was 4.1%. Median intubation was a minute quicker with EAC (P=0.001), with no difference in caecal intubation rate or withdrawal time. EAC was well tolerated but caused a minor increase in discomfort on anal intubation in patients undergoing colonoscopy with no or minimal sedation. There were no significant EV adverse events. EV significantly improved ADR in bowel cancer screening patients and should be used to improve colonoscopic detection. NCT02552017, Results; ISRCTN11821044, Results.


k-space theory and convective gains of stimulated Raman side scattering.
We have developed a k-space theory for stimulated Raman scattering. The theory is used to calculate the convective gain of stimulated Raman side scattering (SRSS) in order to clarify the discrepancies found between previous gain formulas proposed in the literature. The gains are dramatically modified by the eigenvalue of SRSS, and the maximum gain occurs not at the perfect wave-number matching condition but instead at a wave number having a small deviation that is associated with the eigenvalue. Numerical solutions of the k-space theory equations are compared with, and used to verify, analytically derived gains. We demonstrate connections to the existing path integral theories, and we derive a similar path integral formula in k space.


Infections of the heart complicating acute myocardial infarction.
Purulent pericarditis is a serious but uncommon disorder which rarely complicates acute myocardial infarction. We have described a patient who had fatal purulent pericarditis subsequent to Swan-Ganz catheterization, which was done to facilitate the management of left ventricular failure complicating acute myocardial infarction. Although rare, purulent pericarditis should be considered in the differential diagnosis of otherwise unexplained sepsis associated with myocardial infarction. The presence of a pericardial effusion may rapidly be confirmed by echocardiography, and diagnostic pericardiocentesis undertaken.


Voiding cystourethrography as a predictor of reflux nephropathy in children with urinary-tract infection.
Most children who develop renal damage (scarring) after urinary-tract infection have vesicoureteral reflux. Voiding cystourethrography is therefore usually recommended as the initial radiologic study in children with urinary-tract infection. However, renal damage may occur also in the absence of reflux. The aim of this investigation was to determine the sensitivity and predictive value of reflux during voiding cystourethrography in identifying children at risk for renal damage. Eighty-four consecutive children, 2 months to 6 years old, with nonobstructive, first-known, febrile urinary-tract infection underwent voiding cystourethrography and urography. Twenty-seven (32%) had reflux and 10 (12%) had or developed renal damage. Two of the children and four of the kidneys with renal damage had no reflux at initial examination. The sensitivity of reflux as a marker for renal damage was 80%, specificity was 74%, positive predictive value was 30%, and negative predictive value was 96%. Thus, most children who develop renal damage after urinary-tract infection have reflux during voiding cystourethrography. However, there is a risk, albeit small, for renal damage to occur in the absence of reflux.


Overexpression of BSK5 in Arabidopsis thaliana Provides Enhanced Disease Resistance.
Plant surface-localized pattern recognition receptors (PRRs) recognize pathogen- or damage-associated molecular patterns (PAMP/DAMPs) and activate pattern-triggered immunity (PTI). PRRs recruit receptor-like cytoplasmic kinases (RLCKs) to transduce the perceived signal to downstream signaling components. Brassinosteroid-signaling kinase 5 (BSK5) is a member of the RLCK XII subfamily and mutational analysis revealed its involvement in plant immunity. Here, we provide evidence that overexpression of BSK5 in transgenic Arabidopsis plants enhanced disease resistance to the bacterial pathogen Pseudomonas syringae and to the fungus Botrytis cinerea. Remarkably, upon treatment with the flg22, elf18 and pep1 PAMP/DAMPs, BSK5-overexpressing plants displayed higher levels of immune responses, including production of reactive oxygen species, callose deposition at the cell wall, and PATHOGENESIS-RELATED1 (PR1) gene expression. Together, these findings further substantiate the role of BSK5 in plant immunity and illustrate its potential use for improving plant disease resistance.


Polyglutamine expansion affects huntingtin conformation in multiple Huntington's disease models.
Conformational changes in disease-associated or mutant proteins represent a key pathological aspect of Huntington's disease (HD) and other protein misfolding diseases. Using immunoassays and biophysical approaches, we and others have recently reported that polyglutamine expansion in purified or recombinantly expressed huntingtin (HTT) proteins affects their conformational properties in a manner dependent on both polyglutamine repeat length and temperature but independent of HTT protein fragment length. These findings are consistent with the HD mutation affecting structural aspects of the amino-terminal region of the protein, and support the concept that modulating mutant HTT conformation might provide novel therapeutic and diagnostic opportunities. We now report that the same conformational TR-FRET based immunoassay detects polyglutamine- and temperature-dependent changes on the endogenously expressed HTT protein in peripheral tissues and post-mortem HD brain tissue, as well as in tissues from HD animal models. We also find that these temperature- and polyglutamine-dependent conformational changes are sensitive to bona-fide phosphorylation on S13 and S16 within the N17 domain of HTT. These findings provide key clinical and preclinical relevance to the conformational immunoassay, and provide supportive evidence for its application in the development of therapeutics aimed at correcting the conformation of polyglutamine-expanded proteins as well as the pharmacodynamics readouts to monitor their efficacy in preclinical models and in HD patients.


The effects of same-session combined exercise training on cardiorespiratory and functional fitness in older adults: a systematic review and meta-analysis.
Endurance and strength training are effective strategies for counteracting age-associated reductions in physical performance in older adults, with a combination of both exercise modes recommended to maximise potential fitness benefits. This meta-analysis sought to quantify the effects of same-session combined endurance and strength training on fitness in adults aged over 50 years. Five electronic databases were searched with studies required to include one of the following outcome measures: VO2peak, 6-min walk test (6MWT), 8-ft timed up-and-go (TUG), and 30-s chair stand. Separate random-effects meta-analyses compared combined training with (1) no-exercise control, (2) endurance training, and (3) strength training with probabilistic magnitude-based inferences subsequently applied. Twenty-seven studies involving 1346 subjects with a mean age of 68.8 years (range 54-85 years) were included in the analysis. The meta-analysed effect on VO2peak was a moderately beneficial effect for the combined training compared to no-exercise controls (3.6 mL kg-1 min-1; ± 95% confidence limits 0.8 mL kg-1 min-1) with additional increases for studies with greater proportions of female participants and shorter training interventions. Combined training also had small-to-moderately beneficial effects on VO2peak when compared to endurance training (0.8 mL kg-1 min-1; ± 1.0 mL kg-1 min-1), 30-s chair stand when compared with strength training (1.1 repetitions; ± 0.5 repetitions) and on TUG (0.8 s; ± 0.7 s), 30-s chair stand (2.8 repetitions; ± 1.7 repetitions), and 6MWT (31.5 m; ± 22.4 m) when compared to no-exercise controls. All other comparisons were unclear. Same-session combined training can induce clinically relevant fitness improvements in older adults.


Spontaneous regression of lipomyelomeningocele associated with terminal syringomyelia in a child. Case report.
The authors present the case of a 3-month-old girl who presented with lipomyelomeningocele (LMM) associated with a low-lying conus and a terminal syrinx. At the time of presentation, the girl had a mild neurological, but congenital, deficit: weakness of the right foot and calf as well as absence of the right ankle reflex. Bladder assessment was normal, and it was decided to monitor this child closely, without performing surgery. Results of further magnetic resonance imaging performed 1 year after diagnosis and when the girl was 28 months old, showed a significant regression of LMM and associated syrinx. Interestingly, the child remained neurologically unchanged. Although described in the literature, spontaneous regression of LMM is a very unusual situation, and very few cases have been reported. This case represents the first report of concomitant regression of an associated syrinx. Close follow-up of nonsurgically treated children is mandatory, as the risk of late deterioration remains.


[Nervous system tumour proteins. G.F.A. and hyaluronectin (author's transl)].
G.F.A. (gliofibrillary acid protein) and hyaluronectin studied here are two antigens defined by the heteroantibodies which appear in the serum of the immunised animal. G.F.A. is associated with gliofilaments and is considered as an astrocyte marker, either normal or tumoral. Hyaluronectin, is found in the Ranvier nodes and at the periphery of neurones. It is not specific to the nervous system. It is found in all tissues and tumors, and in particular marks the intercellular spaces of gliomas, where it is associated with hyaluronic acid for which it has a great affinity. Serum estimation of these Proteins is being undertaken with the view to a clinical application.


Vickers micro-hardness study of the effect of fluoride mouthwash on two types of CAD/CAM ceramic materials erosion.
The aim of this study was to evaluate the protective effects of fluoride mouthwash on the surface micro-hardness of two types of CAD/CAM ceramics after exposure to acidic solutions. 40 samples (5 × 5 × 3 mm3) were prepared from two different ceramics: Vitabloc Mark II CAD, and IPS e.max CAD. The samples were randomly divided into 5 groups in each ceramic (n = 8) immersed in different solutions: Gs: saliva: GGA: gastric acid, GAA: acetic acid, GFGA: sodium fluoride + gastric acid, GFAA: sodium fluoride + acetic acid. The microhardness of samples was measured before and after immersion in different solutions by Vickers microhardness tester. By subtracting the microhardness values after and before immersion, the microhardness changes of the samples were obtained. Data were analyzed by Two-way analysis of variance, one-way analysis of variance, and Tukey test (α = 0.05). Immersion in different solutions reduced the microhardness. Microhardness loss was significantly affected in G FAA and G FGA groups in both types of ceramics (P < 0.05). For Vitabloc Mark II groups, the microhardness loss was significantly higher in GFAA and GFGA compared to IPS e.max CAD P < 0.001). Fluoride mouthwash in conjunction with acidic solutions may adversely affect microhardness of Vitabloc Mark II CAD, and IPS e.max CAD that may consequently compromise the clinical service. Vitabloc Mark II CAD was significantly more affected than IPS e.max CAD.


Chikungunya virus isolation using simplified cell culture technique in Mauritius.
During the chikungunya outbreak of 2005 - 2006, the only laboratory facilities available in Mauritius were virus isolation in cell culture tubes and serology. The laboratory was submerged with large numbers of blood samples. Comparative isolation was made in human embryonic lung (HEL) and VERO cells grown in 96-well plate. Culture on HEL cells was found to be more sensitive and presence of cytopathic effect (CPE) was observed earlier than in VERO cells. Out of the 18 300 blood samples inoculated on HEL, 11 165 were positive. This virus isolation method was of great help for the surveillance and control of the vectors. In cases of an outbreak a cheap, rapid and simple method of isolating chikungunya virus is described.


Accuracy of a random-walk-based approach in the determination of equilibrium bond lengths and harmonic frequencies for some doublet first-row diatomic radicals.
The accuracy of equilibrium bond lengths and harmonic frequencies for 12 doublet first-row diatomic radicals is presented as predicted by the fixed-node diffusion quantum Monte Carlo method based on the Ornstein-Uhlenbeck random walk guided by the floating spherical Gaussian orbital and spherical Gaussian geminal-type trial wave function. Compared to the experimental determined values, the random-walk-based approach gives the absolute mean deviations of 0.0019 A and 18 cm-1 for the equilibrium bond length and harmonic frequency, respectively. We also compare the random-walk-based results with some coupled-cluster-based values.


Vitexin inhibits Aβ25-35 induced toxicity in Neuro-2a cells by augmenting Nrf-2/HO-1 dependent antioxidant pathway and regulating lipid homeostasis by the activation of LXR-α.
Amyloid beta (Aβ) formation is one of the neuropathological hallmarks of Alzheimer's disease (AD), which induces the generation of reactive oxygen species (ROS), further leading to the alteration of several signalling pathways. In the present study, vitexin has been evaluated for its neuroprotective activity against Aβ25-35 induced toxicity in Neuro-2a cells. Results of cell free studies indicated that vitexin significantly inhibited the aggregation of Aβ25-35. Studies in Neuro-2a cells revealed that Aβ25-35 significantly affected the cell viability by inducing ROS mediated toxicity and apoptosis. However, pre-treatment of Neuro-2a cells with vitexin (50 μM) significantly restored the cell viability up to 92.86 ± 5.57%. Vitexin has been found to inhibit the production of free radicals and suppress ROS mediated lipid peroxidation, protein oxidation and loss of membrane potential. Also, vitexin modulated the expression of genes involved in antioxidant response mechanisms (Nrf-2, HO-1), cholesterol metabolism (LXR-α, APOE, ABCA-1, Seladin-1), and endoplasmic reticulum stress (Grp78, Gadd153) to offer neuroprotection. Aβ25-35 induced caspase-3 activation, and Bax protein expression was also found to be significantly inhibited by vitexin. Taken together, our results indicate that vitexin offers neuroprotection to cells in part via augmenting the antioxidant mechanisms, maintaining lipid homeostasis and inhibiting apoptosis induced by Aβ.


Hemodynamic, adjusted treatment of hypertension in pregnancy. - Part I: Infusionary osmo-oncotherapy.
In hypertension pregnancy a hypoperfusion syndrome of the peripheral tissues, caused by disturbances of the microcirculation, first of all endangers the fetus in utero. The aim of treatment is to correct the hypertension in such a way that perfusion of the uteroplacental unit, as one important part of the total peripheral resistance, increases. We investigated the cardiovascular effects of intravenous infusions of 10% mannitol, 40% sorbitol, 10% low molecular dextran, 10% low molecular dextran with an admixture of 10% mannitol, as well as of the successive application of 40% sorbitol and 10% low molecular dextran in hypertensive late pregnant patients. The specific effects of osmotherapy, oncotherapy, and osmo-oncotherapy are described in detail. In severe cases requiring acute treatment, the osmo-oncotherapy is the most advantageous because it combines raising cardiac output, decreasing total peripheral resistance, and edema-mobilizing and diuresis-inducing effects.


Converting enzyme inhibitors and the interaction between kinins and eicosanoids.
Inhibitors of the angiotensin-converting enzyme (ACE = kininase II) by definition have a dual action: prevention of angiotensin II generation and inhibition of kinin degradation. Although the first mechanism is generally accepted, it may not by itself be sufficient to explain the acute blood pressure-lowering action of these compounds. Studies in experimental and clinical hypertension, including the use of selective angiotensin II and bradykinin receptor antagonists, suggest additional vasodilator, non-renin-dependent mechanisms in their action on blood flow and blood pressure. Inhibition of kinin degradation by ACE inhibitors will amplify kinin-mediated reactions on local vessel tone, in particular, if kinin generation is stimulated or this situation is experimentally mimicked by addition of exogenous bradykinin. The acute blood pressure-lowering action of ACE inhibitors is inhibited by indomethacin-type cyclooxygenase inhibitors, suggesting a contribution of bradykinin-induced release of vasodilator prostaglandins to their action. Bradykinin stimulates the phospholipase-dependent release of arachidonic acid from membrane phospholipids, allowing for subsequent generation of its metabolites, the eicosanoids. This stimulation is receptor-mediated and involves one or more types of B2 receptors, coupled via G-proteins to intracellular messenger systems that control cytosolic calcium levels. Bradykinin-induced changes in vessel tone are transient, caused by a rapidly developing tachyphylaxis at the receptor level. The potent vasodilator action of systemic bradykinin administration is not consistently reflected in studies performed on isolated blood vessels. This is probably due to the indirect nature of kinin-mediated vasomotor responses, i.e., the release of vasoactive mediators, most notably the eicosanoids and endothelium-derived relaxing factor (EDRF).(ABSTRACT TRUNCATED AT 250 WORDS)


Gender, Attitudes Toward War, and Masculinities in Japan.
Previous studies have argued that masculinity is linked to war. We conducted a web-based survey to examine relationships between gender, attitudes toward war, and masculinities within a sample of Japanese adults of both sexes ( N = 366). Our results indicated that while men were more likely than women to accept war, the relationship between attitudes toward war and masculinities was inconclusive. Moreover, the results suggested that favorable attitudes toward war among men could be attenuated by interpersonal orientations. Based on our findings, we recommend a reexamination of attitudes toward war within the Japanese population.


Fluid drag reduction and efficient self-cleaning with rice leaf and butterfly wing bioinspired surfaces.
Researchers are continually inspired by living nature to solve complex challenges. For example, unique surface characteristics of rice leaves and butterfly wings combine the shark skin (anisotropic flow leading to low drag) and lotus leaf (superhydrophobic and self-cleaning) effects, producing the so-called rice and butterfly wing effect. In this paper, we present an overview of rice leaf and butterfly wing fluid drag and self-cleaning studies. In addition, we examine two other promising aquatic surfaces in nature known for such properties, including fish scales and shark skin. Morphology, drag, self-cleaning, contact angle, and contact angle hysteresis data are presented to understand the role of wettability, viscosity, and velocity. Liquid repellent coatings are utilized to recreate or combine various effects. Discussion is provided along with conceptual models describing the role of surface structures related to low drag, self-cleaning, and antifouling properties. Modeling provides design guidance when developing novel low drag and self-cleaning surfaces for applications in the medical, marine, and industrial fields.


Clinical Features of Children With Serology Negative, Biopsy Positive Celiac Disease.
The prevalence of pediatric serological negative celiac disease (SNCD) is poorly described, with few recognized clinical predictors beyond immunoglobulin A (IgA) deficiency or reduced gluten intake. The purpose of this retrospective review was to describe the prevalence of SNCD at the Stollery Children's Hospital and identify clinical features to help in recognition of these cases. Patients with a positive biopsy and negative serology (SNCD) were compared to those with positive biopsy and serology. SNCD diagnosis required clinical correlation and either confirmatory genetics or follow up endoscopy on a gluten-free diet. Of the 424 patients who met celiac disease (CD) criteria, 4.7% (n = 20) fulfilled our criteria for SNCD. There was a significant difference in the rates of IgA deficiency between the 2 groups, but no other clinical features were found that allowed for ready identification of SNCD patients.


Effect of exposure to light-at-night on life span and spontaneous carcinogenesis in female CBA mice.
The effect of constant illumination on the development of spontaneous tumors in female CBA mice was investigated. Fifty female CBA mice starting from the age of 2 months were kept under standard light/dark regimen (12 hr light:12 hr dark; LD) and 50 CBA mice of similar age were kept under constant illumination (24 hr a day, 2,500 Lux, LL). Exposure to the LL regimen decreased food consumption but did not influence body weight, significantly accelerated age-related disturbances in estrous function, and was followed by a significant increase in spontaneous tumor incidence in female CBA mice. Tumor incidence as well as the number of total or malignant tumors was significantly increased in the LL group compared to the LD group (p < 0.001). The incidence of lung adenocarcinomas, leukemias and hepatocarcinomas was 7/50; 6/50 and 4/50 in the LL group and 1/50; 0/50 and 0/50 in the LD group. Mice from the LL groups had shorter life spans then those from the LD group. The data demonstrate, for the first time, that exposure to constant illumination was followed by increases in the incidence of spontaneous lung carcinoma, leukemias and hepatocarcinoma in female CBA mice.


Tumor vascularization in cervical cancer by 3-dimensional power Doppler angiography: correlation with tumor characteristics.
To evaluate whether tumor vascularity as assessed by 3-dimensional power Doppler angiography (3D-PDA) correlates with some tumor features in cervical cancer. Clinical, sonographic, and histologic data on 56 women (mean age, 47.8 years; range, 27-81 years) with a diagnosis of carcinoma in the uterine cervix were analyzed. Tumor volume and 3D-PDA indexes (vascularization index, flow index, and vascularization flow index) were calculated in all cases. These data were correlated with some tumoral features such as histologic type, histologic grade, lymphovascular space involvement, lymph node metastases, and tumor stage. Intratumoral blood flow was found in all cases. No correlation was found between tumor volume and 3D-PDA indexes with histologic type, lymphovascular space involvement, and lymph node metastases. Moderately and poorly differentiated tumors and advanced-stage tumors had larger volume and 3D-PDA indexes (P < 0.05). Our data indicate that tumor vascularization as assessed by 3D-PDA correlates with some tumor features in cervical cancer.


Applications of Machine Learning in miRNA Discovery and Target Prediction.
MicroRNA (miRNA) is a small non-coding molecule that is involved in gene regulation and RNA silencing by complementary on their targets. Experimental methods for target prediction can be time-consuming and expensive. Thus, the application of the computational approach is implicated to enlighten these complications with experimental studies. However, there is still a need for an optimized approach in miRNA biology. Therefore, machine learning (ML) would initiate a new era of research in miRNA biology towards potential diseases biomarker. In this article, we described the application of ML approaches in miRNA discovery and target prediction with functions and future prospective. The implementation of a new era of computational methodologies in this direction would initiate further advanced levels of discoveries in miRNA.


Nest destruction elicits indiscriminate con- versus heterospecific brood parasitism in a captive bird.
Following nest destruction, the laying of physiologically committed eggs (eggs that are ovulated, yolked, and making their way through the oviduct) in the nests of other birds is considered a viable pathway for the evolution of obligate interspecific brood parasitism. While intraspecific brood parasitism in response to nest predation has been experimentally demonstrated, this pathway has yet to be evaluated in an interspecific context. We studied patterns of egg laying following experimental nest destruction in captive zebra finches, Taeniopygia guttata, a frequent intraspecific brood parasite. We found that zebra finches laid physiologically committed eggs indiscriminately between nests containing conspecific eggs and nests containing heterospecific eggs (of Bengalese finches, Lonchura striata vars. domestica), despite the con- and heterospecific eggs differing in both size and coloration. This is the first experimental evidence that nest destruction may provide a pathway for the evolution of interspecific brood parasitism in birds.


Olfactory neurons in bax knockout mice are protected from bulbectomy-induced apoptosis.
Surgical ablation of the olfactory bulb (bulbectomy) triggers a massive wave of apoptosis in mature olfactory sensory neurons within the olfactory epithelium. The aim of the current study was to determine if this process is dependent on expression of the pro-apoptotic protein Bax. Immunohistochemical detection of caspase-3 activation and olfactory epithelial thickness was used to demonstrate and quantify neuronal apoptosis in bax knockout and wild type mice, following bulbectomy. Caspase-3 activation and epithelial thinning were both reduced in the bax knockout mouse compared to the wild type mouse, at least up to 9 days post-bulbectomy, indicating that apoptosis was inhibited not just delayed. This study demonstrates that Bax plays a major role in olfactory neuron apoptosis following surgical deafferentation.


Conducting-angle-based percolation in the XY model.
We define a percolation problem on the basis of spin configurations of the two-dimensional XY model. Neighboring spins belong to the same percolation cluster if their orientations differ less than a certain threshold called the conducting angle. The percolation properties of this model are studied by means of Monte Carlo simulations and a finite-size scaling analysis. Our simulations show the existence of percolation transitions when the conducting angle is varied, and we determine the transition point for several values of the XY coupling. It appears that the critical behavior of this percolation model can be well described by the standard percolation theory. The critical exponents of the percolation transitions, as determined by finite-size scaling, agree with the universality class of the two-dimensional percolation model on a uniform substrate. This holds over the whole temperature range, even in the low-temperature phase where the XY substrate is critical in the sense that it displays algebraic decay of correlations.


TLR4 and C5aR crosstalk in dendritic cells induces a core regulatory network of RSK2, PI3Kβ, SGK1, and FOXO transcription factors.
Crosstalk between complement component 5a receptors (C5aRs) and TLRs in dendritic cells (DCs) occurs upon pathogen invasion; however, studies on C5aR and TLR crosstalk mainly focused on the modulating effect of C5a on TLR-induced cytokine production. To elucidate the breadth of C5aR and TLR4 crosstalk, the effect of simultaneous treatment with C5a and LPS was investigated in human monocyte-derived DCs (moDCs) 2 h after stimulation using whole transcriptome sequencing analysis. Although the effect of C5a on hallmark genes defining TLR4-induced DC maturation was limited at this time point, RNA sequencing analysis revealed a great variety of novel C5a targets, of which many interfere with TLR4-mediated immune activation. Analysis of functional relationships among these genes uncovered induction of a central immune regulatory network upon C5aR and TLR4 crosstalk, involving the transcription factors forkhead box (FOX)O1 and FOXO3 and the signaling molecules serum- and glucocorticoid-inducible kinase (SGK1), ribosomal S6 kinase 2 (RSK2), and PI3Kβ. C5aR and TLR crosstalk, furthermore, yielded down-regulation of mainly proinflammatory network branches, including IL-12B, IL-2Rα (IL-2RA), and jagged 1 (JAG1) and cooperative induction of predominantly anti-inflammatory network branches, including sphingosine kinase 1 (SPHK1), β2 adrenergic receptor (ADRB2), gastric inhibitory polypeptide receptor (GIPR), and four-and-a-half Lin11, Isl-1, and Mec-3 domains protein 2 (FHL2). Together, these data point toward induction of generalized immune regulation of DC function. Motif enrichment analysis indicate a prominent role for basic leucine zipper (bZIP) and IFN regulatory factor 4 (IRF4) transcription factors upon C5aR and TLR4 crosstalk. Additionally, differences were observed in the modulating capacity of C5a on DCs in the absence or presence of a pathogen (TLR stimulus). Our findings shed new light on the depth and complexity of C5aR and TLR4 crosstalk and provide new foci of research for future studies.


Cellular immunity analysis using monoclonal antibodies in human glomerulonephritis.
Monoclonal antibodies against class II antigens of the human major histocompatibility complex (MHC) (Edu 1), von Willebrand factor-related antigen marker of endothelial cell, T cells (Cris 1), helper/inducer T cells (T4) and cytotoxic/suppressor T cells (T8) by indirect immunofluorescence, and stain for nonspecific esterase characterizing monocytes-macrophages (Mo-Ma) were applied in 64 renal biopsies--54 glomerulonephritis (GN), 10 non-GN- and in 14 normal kidneys. Class II antigens were expressed on the endothelium of renal microvasculature in all specimens. Intraglomerular T cells and Mo-Ma were only present in GN. Mo-Ma appeared associated with endo- and extracapillary proliferation (Xc2 = 4.68; p less than 0.05), C3 (X2 = 4.21; p less than 0.05), and fibrinogen (X2 = 3.84; p less than 0.05) deposition; and those were most numerous in biopsies with intraglomerular T cells. Interstitial MHC-class II+ cells (Xc2 = 5.5; p less than 0.02), T cells (F = 3.37; p less than 0.005) and Mo-Ma (F = 2.45; p less than 0.05) were significantly higher in GN with endo- or extracapillary proliferation than in the remaining. In GN, correlations were seen between T cells and MHC-class II+ cells (r = 0.63; p less than 0.001), and Mo-Ma (r = 0.38; p less than 0.02), infiltrating the interstitium. Our results suggest that both humoral and cellular immunity contribute to macrophage glomerular infiltration in the human GN. Mononuclear cells, and no intrinsic renal cells, would be implicated in the cellular immune interactions in situ.


Draft Genome Sequence of the Immunobiotic Strain Lactobacillus jensenii TL2937.
The genome of the immunomodulatory strain Lactobacillus jensenii TL2937 is described here. The draft genome has a total length of 1,678,416 bp, a G+C content of 34.3%, and 1,470 predicted protein-coding sequences. The genome information will be useful for gaining insight into the immunomodulatory properties of the TL2937 strain in the porcine host.


Electron-Nuclear Coherent Coupling and Nuclear Spin Readout through Optically Polarized VB- Spin States in hBN.
Coherent coupling of defect spins with surrounding nuclei along with the endowment to read out the latter are basic requirements for an application in quantum technologies. We show that negatively charged boron vacancies (VB-) in hexagonal boron nitride (hBN) meet these prerequisites. We demonstrate Hahn-echo coherence of the VB- spin with a characteristic decay time Tcoh = 15 μs, close to the theoretically predicted limit of 18 μs for defects in hBN. Elongation of the coherence time up to 36 μs is demonstrated by means of the Carr-Purcell-Meiboom-Gill decoupling technique. Modulation of the Hahn-echo decay is shown to be induced by coherent coupling of the VB- spin with the three nearest 14N nuclei via a nuclear quadrupole interaction of 2.11 MHz. DFT calculation confirms that the electron-nuclear coupling is confined to the defective layer and stays almost unchanged with a transition from the bulk to the single layer.


[Effect of pancreatico-biliary diversion on endogenous CCK secretion, pancreatic enzyme synthesis, and amylase release].
Pancreatico-biliary diversion (PBD) by jejunal transposition in rats caused pronounced hyperplasia of pancreas. The increase of pancreatic trypsinogen contents exceeded the pancreatic growth, while pancreatic lipase and amylase contents relatively reduced. The high level of plasma CCK at the early period of PBD gradually decreased. The plasma secretin levels remained unchanged for 14 days after PBD. The plasma CCK levels were not elevated in fasting, but increased after intrajejunal infusion of 0.1 N HCl or Clinimeal. In acini prepared from PBD rats, the responsiveness to CCK8 was decreased when amylase release was expressed relative to DNA. The dose-response curve for CCK8 was shifted 3 fold toward higher concentrations of CCK8 4 days after PBD, but on 7 and 14 days after PBD returned to the same curve as the transected rats (control).


Power amplification for 1.6 µm high-order vortex modes.
1.6 µm high-order vortex modes carrying orbital angular momentums (OAMs) play significant roles in long-range Doppler lidars and other remote sensing. Amplification of 1.6 µm high-order vortex modes is an important way to provide high-power laser sources for such lidars and also enable the weak echo signal to be amplified so that it can be analyzed. In this work, we propose a four-pass Er:YAG vortex master-oscillator-power-amplification (MOPA) system to amplify 1.6 µm high-order vortex modes. In the proof-of-concept experiments, 1.6 µm single OAM mode (l = 3) is amplified successfully and the gain ranging from 1.88 to 2.36 is achieved. Multiplexed OAM mode (l=±3) is also amplified with favorable results. This work addresses the issue as the low gain of Er:YAG vortex MOPA, which provides a feasible path for 1.6 µm high-order vortex modes amplification.


CD30-targeted oncolytic viruses as novel therapeutic approach against classical Hodgkin lymphoma.
Classical Hodgkin lymphoma (cHL) is a hematopoietic malignancy with a characteristic cellular composition. The tumor mass is made up of infiltrated lymphocytes and other cells of hematologic origin but only very few neoplastic cells that are mainly identified by the diagnostic marker CD30. While most patients with early stage cHL can be cured by standard therapy, treatment options for relapsed or refractory cHL are still not sufficient, although immunotherapy-based approaches for the treatment of cHL patients have gained ground in the last decade. Here, we suggest a novel therapeutic concept based on oncolytic viruses selectively destroying the CD30+-positive cHL tumor cells. Relying on a recently described CD30-specific scFv we have generated CD30-targeted measles virus (MV-CD30) and vesicular stomatitis virus (VSV-CD30). For VSV-CD30 the VSV glycoprotein G reading frame was replaced by those of the CD30-targeted MV glycoproteins. Both viruses were found to be highly selective for CD30-positive cells as demonstrated by infection of co-cultures of target and non-target cells as well as through blocking infection by soluble CD30. Notably, VSV-CD30 yielded much higher titers than MV-CD30 and resulted in a more rapid and efficient killing of cultivated cHL-derived cell lines. Mouse tumor models revealed that intratumorally, as well as systemically injected VSV-CD30, infected cHL xenografts and significantly slowed down tumor growth resulting in a substantially prolonged survival of tumor-bearing mice. Taken together, the data support further preclinical testing of VSV-CD30 as novel therapeutic agent for the treatment of cHL and other CD30+-positive malignancies.


[Optimization of Control of Blood Pressure, Metabolic Disorders and Target Organs Protection With Fixed Perindopril and Indapamide Combination in Treated Patients With Arterial Hypertension].
to assess the potential of fixed perindopril/indapamide combination (FPIC) to improve angioprotection in patients with arterial hypertension (AP) with various efficacy of preceding therapy with combination of losartan and hydrochlorothiazide (HCTZ). We included in this open study 50 patients with AP divided into two equal-sized groups in dependence on the achievement of target blood pressure (BP) less than 140/90 mm Hg on preceding therapy with losartan (100 mg) and HCTZ (12.5 mg). All patients underwent ambulatory BP monitoring (ABPM), applanation tonometry (assessment of augmentation index and central blood pressure), measurement of pulse wave velocity (PWV), laboratory tests (lipid profile, fasting glucose, HOMA index, homocysteine, leptin, adiponectin, high sensitivity C reactive protein [hsCRP]). Study duration was 12 weeks. Treatment with FPIC in patients not at target BP provided 14.5 and 6.6% reduction of systolic and diastolic BP (SBP and DBP), respectively (p<0.01), while in patients with target BP it was associated with additional reductions of SBP and DBP by 3.9 and 5.4%, respectively (p<0.01). According to ABPM data average day- and nighttime SBP decreased by 16.9 and 15.0%, average day- and nighttime DBP - by 10.6 and 13.6% (p<0.01) in the group of patients not at target BP. Reductions of PWV (by 15.2 and 2.2%), augmentation index (by 10.7 and 9.4%), central SBP (by 10.9 and 2.1%), central pulse BP vascular age (by 8.7 and 6.0%) were observed in groups of patients without and with target BP on preceding therapy, respectively (p<0.01). Leptin level decreased by 10.0 and 14.4%, hsCRP - by 17.7 and 11.0%; while level of adiponectin increased by 6.7 and 9.9% (p<0.01). Our results demonstrated advantages of FPIC over losartan+HCTZ combination relative to BP control, improvement of arterial elasticity, alleviation of insulin resistance and inflammation.


Diagnosis of congenital toxoplasmosis: comparison of targets for detection of Toxoplasma gondii by PCR.
Three PCR targets (18S ribosomal DNA, B1, and AF146527) and mouse inoculation were compared for 83 samples in the context of congenital toxoplasmosis. These four techniques are not statistically different in terms of sensitivity and specificity. However, further analysis highlighted problems sometimes encountered with PCR diagnosis of congenital toxoplasmosis.


Successful anesthetic management of a giant lower lip hemangioma patient using high flow nasal cannula -a case report.
Giant lip hemangioma is a rare disease that may cause difficulty in preoxygenation and ventilation when using face masks and intubation during general anesthesia induction. A laparoscopic cholecystectomy was planned for a 77-year-old woman. The patient had a giant lower lip hemangioma that was 12 x 5 x 5 cm, which made preoxygenation and ventilation through a face mask impossible and put her at risk of hemangioma rupture. We preoxygenated her through a high-flow nasal cannula (HFNC). Following propofol and succinylcholine administration, we intubated the patient with a video laryngoscope without desaturation, hemangioma rupture, or CO2 retention. HFNC is a useful tool when difficult intubation is expected in patients who have problems using conventional face masks.


High-Pressure Hand Injection Injury Case Report.
High-pressure injection injuries present to trauma centers a few times each year, typically involving the patient's non-dominant hand.1-6 Symptoms may include progressive pain, numbness, swelling of the affected area, and decreased range of motion.2,6-8 These injuries are important to recognize because the initial injury can involve damage to ligaments, tendons, and neurovascular structures.1-5 Pressure increases, from the injected material and subsequent tissue swelling, can result in vascular injury and compartment syndrome.1,2,5 Antibiotics and prompt surgical evaluation are vital because high-pressure injection injuries are considered a surgical emergency.1,2,7-9. High-pressure injection injuries, hand injuries, orthopedics.


Novel CARMIL2 (RLTPR) Mutation Presenting with Hyper-IgE and Eosinophilia: A Case Report.
Inborn errors of immunity are a growing group of disorders with a wide spectrum of genotypic and phenotypic profiles. CARMIL2 (previously named RLTPR) deficiency is a recently described cause of immune dysregulation, mainly presenting with allergy, mucocutaneous infections, and inflammatory bowel disease. CARMIL2 deficiency is categorized under diseases of immune dysregulation with susceptibility to lymphoproliferative conditions. Here we describe a 29-years-old male from a consanguineous family, with food and sting allergy, allergic rhinitis, facial molluscum contagiosum (viral infection of the skin in the form of umbilicated papules), eosinophilia and highly elevated serum IgE level. Whole exome sequencing revealed numerous homozygous variants, including a CARMIL2 nonsense mutation, a gene regulating actin polymerization, and promoting cell protrusion formation. The selective role of CARMIL2 in T cell activation and maturation through cyto-skeletal organization is proposed to be the cause of immune dysregulation in individuals with CARMIL2 deficiency. CARMIL2 has an important role in immune pathways regulation, through cell maturation and differentiation, giving rise to a balance between Th1, Th2, and Th17 immune response. This case can improve the understanding of the different impacts of CARMIL2 mutations on immune pathways and further guide the diagnosis of patients with similar phenotypes.


Characterization of IS1474, an insertion sequence of the IS21 family isolated from Pseudomonas alcaligenes NCIB 9867.
A new insertion sequence (IS) designated IS1474 was isolated from Pseudomonas alcaligenes NCIB 9867 (P25X). IS1474 is a 2632 bp element which showed a characteristic IS structure with 12 bp inverted repeats (IRs) flanking a 2608 bp central region. IS1474 contained four open reading frames (ORF1-ORF4), two in each orientation. Similarities were detected between ORF1 and ORF2 and the putative transposases of the IS21 family. Sequences upstream from IS1474 were found to display up to 89% homology with IS53 from Pseudomonas syringae suggesting that IS1474 had inserted into another related IS element designated IS1475. An open reading frame, ORF5, located at the junction of IS1474 and IS1475, showed similarities with the IstB protein of IS21 and could possibly be the transposase subunit of IS1475. Transposition assays showed that IS1474 transposed at a relatively low frequency leading to cointegration with target plasmids. Hybridization studies showed that IS1474 is present in at least 13 copies in the chromosome of P25X and one copy on its endogenous plasmid.


Building high-impact science: the dean as innovator.
If funding level is accepted as an empirical referent of research productivity, the nursing profession's relatively low volume of funded research puts its capacity to influence practice and policy based on scientific evidence at a disadvantage. For the profession to effectively compete with other "high-impact," health-related disciplines, nursing leaders must find ways for a greater proportion of nursing faculty to excel as scientists, producing sufficient volume and quality of work in their careers to have a major influence on health care. In addition, if nursing leaders are to enhance nurses' interest in scientific development and use, the academic environment needs to foster greater connectivity of students at all levels of education with the scientific enterprise.


Asthma is associated with a lower incidence of metastatic colorectal cancer in a US patient cohort.
In previous pre-clinical studies, we examined the contribution of interleukin 4 receptor (IL4R) signaling in the progression and metastasis of colorectal cancer (CRC). Aberrant activation of this receptor can result in atopic diseases such as asthma. We hypothesized that further evidence for the contribution of excessive IL4R being associated with CRC progression could be seen in medical records, and specifically that chronic asthma patients were more likely to be diagnosed with metastatic CRC. To test this hypothesis, we took advantage of the Synthetic Derivative, a resource developed at Vanderbilt University Medical Center that hosts de-identified data taken from the electronic medical record. We developed search protocols that produced retrospective cohorts of invasive CRC patients and cancer-free equivalents. In comparing 787 metastatic CRC patients to 238 non-metastatic patients, we actually found significantly fewer asthmatics went on to develop metastatic CRC (P=0.0381). By comparing these groups together against 1197 cancer-free patients, even fewer asthmatic patients would develop invasive CRC (P<0.0001). While these results are clearly in opposition to our original hypothesis, they still support a link between chronic asthma and metastatic CRC development. One intriguing possibility, that will be examined in the future, is whether treatment for chronic asthma may be responsible for the reduction in metastatic cancer.


Rapidly maturing red fluorescent protein variants with strongly enhanced brightness in bacteria.
A rapidly maturing variant of the red fluorescent protein DsRed was optimized for bacterial expression by random mutagenesis. The brightest variant contains six mutations, two of which (S4T and a silent mutation in codon 2) explain most of the fluorescence enhancement. The novel variants are expressed at 9-60-fold higher levels in Escherichia coli compared to DsRed.T3, but are not superior fluorophores on a per molecule basis. In contrast to previously available DsRed variants, DsRed.T3_S4T is sufficiently bright to monitor Salmonella gene expression in infected animals using flow cytometry. However, no fluorescence enhancement was observed in Leishmania or HeLa cells, indicating that these novel variants are specifically useful for bacteria.


Analysis of Chemical Signatures of Alkaliphiles using Fatty Acid Methyl Ester Analysis.
Fatty acids occur in nearly all living organisms as the important predominant constituents of lipids. While all fatty acids have essentially the same chemical nature, they are an extremely diverse group of compounds. To test the hypothesis, fatty acids of alkaliphiles isolates, Bacillus subtilis SVUNM4, Bacillus licheniformis SVUNM8, Bacillus methylotrohicus SVUNM9, and Paenibacillus dendritiformis SVUNM11, were characterized compared using gas chromatography-mass spectrometry (GC-MS) analysis. The content of investigated ten fatty acids, 1, 2-benzenedicarboxylic acid butyl 2-methylpropyl ester, phthalic acid, isobutyl 2-pentyl ester, dibutyl phthalate, cyclotrisiloxane, hexamethyl, cyclotetrasiloxane, octamethyl, dodecamethyl, heptasiloxane 1,1,3,3,5,5,7,7,9,9,11,11,13,13-etradecamethyl, 7,15-dihydroxydehydroabietic acid, methyl ester, di (trimethylsilyl) ether, hentriacontane, 2-thiopheneacetic acid, undec-2-enyl ester, obviously varied among four species, suggesting each species has its own fatty acid pattern. These findings demonstrated that GC-MS-based fatty acid profiling analysis provides the reliable platform to classify these four species, which is helpful for ensuring their biotechnological interest and novel chemotaxonomic.


The protective effects of lafutidine for bortezomib induced peripheral neuropathy.
Peripheral neuropathy (PN) caused by bortezomib is an important complication of multiple myeloma. Subcutaneous injection of bortezomib reduced PN, but 24% of cases were grade 2 PN and 6% of cases were grade 3 PN. PN higher than grade 2 was not resolved by subcutaneous injection. PN higher than grade 3 has serious dose limiting toxicity and is the cause of discontinuing bortezomib treatment. Lafutidine is an H2-blocker with gastroprotective activity and is thought to function by increasing mucosal blood flow via capsaicin sensitive neurons. The same activity of lafutidine is considered to improve glossodynia and taxane induced PN. We hypothesized that lafutidine prevents or improves PN that is caused by bortezomib. In the current study, bortezomib was administered in the usual manner (intravenous administration of bortezomib 1.3 mg/m(2), twice a week for 2 weeks, followed by 1 week without treatment) for up to four cycles to compare our data with other studies. Lafutidine was administered orally at a dose of 10 mg twice daily. In our eight evaluated cases, the total occurrence of PN was four out of eight patients (50%). There were only grade 1 PN (4 out of 8) cases, and no cases higher than grade 2. We conclude that (1) the total occurrence of PN was not improved, (2) there was no PN after the first course, (3) there were only grade 1 cases and there were no cases higher than grade 2, and (4) no cases discontinued bortezomib treatment because of PN. This is the first report showing that lafutidine is useful for the amelioration of bortezomib induced PN.


Adaptation of A-to-I RNA editing in Drosophila.
Adenosine-to-inosine (A-to-I) editing is hypothesized to facilitate adaptive evolution by expanding proteomic diversity through an epigenetic approach. However, it is challenging to provide evidences to support this hypothesis at the whole editome level. In this study, we systematically characterized 2,114 A-to-I RNA editing sites in female and male brains of D. melanogaster, and nearly half of these sites had events evolutionarily conserved across Drosophila species. We detected strong signatures of positive selection on the nonsynonymous editing sites in Drosophila brains, and the beneficial editing sites were significantly enriched in genes related to chemical and electrical neurotransmission. The signal of adaptation was even more pronounced for the editing sites located in X chromosome or for those commonly observed across Drosophila species. We identified a set of gene candidates (termed "PSEB" genes) that had nonsynonymous editing events favored by natural selection. We presented evidence that editing preferentially increased mutation sequence space of evolutionarily conserved genes, which supported the adaptive evolution hypothesis of editing. We found prevalent nonsynonymous editing sites that were favored by natural selection in female and male adults from five strains of D. melanogaster. We showed that temperature played a more important role than gender effect in shaping the editing levels, although the effect of temperature is relatively weaker compared to that of species effect. We also explored the relevant factors that shape the selective patterns of the global editomes. Altogether we demonstrated that abundant nonsynonymous editing sites in Drosophila brains were adaptive and maintained by natural selection during evolution. Our results shed new light on the evolutionary principles and functional consequences of RNA editing.


Serum Soluble ST2 and Diastolic Dysfunction in Hypertensive Patients.
Echocardiographic evaluation of left ventricular (LV) structural and functional alterations in hypertension has some limitations, potentially overcome by using biomarkers. ST2, a prognostic biomarker for heart failure and myocardial infarction patients, was less studied in hypertension. To analyze the relationship between serum ST2 levels and diastolic dysfunction (DD) in hypertension. We enrolled 88 hypertensive outpatients (average age 65 years, 69.3% females) in a prospective study, stratified for presence of LV hypertrophy (LVH). For each patient clinical examination, lab workup (routine and serum ST2 levels) and echocardiography were performed. Hypertensive patients with LVH had higher age, pulse pressure, mean arterial pressure, and serum ST2, while having lower serum albumin than those without LVH. Serum ST2 levels correlate with parameters of LV remodeling and DD. We found that 5.3% of ST2 level variability was caused by a 1-unit variation of cardiovascular risk. We identified cut-off values for discriminating hypertension with LVH versus that without LVH and grade 2 DD versus normal diastolic performance. ST2 could be used as diagnostic biomarker for cardiac remodeling and altered diastolic performance in hypertension, providing additional data to echocardiography. It could represent a milestone in early detection of cardiac performance alteration.


Theoretical study of Gibbs free energy and NMR chemical shifts, of the effect of methyl substituents on the isomers of (E)-1-(α,Ꞵ-Dimethylbenzyliden)-2,2-diphenylhydrazine.
A theoretical analysis of free Gibbs Energy and NMR 1H 13C chemical shifts of the effect of introduce methyl groups on diphenyl rings, to produce different isomers of (E)-1-(α,Ꞵ-dimethylbenzylidene)-2,2-diphenylhydrazine, is presented. IR vibrational frequencies, Mulliken charges, molecular electrostatic potential (MEP), Gibbs free energy (G) and 1H- and 13C-NMR chemical shifts were obtained by theoretical calculations. In this analysis it was found that the position of the methyl group affects the values of the 1H- and 13C-NMR chemical shifts and the ∆G and ∆H thermodynamic properties of formation and reaction, these properties vary with the same trend, for the isomers studied. Gibbs free energy calculations show that the theoretical (E)-1-(3,4-Dimethylbenzylidene)-2,2-diphenylhydrazine isomer is the most stable, which explains the success of the experimental synthesis of this compound among the other isomers. For this molecule, the C of the HC=N group is the most nucleophilic and the H is the least acidic. The 1H-NMR chemical shifts of protons show a strong correlation with the C=N distance. It was also observed that methyl affects the ν(C=N) frequencies, the C=N distance increases when the inductive effect of the methyl groups is in the structure.


The direct disease burden of COVID-19 in Belgium in 2020 and 2021.
Burden of disease estimates have become important population health metrics over the past decade to measure losses in health. In Belgium, the disease burden caused by COVID-19 has not yet been estimated, although COVID-19 has emerged as one of the most important diseases. Therefore, the current study aims to estimate the direct COVID-19 burden in Belgium, observed despite policy interventions, during 2020 and 2021, and compare it to the burden from other causes. Disability-adjusted life years (DALYs) are the sum of Years Lived with Disability (YLDs) and Years of Life Lost (YLLs) due to disease. DALYs allow comparing the burden of disease between countries, diseases, and over time. We used the European Burden of Disease Network consensus disease model for COVID-19 to estimate DALYs related to COVID-19. Estimates of person-years for (a) acute non-fatal disease states were calculated from a compartmental model, using Belgian seroprevalence, social contact, hospital, and intensive care admission data, (b) deaths were sourced from the national COVID-19 mortality surveillance, and (c) chronic post-acute disease states were derived from a Belgian cohort study. In 2020, the total number of COVID-19 related DALYs was estimated at 253,577 [252,541 - 254,739], which is higher than in 2021, when it was 139,281 [136,704 - 142,306]. The observed COVID-19 burden was largely borne by the elderly, and over 90% of the burden was attributable to premature mortality (i.e., YLLs). In younger people, morbidity (i.e., YLD) contributed relatively more to the DALYs, especially in 2021, when vaccination was rolled out. Morbidity was mainly attributable to long-lasting post-acute symptoms. COVID-19 had a substantial impact on population health in Belgium, especially in 2020, when COVID-19 would have been the main cause of disease burden if all other causes had maintained their 2019 level.


Updated results from the phase 3 HELIOS study of ibrutinib, bendamustine, and rituximab in relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma.
We report follow-up results from the randomized, placebo-controlled, phase 3 HELIOS trial of ibrutinib+bendamustine and rituximab (BR) for previously treated chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) without deletion 17p. Overall, 578 patients were randomized 1:1 to either ibrutinib (420 mg daily) or placebo, in combination with 6 cycles of BR, followed by ibrutinib or placebo alone. Median follow-up was 34.8 months (range: 0.1-45.8). Investigator-assessed median progression-free survival (PFS) was not reached for ibrutinib+BR, versus 14.3 months for placebo+BR (hazard ratio [HR] [95% CI], 0.206 [0.159-0.265]; P < 0.0001); 36-month PFS rates were 68.0% versus 13.9%, respectively. The results are consistent with the primary analysis findings (HR = 0.203, as assessed by independent review committee, with 17-month median follow-up). Median overall survival was not reached in either arm; HR (95% CI) for ibrutinib+BR versus placebo: 0.652 (0.454-0.935; P = 0.019). Minimal residual disease (MRD)-negative response rates were 26.3% for ibrutinib+BR and 6.2% for placebo+BR (P < 0.0001). Incidence of treatment-emergent adverse events (including grades 3-4) were generally consistent with the initial HELIOS report. These long-term data support improved survival outcomes and deepening responses with ibrutinib+BR compared with BR in relapsed CLL/SLL.


Synaptic congenital myasthenic syndrome in three patients due to a novel missense mutation (T441A) of the COLQ gene.
Congenital myasthenic syndromes (CMS) with deficiency of endplate acetylcholinesterase (AChE) are caused by mutations in the synapse specific collagenic tail subunit gene (COLQ) of AChE. We identified a novel missense mutation (T441A) homozygously in three CMS patients from two unrelated German families. The mutation is located in the C-terminal region of the ColQ protein, which initiates assembly of the triple helix, and is essential for insertion of the tail subunit into the basal lamina. Density gradient analysis of AChE extracted from muscle of one of the patients revealed the absence of asymmetric AChE. All patients were characterized by an onset of disease in childhood, exercise-induced proximal weakness, absence of ptosis and ophthalmoparesis, a decremental EMG response, and deterioration in response to anticholinesterase drugs. However, age at onset, disease progression, disease severity, and functional impairment varied considerably among the three patients. As adults, two siblings from one family experience only mild impairment, while the third patient requires a wheelchair for most of the day and assisted ventilation at night.


Self-Cognizant Bionic Liquid Sensor for Pathogen Diagnosis.
As observed in the outbreaks of SARS and swine flu, as well as many other infectious diseases, the huge volume of human traffic across numerous enclosed public venues has posed immense challenges to preventing the spread of communicable diseases. There is an urgent need for effective disease surveillance management in public areas under pandemic outbreaks. The physicochemical properties associated with ionic liquids make them particularly suited for molecular communications in sensing networks where low throughput is quite adequate for pathogen detection. This paper presents a self-cognizant system for rapid diagnosis of infectious disease using a bionic sensor such that testing can be supported without collecting a fluid sample from a subject through any invasive methods. The system is implemented for testing the performance of the proposed bionic liquid sensing network.


Genomic prediction of starch content and chipping quality in tetraploid potato using genotyping-by-sequencing.
Genomic prediction models for starch content and chipping quality show promising results, suggesting that genomic selection is a feasible breeding strategy in tetraploid potato. Genomic selection uses genome-wide molecular markers to predict performance of individuals and allows selections in the absence of direct phenotyping. It is regarded as a useful tool to accelerate genetic gain in breeding programs, and is becoming increasingly viable for crops as genotyping costs continue to fall. In this study, we have generated genomic prediction models for starch content and chipping quality in tetraploid potato to facilitate varietal development. Chipping quality was evaluated as the colour of a potato chip after frying following cold induced sweetening. We used genotyping-by-sequencing to genotype 762 offspring, derived from a population generated from biparental crosses of 18 tetraploid parents. Additionally, 74 breeding clones were genotyped, representing a test panel for model validation. We generated genomic prediction models from 171,859 single-nucleotide polymorphisms to calculate genomic estimated breeding values. Cross-validated prediction correlations of 0.56 and 0.73 were obtained within the training population for starch content and chipping quality, respectively, while correlations were lower when predicting performance in the test panel, at 0.30-0.31 and 0.42-0.43, respectively. Predictions in the test panel were slightly improved when including representatives from the test panel in the training population but worsened when preceded by marker selection. Our results suggest that genomic prediction is feasible, however, the extremely high allelic diversity of tetraploid potato necessitates large training populations to efficiently capture the genetic diversity of elite potato germplasm and enable accurate prediction across the entire spectrum of elite potatoes. Nonetheless, our results demonstrate that GS is a promising breeding strategy for tetraploid potato.


The Usefulness of Rare Blood Group Systems in the Risk Determination for Severe COVID-19.
The newly identified human coronavirus was named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), based on a detailed analysis of clinical manifestation. It was reported that blood type O individuals were less likely to become infected by SARS-CoV, while blood type A individuals have an increased risk of severe illness. The Forssman antigen, or Forssman glycolipid synthase (FS), was first described in 1911 by John Frederick Forssman. Blood type A/B glycosyltransferases (AT/BTs) and Forssman glycolipid synthase (FS) are encoded by the evolutionarily related ABO (A/B alleles) and GBGT1 genes. In this article, based on published studies about the pathogenesis of the COVID-19, we hypothesize the possible relationship between the COVID-19 infection and rare blood type systems, such as the Forssman antigen system.


Synthesis of aspartame precursor: alpha-L-aspartyl-L-phenylalanine methyl ester in ethyl acetate using thermolysin entrapped in polyurethane.
Cross-linked polyurethane (PU) was prepared for entrapping thermolysin. Using the immobilized thermolysin (IT), Z-L-aspartic acid (ZA) was reacted with -Lphenylalanine methyl ester (L-PM) in water-saturated ethyl acetate to give only alpha-Z-L-aspartylL-phenylalanine methyl ester (alpha-ZAPM). Ninety-four percent conversion of alpha-ZAPM was obtained for 30 h of reaction at 40 degrees C when 46 mg of enzyme was entrapped. PU support prepared from polypropylene glycol (#2000) showed better properties than from polypropylene (#1000) and polyethylene (#1000). Addition of polyol could increase the gel fraction of PU. The IT PU-ll-G-3, prepared from 1/2 mole ratio of PPG (#2000)/glycerin, gave the highest gel fraction and best swelling, and 89.0% of residual activity was obtained after four times of reuse (72 h). The stability of immobilized thermolysin was good; the activity loss resulting from degradatin and leak of enzyme in each time of reuse were found only about 2%. The kinetics of immobilized thermolysin-catalyzed condensation reaction of ZA with L-PM in water-saturated ethyl acetate was found to be first order in L-PM and the Lineweaver-Burk plot of 1/V against 1/[ZA] yields a straight line, showing that the reaction involves consecutive reactions of ZA and L-PM with the immobilized enzyme and with the ZA-immobilized enzyme complex, with the second reaction being the rate determining step.


Structurally Diverse Phenolic Amides from the Fruits of Lycium barbarum with Potent α-Glucosidase, Dipeptidyl Peptidase-4 Inhibitory, and PPAR-γ Agonistic Activities.
A total of nine new phenolic amides (1-9), including four pairs of enantiomeric mixtures (3-5 and 8), along with ten known analogues (10-19) were identified from the fruits of Lycium barbarum using bioassay-guided chromatographic fractionation. Their structures were elucidated by comprehensive spectroscopic and spectrometric analyses, chiral HPLC analyses, and quantum NMR, and electronic circular dichroism calculations. Compounds 5-7 are the first example of feruloyl tyramine dimers fused through a cyclobutane ring. The activity results indicated that compounds 1, 11, and 13-17 exhibited remarkable inhibition against α-glucosidase with IC50 of 1.11-33.53 μM, 5-150 times stronger than acarbose (IC50 = 169.78 μM). Meanwhile, compounds 4a, 4b, 5a, 5b, 13, and 14 exerted moderate agonistic activities for peroxisome proliferator-activated receptor (PPAR-γ), with EC50 values of 10.09-44.26 μM. Especially,compound 14 also presented inhibitory activity on dipeptidyl peptidase-4 (DPPIV), with an IC50 value of 47.13 μM. Furthermore, the banding manner of compounds 14 and 17 with the active site of α-glucosidase, DPPIV, and PPAR-γ was explored by employing molecular docking analysis.


Debottlenecking the 1,3-propanediol pathway by metabolic engineering.
The history of 1,3-propanediol (1,3-PD) conversion from being a specialty chemical to being a bulk chemical illustrates that the concerted effort of different metabolic engineering approaches brings the most successful results. In order to metabolically tailor the 1,3-PD production pathway multiple strategies have been pursued. Knocking-out genes responsible for by-products formation, intergeneric transfer and overexpression of the genes directly involved in the pathway, manipulation with internal redox balance, introduction of a synthetic flux control point, and modification of the substrate mechanism of transport are some of the strategies applied. The metabolic engineering of the microbial 1,3-PD production exploits both native producers and microorganisms with acquired ability to produce the diol via genetic manipulations. Combination of the appropriate genes from homologous and heterologous hosts is expected to bring a desired objective of production of 1,3-PD cheaply, efficiently and independently from non-renewable resources. The state-of-the-art of the 1,3-PD pathway metabolic engineering is reviewed in this paper.


Stereotactic fine-needle aspiration cytology of nonpalpable breast lesions: Institut Curie's experience of 243 histologically correlated cases.
The early diagnosis of nonpalpable breast lesions is a medical challenge because of the low specificity of different radiologic modalities. Fine-needle aspiration cytology (FNAC) assisted by a stereotactic guidance is an adjunctive diagnostic approach in the management of these lesions. The primary purpose of this article was to assess the diagnostic accuracy of FNAC in patients with nonpalpable breast lesions. Three hundred and seventy-one lesions from 357 patients (all female) underwent FNAC using the stereotactically guided technique. Of these cases, 243 lesions from 238 patients subsequently were acquired by surgical excisional biopsies and formed the basis of this study. Statistical analyses of the cytologic and the histologic diagnoses of these cases were performed. Histologically, 107 lesions (44%) were benign and 136 lesions (56%) were malignant. Of the 136 malignant lesions, cytology was concordant in 73 lesions (53.7%), suspicious in 15 lesions (11.0%), false-negative in 12 lesions (8.8%) (benign), and unsatisfactory in 36 lesions (26.5%). Among the 107 benign lesions, cytology was concordant with histology in 75 lesions (70.1%), whereas 4 lesions (3.7%) and 28 lesions (26.2%) were cytologically suspicious and unsatisfactory, respectively. No false-positive cytologies were found in the current series. The current prospective study indicates that mammography combined with FNAC provides an accurate and practical diagnostic approach for the majority of nonpalpable lesions. Patients with unsatisfactory and false-negative lesions should undergo excisional biopsy.


Out-of-Focal Plane Imaging by Leakage Radiation Microscopy.
Leakage radiation microscopy (LRM) is used to investigate the optical properties of surfaces. The front-focal plane (FFP) image with LRM reveals structural features on the surfaces. Back-focal plane (BFP) image with LRM reveals the angular distribution of the radiation. Herein we experimentally demonstrate that the out-of-focal plane (OFP) images present a link between the FFP and BFP images and provide optical information that cannot be resolved by either FFP or BFP images. The OFP image provides a linkage between the spatial location of the emission and the angular distribution from the same location, and thus information about the film's discontinuity, nonuniformity or variable thickness can be uncovered. The use of OFP imaging will extend the scope and applications of the LRM and coupled emission imaging which are powerful tools in nanophotonics and high throughput fluorescence screening.


Can pancreatitis be associated with amiodarone hepatotoxicity?
We report a patient with classical features of amiodarone hepatotoxicity who died of progressive liver failure. Throughout the course of his illness, he had epigastric pain, nausea, vomiting, and persistent mild to moderate elevation of amylase and lipase in his serum and peritoneal fluid. Pancreatitis due to amiodarone has not been reported. We raise the question of whether or not the pancreas is yet another organ subject to amiodarone toxicity and speculate as to possible pathogenesis. We suggest that patients on amiodarone who develop abnormal liver enzymes, nausea, vomiting, or abdominal pain be evaluated not only for hepatotoxicity, but for pancreatitis as well.


Porphyrin Donor and Tunable Push-Pull Acceptor Conjugates-Experimental Investigation of Marcus Theory.
We report on a series of electron donor-acceptor conjugates incorporating a ZnII -porphyrin-based electron donor and a variety of non-conjugated rigid linkers connecting to push-pull chromophores as electron acceptors. The electron acceptors comprize multicyanobutadienes or extended tetracyanoquinodimethane analogues with first reduction potentials ranging from -1.67 to -0.23 V vs. Fc+ /Fc in CH2 Cl2 , which are accessible through a final-step cycloaddition-retroelectrocyclization (CA-RE) reaction. Characterization of the conjugates includes electrochemistry, spectroelectrochemistry, DFT calculations, and photophysical measurements in a range of solvents. The collected data allows for the construction of multiple Marcus curves that consider electron-acceptor strength, linker length, and solvent, with data points extending well into the inverted region. The enhancement of electron-vibration couplings, resulting from the rigid spacers and, in particular, multicyano-groups in the conformationally highly fixed push-pull acceptor chromophores affects the charge-recombination kinetics in the inverted region drastically.


Solid-state 51V NMR investigation of the intercalation of alkylamines into layered alpha-vanadyl phosphate.
The intercalation behavior of layered alpha-phase vanadyl phosphate, alpha-VOPO(4).2H(2)O (alpha-VP), with alkylamine was investigated by (51)V solid-state NMR in combination with powder XRD. The XRD results show that the amines form bimolecular layers upon intercalation. For the intercalation with short chain amines (propylamine, pentylamine, and hexylamine), the C-C chain of the amines is tilted with respect to the inorganic basal plane. The amines with a longer alkyl chain (dodecylamine and hexadecylamine) tend to adopt an orientation where the C-C chain direction is perpendicular to the VP layer. For the amine with eight carbon atoms (octylamine), the intercalation results in two coexisting phases with different chain orientations. (51)V solid-state NMR was used to directly probe the effect of intercalation on the metal center environments. Both (51)V magic-angle spinning and static spectra of alpha-VP intercalated with different amines were obtained at different magnetic fields, and they are sensitive to intercalation. The intercalation induces the (51)V isotropic chemical shift to move toward deshielded direction. (51)V chemical shielding parameters such as the span are sensitive to the orientation of the amine chain with respect to the VP basal plane. For the V centers interacting with the amines having a tilted orientation, the (51)V span gradually decreases with increasing alkyl chain length. However, the span of the (51)V atoms interacting with the amines perpendicular to the VP layer is larger and independent of the length of the alkyl chain. The (51)V NMR data indicate that for the alpha-VPs intercalated with long-chain amines, such as dodecylamine and hexadecylamine, the amines can assume both tilted and perpendicular orientations.


Access to public sector family planning services and modern contraceptive methods in South Africa: A qualitative evaluation from community and health care provider perspectives.
Progress has been made to improve access to family planning services and contraceptive methods, yet many women still struggle to access contraception, increasing their risk for unintended pregnancy. This is also true for South Africa, where over fifty per cent of pregnancies are reported as unintended, even though contraception is freely available. There is also stagnation in the fertility rate indicators and contraceptive use data, indicating that there may be challenges to accessing contraception. This paper explores the evaluation of access to contraception from community and health care provider perspectives. This qualitative study explored factors affecting the uptake and use of contraception through focus group discussions (n = 14), in-depth interviews (n = 8), and drawings. Participants included male and female community members (n = 103) between 15 and 49 years of age, health care providers (n = 16), and key stakeholder informants (n = 8), with a total number of 127 participants. Thematic content analysis was used to explore the data using NVivo 10. Emergent themes were elucidated and thematically categorised. The results were categorised according to a priori access components. Overall, the results showed that the greatest obstacle to accessing contraception was the accommodation component. This included the effects of integrated care, long waiting times, and limited operational hours-all of which contributed to the discontinuation of contraception. Community members reported being satisfied with the accessibility and affordability components but less satisfied with the availability of trained providers and a variety of contraceptive methods. The accessibility and affordability themes also revealed the important role that individual agency and choice in service provider plays in accessing contraception. Data from the illustrations showed that adolescent males experienced the most geographic barriers. This study illustrated the importance of examining access as a holistic concept and to assess each component's influence on contraceptive uptake and use.


IgA-producing B cells in lung homeostasis and disease.
Immunoglobulin A (IgA) is the most abundant Ig in mucosae where it plays key roles in host defense against pathogens and in mucosal immunoregulation. Whereas intense research has established the different roles of secretory IgA in the gut, its function has been much less studied in the lung. This review will first summarize the state-of-the-art knowledge on the distribution and phenotype of IgA+ B cells in the human lung in both homeostasis and disease. Second, it will analyze the studies looking at cellular and molecular mechanisms of homing and priming of IgA+ B cells in the lung, notably following immunization. Lastly, published data on observations related to IgA and IgA+ B cells in lung and airway disease such as asthma, cystic fibrosis, idiopathic pulmonary fibrosis, or chronic rhinosinusitis, will be discussed. Collectively it provides the state-of-the-art of our current understanding of the biology of IgA-producing cells in the airways and identifies gaps that future research should address in order to improve mucosal protection against lung infections and chronic inflammatory diseases.


Prelabour Rupture of Membranes: Mode of Delivery and Outcome.
Pre-labour Rupture of Membranes (PROM) is an important cause of maternal and fetal morbidity and increased rate of cesarean section delivery. The aim of this study is to investigate the clinical characteristics, PROM-delivery interval, mode of delivery, and early maternal neonatal outcome among pregnant patients presenting with pre-labour rupture of membranes. This prospective case control study is implemented at the Obstetric and Gynecology Clinic of the University Clinical Center of Kosovo. The study included 100 pregnant patients presenting with prelabour rupture of membranes of which 63 were primigravida and 37 patients were multigravida. The incidence of cesarean section in this study is 28 % and the most common indications for cesarean delivery were fetal distress, malpresentation, cephalopelvic disproportion, and failed induction. The most common maternal complications in this study are chorioamnionitis, retained placenta and postpartum hemorrhage. Neonatal infectious morbidity was present in 16 % of cases. PROM is a significant issue for obstetricians and an important cause of maternal and neonatal morbidity and increased rate of cesarean section delivery.


Direct observation of ultrafast coherent exciton dynamics in helical π-stacks of self-assembled perylene bisimides.
Ever since the discovery of dye self-assemblies in nature, there have been tremendous efforts to exploit biomimetic supramolecular assemblies for tailored artificial photon processing materials. This feature necessarily has resulted in an increasing demand for understanding exciton dynamics in the dye self-assemblies. In a sharp contrast with J-type aggregates, however, the detailed observation of exciton dynamics in H-type aggregates has remained challenging. In this study, as we succeed in measuring transient fluorescence from Frenkel state of π-stacked perylene tetracarboxylic acid bisimide dimer and oligomer aggregates, we present an experimental demonstration on Frenkel exciton dynamics of archetypal columnar π-π stacks of dyes. The analysis of the vibronic peak ratio of the transient fluorescence spectra reveals that unlike the simple π-stacked dimer, the photoexcitation energy in the columnar π-stacked oligomer aggregates is initially delocalized over at least three molecular units and moves coherently along the chain in tens of femtoseconds, preceding excimer formation process.


Clinical characteristics according to sensitized allergens in adult korean patients with bronchial asthma.
Allergic sensitization is a risk factor for the development of bronchial asthma. This study was conducted to investigate clinical manifestations according to sensitized allergens in adult Korean patients with bronchial asthma. In total, 523 adult patients who were diagnosed with bronchial asthma between March 2002 and March 2008 were included in the study. All patients underwent skin prick tests for approximately 45 allergens or a specific IgE test. Sensitized allergens were grouped into the following categories: house dust mites, fungus, pollen, and animal dander. Atopy was defined as a positive skin prick test response or the presence of a specific IgE to one or more allergens. Of the 523 patients, 295 (56%) were sensitized to one or more allergens. A younger median age, greater proportion of males, higher eosinophil counts, and higher total IgE levels were observed in the atopic asthma group compared to the non-atopic asthma group. The PC20 value was negatively correlated with eosinophil counts and total IgE in the atopic asthma group. In the subgroup analysis, patients sensitized to Cladosporium showed poorer pulmonary function and a higher response to bronchodilators. In addition, patients sensitized to Alternaria showed severer bronchial hyperresponsiveness than non-atopic patients with asthma. Finally, a gradual increase in the number of sensitized allergens was noted with increasing age, eosinophil counts, and total IgE levels. We suggest the need for identifying the existence of atopy and exact offending allergens at the time of asthma diagnosis, since significant differences in sex, age, blood test results, and lung function were observed according to atopy and sensitized allergens.


Elevated glycosylation of CD36 in platelets is a risk factor for oxLDL-mediated platelet activation in type 2 diabetes.
Platelet activation and related cardiovascular complications are the hallmarks of type 2 diabetes (T2D). We investigated the mechanism of platelet activation in T2D using MS-based identification of differentially expressed platelet proteins with a focus on glycosylated forms. Glycosylation is considered one of the common post-translational modifications in T2D, and N/O-linked glycosylation of glycoproteins (GPs)/integrins is known to play crucial roles in platelet activation. Our platelet proteome data revealed elevated levels of GPs GPIbα, GPIIbIIIa, GPIV (CD36), GPV and integrins in T2D patients. T2D platelets had elevated N-linked glycosylation of CD36 at asparagine (Asn)408,417 . Enrichment analysis revealed a close association of glycosylated CD36 with thrombospondin-1, fibrinogen and SERPINA1 in T2D platelets. The glycosylation of CD36 has previously been reported to increase cellular uptake of long-chain fatty acids. Our in silico molecular docking data also showed a favorable binding of cholesterol with glycosylated Asn417 CD36 compared to the non-glycosylated form. We further investigated the CD36:LDL cholesterol axis in T2D. Elevated levels of oxidized-low density lipoprotein (oxLDL) were found to cause significant platelet activation via CD36-mediated stimulation of Lyn-JNK signaling. Sulfo-N-succinimidyl oleate, an inhibitor of CD36, effectively inhibited oxLDL-mediated platelet activation and adhesion in vitro. Our study suggests increased glycosylation of CD36 in T2D platelets as a potential route for oxLDL-mediated platelet activation. The oxLDL:CD36 axis may thus be exploited as a prospective target to develop therapeutics against thrombosis in T2D.


First report of strawberry polerovirus 1 in strawberry in Nepal.
Strawberry (Fragaria x ananassa Duch.) was introduced to Nepal from Japan in the 1990s, and thus, is a relatively new crop in the country. After the initial introduction of cultivar 'Nyoho' in Kakani, Nuwakot, different agencies and growers have introduced a number of cultivars in large numbers from Japan, Europe, America and India to expand the cultivation of strawberry in Nepal. Such practice has increased the risk of introducing new pathogens in the country. During a field visit at Kakani in October 2018, virus-like symptoms were observed in 5-10% of the plants in a polyhouse (~200 m2). Three strawberry leaf samples showing vein banding, vein clearing or tip necrosis with leaf puckering were collected. Total RNA was extracted from leaves using the RNeasy Plant Mini Kit (Qiagen, Germany) and subjected to high-throughput sequencing (HTS). After ribosomal RNA depletion using the Ribo-Zero rRNA kit, a cDNA library was prepared using an Illumina TruSeq Stranded Total RNA Kit and sequenced on an Illumina NovaSeq 6000 system (Macrogen Inc. Korea). De novo transcriptome assembly of the 67,748,658 reads with Trinity software (r20140717) yielded 116,854 contigs of 201-17,773 nucleotides (nt). BLASTn and BLASTx analysis of the contigs against the NCBI viral reference database showed that one contig with the nearly full genome sequence (5,968 nt, deposited under GenBank accssion number MZ355624) was identified as strawberry polerovirus 1 (SPV-1). A total of 10,401 reads was mapped to the reference SPV-1 nucleotide genome (GenBank accession number NC_025435) with a 263.2 sequence depth. The contig shared 99% nt sequence identity with SPV-1 isolate AB5301 (GenBank accession number KM233705) from Canada and 97% identity with the Argentine SPV-1 isolate 15CA (GenBank accession number MK142237). To confirm the presence of SPV-1, reverse transcription-PCR (RT-PCR) was performed using previously reported specific primers, SPV-1F (AGAGATCGCCGGATTCCGCAA) and SPV-1R (TGACACGCTCGGTATTCACAAACAG), amplifying 281 nt of the P1-P2 fusion protein gene (Thekke-Veetil and Tzanetakis 2016). Of the three samples, only one showing vein banding symptoms (Figure S1) was positive for SPV-1. Sanger sequencing of the RT-PCR products showed 100% nt identity with the HTS-derived sequence. SPV-1, a member of the genus Polerovirus in the family Solemoviridae, was first reported in strawberry showing decline symptom in Canada (Xiang et al. 2015), and was subsequently detected in the USA (Thekke-Veetil and Tzanetakis 2016) and in Argentina (Luciani et al. 2016; 2018). To our knowledge, this is the first report of SPV-1 infection in strawberry in Nepal and Asia.