Lp(a) lipoprotein in cardiovascular disease.
The article summarizes the increased knowledge about the enigmatic Lp(a) lipoprotein and its clinical importance over the past 20 years. The mode of inheritance, the unique features of Lp(a) composition and structure and the unusual distribution of the mainly genetically determined plasma Lp(a) levels are discussed. The main factors that can significantly change the inherited plasma Lp(a) levels are endocrine disorders and hormone treatment. It seems possible that sex hormones protect females to a large extent from the potentially deleterious effects of inherited high Lp(a) levels until menopause. The exceptionally strong independent association found in most studies between Lp(a) lipoprotein levels and atherosclerotic disorders indicates that Lp(a) is a factor of outstanding importance in the pathogenesis of atherosclerosis. Probable pathogenetic mechanisms are reviewed. The associations found between LP(a) and insulin release, rheumatoid arthritis and renal diseases suggest that Lp(a) may be involved in immunological mechanisms. In a new hypothesis it is suggested that an autoimmune process might especially occur in individuals with inherited high Lp(a) levels and certain HLA class II genotypes, triggered by a concurrent infection.


Occlusion of thoracic duct stent resulting in recurrent chyluria: role of renal-lymphatic fistula embolization.
Thoracic duct (TD) stenting is considered a treatment option for certain pathological conditions caused by TD obstruction, such as chyluria. Several studies have reported on the efficacy of TD stent treatment for both obstructive and leakage condition of TD, but few have evaluated the stent patency. This report aims to describe the patency of TD stent and the effectiveness of renal-lymphatic fistula embolization in the treatment of chyluria. We report a case of chyluria treated by TD stent previously, stent was placed at the TD venous junction four months before the symptoms recurred. At the second intervention we found the stent was obstructed by debris. We recanalized the stent and successfully catheterised the microcatheter through the stent retrograde into the TD then into the renal-lymphatic fistula branch. After embolization of that abnormal branch, the recurrent chyluria was treated and no further episode of chyluria was occurred during 12 months follow up. Stent in the TD may be occluded by debris. Embolization of renal-lymphatic fistula might be the most important treatment for spontaneous chyluria.


Monolayers of the lipid derivatives of isoniazid at the air/water interface and the formation of self-assembled nanostructures in water.
Isoniazid (INH, isonicotinic acid hydrazide) is one of the most commonly used anti-tubercular drugs. However, resistance of Mycobacterium tuberculosis strains to anti-mycobacterial agents including INH is an increasing problem worldwide. Development of new anti-mycobacterial agents thus has attracted attention. Five lipid derivatives of INH were prepared in this study. They formed monolayers at the air/water interface, and some nanostructures with different morphologies were obtained through molecular self-assembly in water. The derivatives included one fatty acyl derivative containing a 12-C hydrocarbon-long chain (1), three fatty alcohol derivatives with a succinyl as spacer and an 8, 12 or 16-C hydrocarbon-long chain (2, 3 and 4), and one tetrahydro-2H-1,3,5-thiadiazine-2-thione (THTT) derivative containing a 12-C hydrocarbon-long chain (5). The surface pressure-area isotherms depended on the volume and configuration of heads and the length of tails of derivatives. Compound 2 had a relatively large head and a short tail, easily standing uprightly at the interface. Under a certain surface pressure, the linear polar head groups of 3 could be partly squeezed out and insert into subphase because the length of heads were comparable to the one of tails. The very long tails of 4 always maintained above the interface and led to a high collapse pressure. Compound 5 possessed an extended and large head consisting of the THTT and INH groups so that the relatively short tails tilted at the interface and difficultly contact with each other. The THTT rings might be partly squeezed out and enter into air under a certain surface pressure. The self-assembly behaviours of derivatives in water depended on the molecular configuration and agreed with the corresponding monolayer behaviours. The flexible and medium-long tails (1 and 3) led to the derivatives to form nanoscale vesicles, though the short or very long tails did not (2 and 4). Interestingly, intermolecular hydrogen bonding could occur between the molecules of 5, and improve the derivative forming helical nanofibres other than vesicles. The molecular self-assembly of INH's lipid derivatives was explored in details in this study. The formation mechanisms of self-assembled nanostructures were analyzed. Various types of self-assembled nanostructures were obtained and the formation mechanisms were analyzed. The relationship between the self-assembly and the molecular configuration of amphiphilic derivatives was also revealed. The lipid derivatives of INH show promising anti-Mycobacterium action because the amphiphilic prodrugs allow for better penetration of the bacterial cells. The self-assembled nanostructures may likely be the potential self-assembled drug delivery systems for tuberculosis therapy.


A new fluorinated urethane dimethacrylate with carboxylic groups for use in dental adhesive compositions.
A urethane macromer containing hexafluoroisopropylidene, poly(ethylene oxide) and carboxylic moieties (UF-DMA) was synthesized and used in proportions varying between 15 and 35 wt.% (F1-F3) in dental adhesive formulations besides BisGMA, triethylene glycol dimethacrylate and 2-hydroxyethyl methacrylate. The FTIR and (1)H ((13)C) NMR spectra confirmed the chemical structure of the UF-DMA. The experimental adhesives were characterized with regard to the degree of conversion, water sorption/solubility, contact angle, diffusion coefficient, Vickers hardness, and morphology of the crosslinked networks and compared with the specimens containing 10 wt.% hydroxyapatite (HAP) or calcium phosphate (CaP). The conversion degree (after 180 s of irradiation with visible light) ranged from 59.5% (F1) to 74.8% (F3), whereas the water sorption was between 23.15 μg mm(-3) (F1) and 40.52 μg mm(-3) (F3). Upon the addition of HAP or CaP this parameter attained values of 37.82-49.14 μg mm(-3) (F1-F3-HAP) and 34.58-45.56 μg mm(-3), respectively. Also, the formation of resin tags through the infiltration of a dental composition (F3) was visualized by SEM analysis. The results suggest that UF-DMA taken as co-monomer in dental adhesives of acrylic type may provide improved properties in the moist environment of the mouth.


Increased noradrenaline release in rat portal vein during sympathetic nerve stimulation due to activation of presynaptic beta-adrenoceptors by noradrenaline and adrenaline.
With the aim of investigating whether exogenous noradrenaline (NA) and adrenaline (A) can modulate transmitter release via the stimulation of presynaptic beta-adrenoceptors, 3H-release from isolated portal veins was studied after pretreatment with 3H-1-NA, phenoxybenzamine, desipramine and normetanephrine. NA (10 muM) and A (0.05 muM) increased the fractional 3H-release elicited by sympathetic nerve stimulation by 30%. This effect could be blocked by d, 1-propranolol which per se reduced the release by 10%. It is concluded that NA can facilitate its own release via a presynaptic beta-adrenoceptor-mediated positive feed-back mechanism and that adrenaline can stimulate this beta-adrenoceptor-mediated mechanism.


Aggregated Amphiphilic Antimicrobial Peptides Embedded in Bacterial Membranes.
Molecular dynamics (MD) simulations, stochastic optical reconstruction microscopy (STORM), and neutron reflection (NR) were combined to explore how antimicrobial peptides (AMPs) can be designed to promote the formation of nanoaggregates in bacterial membranes and impose effective bactericidal actions. Changes in the hydrophobicity of the designed AMPs were found to have a strong influence on their bactericidal potency and cytotoxicity. G(IIKK)3I-NH2 (G3) achieved low minimum inhibition concentrations (MICs) and effective dynamic kills against both antibiotic-resistant and -susceptible bacteria. However, a G3 derivative with weaker hydrophobicity, KI(KKII)2I-NH2 (KI), exhibited considerably lower membrane-lytic activity. In contrast, the more hydrophobic G(ILKK)3L-NH2 (GL) peptide achieved MICs similar to those observed for G3 but with worsened hemolysis. Both the model membranes studied by Brewster angle microscopy, zeta potential measurements, and NR and the real bacterial membranes examined with direct STORM contained membrane-inserted peptide aggregates upon AMP exposure. These structural features were well supported by MD simulations. By revealing how AMPs self-assemble in microbial membranes, this work provides important insights into AMP mechanistic actions and allows further fine-tuning of antimicrobial potency and cytotoxicity.


Simulation of conformational changes in 2 Zn insulin.
Isolated insulin monomers, the dimer and higher aggregates from the 2 Zn crystal structure are subjected to convergent energy minimization in Cartesian co-ordinates using a force-field that includes the position of all hydrogen atoms. The minimizations are found, for the first time, to produce conformational changes of appreciable magnitude, which agree well with observed structural differences between monomers in the 2 Zn crystal and with the mechanism proposed previously for the coupling between deformations in different parts of the molecule. Our results also suggest that insulin would tend to adopt a molecule 1-like conformation in the absence of crystal packing forces, and that dimer formation is not at the origin of the observed asymmetry in the 2 Zn crystal.


Direct Aroylation of Olefins through a Cobalt/Photoredox-Catalyzed Decarboxylative and Dehydrogenative Coupling with α-Oxo Acids.
A photoredox/cobalt dual catalytic procedure has been developed that allows benzoylation of olefins. Here the photoredox catalyst effects the decarboxylation of α-ketoacids to form benzoyl radicals. After addition of this radical to styrenes, the cobalt catalyst abstracts a H-atom. Hydrogen evolution from the putative cobalt hydride intermediate allows a Heck-like aroylation without the need for a stoichiometric oxidant. Mechanistic studies reveal that electronically different styrenes lead to a curved Hammett plot, thus suggesting a change in product-determining step in the catalytic mechanism.


Mucociliary clearance in pulmonary vascular disease.
The mucociliary clearance function was studied by radioaerosol inhalation lung cinescintigraphy and its quantification in 8 patients with pulmonary vascular diseases; pulmonary embolism, 5 cases, and right pulmonary artery hypoplasia, pulmonary arteriovenous fistulas, aortitis syndrome, 1 case each. The mucociliary clearance function was found to be well maintained in pulmonary vascular diseases unless ventilation was disturbed. There was no difference in the mucociliary clearance function between pulmonary embolism and other pulmonary vascular diseases.


People with intellectual disabilities who are affected by a relative or friend with cancer: a qualitative study exploring experiences and support needs.
To explore the experiences of people with intellectual disabilities (ID) who have a relative or friend with cancer, and to identify their support needs. Participants were 21 adults with ID who had a relative/friend with cancer, now or in the past. Data were collected using focus groups and face-to-face interviews. Focus groups met four times, using a range of data collection techniques. Sessions were audio recorded and transcribed verbatim. Data were analysed using thematic content analysis. Data were collected between March 2010 and March 2011. Four themes emerged: (1) Protection and inclusion: participants who had not been told about their loved one's illness felt excluded; (2) Coping with cancer: participants had vivid memories of events and feelings. They worried about their families. Many had become carers themselves; (3) Understanding cancer: participants lacked knowledge about cancer and wanted to know more. (4) Someone to talk to: participants would have liked to share their feelings and questions with family, friends or professionals, but had not voiced their questions or concerns. 'Someone to talk to about my feelings and worries' and 'Someone to support the rest of my family' were voted the most helpful support strategies. Cancer nurses should ensure that people with ID in their patients' social circle are included in the family unit and receive adequate emotional support. They should be proactive in giving them information that is easy to understand. Using fictional stories can be particularly helpful in eliciting questions and concerns.


[Monoclonal antibodies in urology. Basic theories and clinical applications].
After briefly recalling the different lymphocytic populations and their interactions, the author describes the technique of producing human anticlonal bodies. He then goes on to analyze the implications of this new technology on kidney transplantation and genito-urinary oncology.


Mushroom-body memories: an obituary prematurely written?
Studies on insect olfactory learning have established the mushroom bodies as key brain structures for the formation of long-term memory (LTM). Two new neurons in the fly brain are reported now as essential sites for LTM formation, while mushroom bodies are claimed to be unnecessary to this end.


[Development of a training program for Japanese dyslexic children and its short-term efficacy].
The purpose of this study is to develop a computer training program of reading for the Japanese dyslexic children and to examine its short-term efficacy on their reading and writing abilities. Fifteen dyslexic children underwent two sets of training programs, one for single-hiragana and non-word reading, and the other for the reading of real words, in which each hiragana was followed by the correctly read sound. Subjects were required to use a given program for five minutes a day for three weeks, switching to the other program after a three-week interval. Four kinds of reading test and one writing test were done at the beginning and end of each program period. The averages reading speeds increased, and the single-hiragana reading error average was lower after the training. Hiragana-writing errors also decreased, even though no writing procedure was involved in the programs. The results indicate the usefulness of these training programs as an early intervention of reading and writing for the Japanese dyslexic children.


MicroRNA-223 triggers inflammation in porcine aorta by activating NLRP3 inflammasome under selenium deficiency.
Selenium (Se) is an essential trace element in organism. Se deficiency can cause many diseases, including vascular disease. Studies have shown that inflammation is the main inducement of vascular disease, microRNA (miRNA) can influence inflammation in various ways, and Se deficiency can affect miRNAs expression. To study the mechanism of aorta damage caused by Se deficiency, we constructed a Se deficiency porcine aorta model and found that Se deficiency can significantly inhibit miR-223, which downregulates the expression of nucleotide-binding oligomerization domain-like receptor family 3 (NLRP3). Subsequently, we found that in Se deficiency group, NLRP3, and its downstream (caspase-1, apoptosis-related spot-like protein [ASC], IL-18, IL-1β) expression was significantly increased. In vitro, we cultured pig iliac endothelium cell lines, and constructed miR-223 knockdown and overexpression models. NLRP3 messenger RNA and protein levels were significant increased in the knockdown group, and decreased in the overexpression group. The results of this study show that Se deficiency in porcine arteries can induce inflammation through miR-223/NLRP3.


Quality vaccines for all people: Report on the 16th annual general meeting of the Developing Countries Vaccine Manufacturers' Network, 05-07th October 2015, Bangkok, Thailand.
The Developing Countries Vaccine Manufacturers Network (DCVMN) assembled high-profile leaders from global health organisations and vaccine manufactures for its 16th Annual General Meeting to work towards a common goal: providing quality vaccines for all people. Vaccines contribute to a healthy community and robust health system; the Ebola outbreak has raised awareness of the threat and damage one single infectious disease can make, and it is clear that the world was not prepared. However, more research to better understand emerging infectious agents might lead to suitable vaccines which help prevent future outbreaks. DCVMN members presented their progress in developing novel vaccines against Dengue, HPV, Chikungunya, Cholera, cell-based influenza and other vaccines, demonstrating the commitment towards eliminating and eradicating preventable diseases worldwide through global collaboration and technology transfer. The successful introduction of novel Sabin-IPV and Oral Cholera vaccine in China and Korea respectively in 2015 was highlighted. In order to achieve global immunisation, local authorities and community leaders play an important role in the decision-making in vaccine introduction and uptake, based on the ability of vaccines to protect vaccinated people and protect non-vaccinated in the community through herd immunity. Reducing the risk of vaccine shortages can also be achieved by increasing regulatory convergence at regional and international levels. Combatting preventable diseases remains challenging, and collective efforts for improving multi-centre clinical trials, creating regional vaccine security strategies, fostering developing vaccine markets and procurement, and building trust in vaccines were discussed.


Glucocorticoids and their receptors: insights into specific roles in mitochondria.
Glucocorticoids (GCs) affect most physiological systems and are the most frequently used drugs for multiple disorders and organ transplantation. GC functions depend on a balance between circulating GC and cytoplasmic glucocorticoid receptor II (GR). Mitochondria individually enclose circular, double-stranded DNA that is expressed and replicated in response to nuclear-encoded factors imported from the cytoplasm. Fine-tuning and response to cellular demands should be coordinately regulated by the nucleus and mitochondria; thus mitochondrial-nuclear interaction is vital to optimal mitochondrial function. Elucidation of the direct and indirect effects of steroids, including GCs, on mitochondria is an important and emerging field of research. Mitochondria may also be under GC control because GRs are present in mitochondria, and glucocorticoid response elements (GREs) reside in the mitochondrial genome. Therefore, mitochondrial gene expression can be regulated by GCs via at least two different mechanisms: direct action on mitochondrial DNA and oxidative phosphorylation (OXPHOS) genes, or by an indirect effect through interaction with nuclear genes. In this review, we outline possible mechanisms of regulation of mitochondrial genes in response to GCs in view of translocation of the GR into mitochondria and the possible regulation of OXPHOS genes by GREs in the mitochondrial genome.


Cross-Cultural Adaptation and Psychometric Evaluation of Condom Use Self-Efficacy Scale in Chilean College Students.
Background and Purpose: Limited culturally relevant condom self-efficacy measures have been adapted for use with Chilean college students. This study aims to culturally adapt and measure the psychometric properties of the Condom Use Self-Efficacy Scale (CUSES) by use in college students in Chile. Methods: This cross-sectional study was carried out in six stages: (a) authorization from original authors, (b) translation, (c) back translation, (d) analysis of equivalences, (e) content analysis, and (f) exploratory factor analysis and reliability assessment. Results: Of the 460 college students who completed the Chilean CUSES (Ch-CUSES), 73.9% were women and 99% were single with a mean age of 20.5. Total scale Cronbach's alpha was 0.845, and factor analysis demonstrated six dimensions with 59.1% of the total variance. The factor loading scores of 21 items ranged between 0.515 and 0.921. Conclusions: Ch-CUSES shows good psychometric properties for assessing self-efficacy for condom use in Chilean college students.


Metabolism of metronidazole and antipyrine in isolated rat hepatocytes. Influence of sex and enzyme induction and inhibition.
The metabolism of metronidazole and antipyrine was investigated in freshly isolated hepatocytes from 7 male and 6 female control Wistar rats, 8 males and 5 females pretreated with phenobarbital (PB) and 3 males pretreated with 3-methylcholanthrene (MC). Pretreatment with PB increased the intrinsic clearance (CLi = Vmax/Km) of metronidazole to its acetic acid (MAA) and hydroxy metabolite (HM) 7- and 2.8-fold in the males and 3.2- and 3.0-fold in the females, whereas MC treatment increased the values 9- and 10-fold, respectively (P less than 0.05). The CLi of metronidazole to HM and its glucuronide conjugate was higher in the control and PB treated male than in the corresponding female groups, whereas the rank order was reversed for sulphate formation (P less than 0.05). SKF 525A was a more potent inhibitor of MAA formation than of HM formation, except in the PB treated male group. Pretreatment with MC increased the inhibitory potency of alpha-naphthoflavone and antipyrine toward MAA and HM formation. In male rats PB treatment increased the CLi of antipyrine to 3-hydroxymethyl-(HMAP), nor-(NORAP) and 4-hydroxyantipyrine (OHAP) 2.5-, 2.1- and 4.5-fold, respectively (P less than 0.05). Pretreatment with MC in male and with PB in female rats had no significant effect on antipyrine metabolism. SKF 525A was a more potent inhibitor of HMAP and OHAP formation than of NORAP formation. Treatment with MC increased the inhibitory potency of alpha-naphthoflavone toward the formation of all antipyrine metabolites. Metronidazole increased the formation rate of HMAP, but inhibited the formation of NORAP and OHAP, particularly the latter. The results suggest that the formation of MAA, HM, HMAP, NORAP and OHAP from metronidazole and antipyrine is catalyzed by different cytochrome P-450 isozymes, which may be supplemented or substituted by PB or MC induced species. The involved P-450 isozymes have more or less overlapping substrate and product specificity. Metronidazole appears to be a sensitive probe for detection and identification of PB and MC type induction.


[Resorbable antibiotic delivery systems in local treatment of chronic osteitis--polyglycolic acid/poly-L-lactide as drug carrier. Experimental studies in vitro].
Resorbable polyglycolic acid (PGA)- and poly-L-lactic acid (PLLA) cylinders were investigated in vitro to explore their properties as an antibiotic deposit (Ciprobay, Bayer Leverkusen) with prolonged release. PGA cylinders sized 3.2 x 5 mm, 4.5 x 5 mm and 4.5 x 7 mm respectively were shaped in monofil and polyfil technique. The Ciprofloxacin concentration varied from 0.5 mg to 5.0 mg of each cylinder. The cylinders were eluated in phosphate buffer, pH-value of 7.4, at 37 degrees C. The daily antibiotic release was measured by high performance liquid chromatography. Best combinations we could find demonstrated an initial delivery of Ciprofloxacin in vitro of 67 mg/l. The average daily release was about 16 mg/l during the first 36 days. After complete hydrolysis of the PGA carriers the recovery of Ciprofloxacin reached up to 6.5% and 11.6% respectively. For 40 bioactive cylinders (size phi 3.5 mm x 5 mm, containing 4 mg Ciprofloxacin) were eluated with phosphate buffer (pH 7.4 at 37 degrees C) respectively fresh human blood plasma and tested under various conditions. A gentamicin-polymethylmetacrylate (PMMA) chain (Septopal, E. Merck, Darmstadt) was exposed to equal test conditions for comparison. The quantities of released Ciprofloxacin and Gentamicin were analysed by a microbiological method (bioassay). Initially released rates of Ciprofloxacin were measured very high (up to 180 mg/l) but decreased rapidly within the first 5 days (4.2-22.5 mg/l). The release of Gentamicin produces an initial sharp decrease in concentration during the first 3 days (from 227.5 mg/l to 77.5 mg/l); this is then followed by an almost constant release over a long period of time (about 20 mg/l).(ABSTRACT TRUNCATED AT 250 WORDS)


Molecular detection of QTLs for agronomic and quality traits in a doubled haploid population derived from two Canadian wheats (Triticum aestivum L.).
Development of high-yielding wheat varieties with good end-use quality has always been a major concern for wheat breeders. To genetically dissect quantitative trait loci (QTLs) for yield-related traits such as grain yield, plant height, maturity, lodging, test weight and thousand-grain weight, and for quality traits such as grain and flour protein content, gluten strength as evaluated by mixograph and SDS sedimentation volume, an F1-derived doubled haploid (DH) population of 185 individuals was developed from a cross between a Canadian wheat variety "AC Karma" and a breeding line 87E03-S2B1. A genetic map was constructed based on 167 marker loci, consisting of 160 microsatellite loci, three HMW glutenin subunit loci: Glu-A1, Glu-B1 and Glu-D1, and four STS-PCR markers. Data for investigated traits were collected from three to four environments in Manitoba, Canada. QTL analyses were performed using composite interval mapping. A total of 50 QTLs were detected, 24 for agronomic traits and 26 for quality-related traits. Many QTLs for correlated traits were mapped in the same genomic regions forming QTL clusters. The largest QTL clusters, consisting of up to nine QTLs, were found on chromosomes 1D and 4D. HMW glutenin subunits at Glu-1 loci had the largest effect on breadmaking quality; however, other genomic regions also contributed genetically to breadmaking quality. QTLs detected in the present study are compared with other QTL analyses in wheat.


Prompt Predicting of Early Clinical Deterioration of Moderate-to-Severe COVID-19 Patients: Usefulness of a Combined Score Using IL-6 in a Preliminary Study.
The early identification of patients at risk of clinical deterioration is of interest considering the timeline of COVID-19 after the onset of symptoms. The aim of our study was to evaluate the usefulness of testing serum IL-6 and other serological and clinical biomarkers, to predict a short-term negative clinical course of patients with noncritical COVID-19. A total of 208 patients with noncritical COVID-19 pneumonia at admission were consecutively enrolled. Clinical and laboratory findings obtained on admission were analyzed by using survival analysis and stepwise logistic regression for variable selection. Three-day worsening as outcome in a logistic model to generate a prognostic score was used. Clinical worsening occurred in 63 patients (16 = died; 39 = transferred to intensive care unit; 8 worsening of respiratory failure). Forty-five of them worsened within 3 days after admission. The risk of clinical worsening was progressively enhanced along with increasing quartiles of IL-6 levels. Multivariate analysis showed that IL-6 (P = .005), C-reactive protein (CRP) (P = .003), and SaO2/FiO2 (P = .014) were the best predictors for clinical deterioration in the first 3 days after admission. The combined score yielded an area under the curve = 0.88 (95% confidence interval: 0.83-0.93). A nomogram predicting the probability of 3-day worsening was generated. The score also showed good performance for 7-day and 14- or 21-day worsening and in predicting death occurring during all the follow-up. Combining IL-6, CRP, and SaO2/FiO2 in a score may help clinicians to identify on admission those patients with COVID-19 who are at high risk for a further 3-day clinical deterioration.


Comparision of Mechanical Thrombectomy With Contact Aspiration or Stent Retriever in Patients With Large-vessel Occlusion in Acute Ischemic Stroke.
Whether the direct aspiration approach of thrombectomy for recanalization in patients with acute ischemic stroke has a similar efficacy and safety compared to the stent-retriever still remains uncertain. A retrospective data analysis was performed to identify patients with large cerebral artery acute ischemic stroke treated with endovascular thrombectomy. The study was conducted between January 2018 and December 2019 in a single stroke center. Twenty patients met inclusion criteria for this study with a mean age 66.64 ± 17.92 years' old. The symptom occurred on the left side were in 13, and the right side in 7. The location of occlusion was 8 in M1 of the middle cerebral artery of M2, and 6 in internal carotid artery. Nine patients were randomized to first-line treatment with contact aspiration and eleven to first-line treatment with a stent retriever. The mean time from admission time to groin puncture was 55.51 ± 31.03 minutes. The average time from groin puncture to maximal revascularizion after mechanical thrombectomy was 50.9 ± 22.5 minutes in contact aspiration group, but this time was 71.37 ± 25.45 minutes in the group of stent retriever. The overall successful revascularization rate (TICI 2b-3) was 88.9% in contact aspiration (TICI2a = 1, TICI 2b = 4 patients, TICI 3 = 4 patients), and 90.1% in stent retriever (TICI2a = 1, TICI 2b = 6 patients, TICI 3 = 4 patients). First-line thrombectomy with contact aspiration did not result in a higher successful revascularization rate at the end of the procedure but had a short time from groin puncture to maximal revascularizion.


Amplification of input differences by dynamic heterogeneity in the spiral ganglion.
A defining feature of type I primary auditory afferents that compose ∼95% of the spiral ganglion is their intrinsic electrophysiological heterogeneity. This diversity is evident both between and within unitary, rapid, and slow adaptation (UA, RA, and SA) classes indicative of specializations designed to shape sensory receptor input. But to what end? Our initial impulse is to expect the opposite: that auditory afferents fire uniformly to represent acoustic stimuli with accuracy and high fidelity. Yet this is clearly not the case. One explanation for this neural signaling strategy is to coordinate a system in which differences between input stimuli are amplified. If this is correct, then stimulus disparity enhancements within the primary afferents should be transmitted seamlessly into auditory processing pathways that utilize population coding for difference detection. Using sound localization as an example, one would expect to observe separately regulated differences in intensity level compared with timing or spectral cues within a graded tonotopic distribution. This possibility was evaluated by examining the neuromodulatory effects of cAMP on immature neurons with high excitability and slow membrane kinetics. We found that electrophysiological correlates of intensity and timing were indeed independently regulated and tonotopically distributed, depending on intracellular cAMP signaling level. These observations, therefore, are indicative of a system in which differences between signaling elements of individual stimulus attributes are systematically amplified according to auditory processing constraints. Thus, dynamic heterogeneity mediated by cAMP in the spiral ganglion has the potential to enhance the representations of stimulus input disparities transmitted into higher level difference detection circuitry.NEW & NOTEWORTHY Can changes in intracellular second messenger signaling within primary auditory afferents shift our perception of sound? Results presented herein lead to this conclusion. We found that intracellular cAMP signaling level systematically altered the kinetics and excitability of primary auditory afferents, exemplifying how dynamic heterogeneity can enhance differences between electrophysiological correlates of timing and intensity.


Brucella-related cerebral aneurysms/subarachnoidal hemorrhage: a short review featuring a case report.
Brucellosis is a multisystem disease that may present with a large spectrum of clinical manifestations. Only five cases of intracranial aneurysm formation and/or subarachnoidal hemorrhage associated with brucellosis have been reported. In this paper, we take the opportunity to review these reports and present a new case of basilar artery aneurysm and subarachnoidal hemorrhage due to brucellosis.


Accumulation of ornithine decarboxylase mRNA accompanies activation of human and mouse monocytes/macrophages.
Accumulation of ornithine decarboxylase (ODC) mRNA was investigated in human monocytes and mouse peritoneal macrophages. Treatment of both populations of mononuclear phagocytes with bacterial lipopolysaccharide induced a marked and rapid increase in the accumulation of the ODC gene transcript. A similar phenomenon, albeit less pronounced, was also observed following treatment of human monocytes with human recombinant interferon-gamma. These results suggest a role for ODC, and therefore polyamines, in the regulation of mononuclear phagocyte functions.


Dynamic volumetric hyperpolarized 13 C imaging with multi-echo EPI.
To generate dynamic, volumetric maps of hyperpolarized [1-13 C]pyruvate and its metabolic products in vivo. Maps of chemical species were generated with iterative least squares (IDEAL) reconstruction from multiecho echo-planar imaging (EPI) of phantoms of thermally polarized 13 C-labeled chemicals and mice injected with hyperpolarized [1-13 C]pyruvate on a preclinical 3T scanner. The quality of the IDEAL decomposition of single-shot and multishot phantom images was evaluated using quantitative results from a simple pulse-and-acquire sequence as the gold standard. Time course and area-under-the-curve plots were created to analyze the distribution of metabolites in vivo. Improved separation of chemical species by IDEAL, evaluated by the amount of residual signal measured for chemicals not present in the phantoms, was observed as the number of EPI shots was increased from one to four. Dynamic three-dimensional metabolite maps of [1-13 C]pyruvate,[1-13 C]pyruvatehydrate, [1-13 C]lactate, [1-13 C]bicarbonate, and [1-13 C]alanine generated by IDEAL from interleaved multishot multiecho EPI of live mice were used to construct time course and area-under-the-curve graphs for the heart, kidneys, and liver, which showed good agreement with previously published results. IDEAL decomposition of multishot multiecho 13C EPI images is a simple, yet robust method for generating high-quality dynamic volumetric maps of hyperpolarized [1-13 C]pyruvate and its products in vivo and has potential applications for the assessment of multiorgan metabolic phenomena.


Anastomotic failure complicating total gastrectomy and esophagogastrectomy for cancer of the stomach.
Anastomotic failure complicated the postoperative course of 11 per cent of 350 gastric cancer patients who underwent total gastrectomy and esophagogastrectomy and was responsible for 33 per cent of all operative deaths. The extent of disease and the presence of tumor at the margin of resection did not prove to be significant factors in regard to the incidence of anastomotic failure. Gastrectomy combined with resection of other organs was associated with a significantly higher risk of failure. End-to-end esophagogastrectomy and esophagoduodenostomy appeared to be prone to failure, while Roux-en Y, jejunal pouch, and jejunal loop reconstructions were safer. Patients with severe intraabdominal or intrathoracic sepsis had a poor prognosis, and their management with surgical or conservative methods was ineffective. On the basis of these findings, alternatives to manual methods of visceral suturing should be considered.


Atmospheric pollution problems and control proposals associated with solid waste management in China: a review.
Along with population growth, rapid urbanization and industrialization process, the volume of municipal solid waste (MSW) generation in China has been increasing sharply in the past 30 years and the total amount of MSW yields will continue to increase. Nowadays, due to global warming warrants particular attention throughout the world, a series of air pollutants (including greenhouse gases, odorous gases, PCDD/Fs, heavy metals, PM, etc.) discharged from waste disposal and treatment processes have become one of the new significant emerging air pollution sources, which arousing great concerns about their adverse effects on surrounding ambient air quality and public health. At present, the overall safely disposed ratio of the collected MSW in China is reported at approximately 78% in 2010, and there are mainly three types of MSW disposal methods practiced in China, including landfill, composting and incineration. The characteristics of air pollutants and greenhouse gases discharge vary substantially among different MSW disposal methods. By presenting a thorough review of MSW generation in China and providing a summarization of the current status of MSW disposal methods practices, this review article makes an integrated overview analysis of existing air pollution problems associated with MSW collection, separation, and disposal processes. Furthermore, some comprehensive control proposals to prevent air pollution for improving MSW management of China in the future are put forward.


Standardization and validation of assay of selected omega-3 and omega-6 fatty acids from phospholipid fraction of red cell membrane using gas chromatography with flame ionization detector.
Docosahexaenoic acid (DHA) is an important structural component of human brain and retina. Evidence exists linking nutritional status of pregnant mothers and cognitive functions of their born infants. The DHANI (Maternal DHA Supplementation and Offspring Neurodevelopment in India) trial was implemented to evaluate the effect of maternal supplementation with DHA during pregnancy and for 6 months following delivery on motor and mental development of infants at 1 and 12 months. We describe here the standardization and validation of an assay for measurement of selected omega-3 and omega-6 fatty acids from the phospholipid fraction of red blood cells to assess their status in mothers at baseline, delivery and 6 months post-delivery and for infants in cord blood and at 1 and 12 months of age. The validated method has been used for the analysis of samples for DHANI. Lipids were extracted from a pool of red blood cells, separated using thin layer chromatography. The phospholipid fraction was esterified, and fatty acids were separated by gas chromatography using a flame ionization detector. The method accuracy for DHA was between 97 - 98% and between 91 - 95% for arachidonic acid (AA) at three different concentrations. The intra-assay and inter-assay coefficient of variation for the fatty acids ranged from 1.19 to 5.7% and 0.78 to 13.0% respectively. Intraclass correlation (ICC), as a measure of reproducibility, ranged between 0.689 and 0.996. A good linearity was observed for all the fatty acids between concentrations of 0.2-4 μg/ml. The standardized and validated method is suitable for implementation in large epidemiological studies for evaluation of fatty acids and in nutritional trials for assessment of fatty acid content of various lipid classes.


1,25-Dihydroxyvitamin D3 analog structure-function assessment of the rapid stimulation of intestinal calcium absorption (transcaltachia).
The possibility is now emerging that 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] can mediate biologic responses via both genomic and nongenomic pathways. To understand the molecular basis of the nongenomic response of transcaltachia, defined as the 1,25-(OH)2D3-mediated rapid (2-10 minutes) stimulation of calcium transport from the brush border to the basal lateral membrane of the epithelial cell in vitamin D-replete chick intestine, and to address the issue of whether the same receptor for the secosteroid serves as the signal transducer for both genomic and nongenomic pathways, we carried out structure-function studies using seven analogs of 1,25-(OH)2D3 with different affinities for the classic nuclear 1,25-(OH)2D3 receptor as measured by determination in a steroid competition assay of the relative competitive index (RCI). The RCI of 1,25-(OH)2D3 is by definition 100. 1,25-(OH)2D3 initiates transcaltachia within 2-10 minutes of vascular perfusion and yields a biphase response curve. Dose-dependent stimulations of Ca2+ transport by the seven analogs indicates that different structural features are essential for initiating the transcaltachic response as contrasted with binding to the classic nuclear receptor. Vascular perfusion with analogs AT (25-OH-16-ene-23-yne-D3) and Y (25-OH-23-yne-D3), which are known to activate Ca2+ channels but bind very poorly to the classic receptor (RCI less than 0.5), are efficient in stimulating Ca2+ transport. By comparison, compounds BT [1 alpha,24S-(OH)2-22-en-26,27-dehydrovitamin D3] and V (1,25-(OH)2-16-ene-23-yne-D3], which bind very well to the classic nuclear receptor (RCI 75-111) but do not activate Ca2+ channels, are inefficient in stimulating Ca2+ transport. These results indicate that the membrane components that respond to the analogs of 1,25-(OH)2D3 with activation of Ca2+ channels have a different ligand specificity than the classic nuclear receptor.


Malignant adnexal tumor of the skin on breast: A case report of apocrine carcinoma.
Malignant adnexal tumors of the skin (MATS) are a group of rare and varied tumors that lack standardized guidelines for their management. Apocrine carcinoma (AC) is a highly uncommon form of breast malignancy, contributing to less than 1 % of all female invasive breast carcinomas. AC has a similar microscopic growth pattern to invasive ductal carcinoma, which can result in early misdiagnosis. This report presents a case of a 67-year-old female with a lump in the superior lateral quadrant of her left breast for six years. Surgical therapy was performed with wide excision due to clinical operability, no significant involvement of the axillary lymph nodes, and without metatasis. During the operation, Wide excision of 1-2 cm free margin according to standard and local reconstruction flaps were performed, with berry packing for the identified lymph nodes. The tumor was ER and PR negative, so hormonal treatment would be ineffective, assuming that this is an apocrine carcinoma of the breast. A metastatic work up was already done, and no metastasis was found. A mastectomy would appear to be a viable option. It is important to perform a clinical reevaluation to provide optimal treatment for breast malignancy. Misdiagnosis can occur early. In this case, a surgical procedure involving wide excision was performed, and as of now, the patient has not reported any recurrence.


Autoantibodies in paraneoplastic cerebellar degeneration bind to cytoplasmic antigens of Purkinje cells in humans, rats and mice and are of multiple immunoglobulin classes.
Purkinje cell autoantibodies in sera of six female patients with paraneoplastic cerebellar degeneration (PCD) were investigated by indirect immunofluorescence for immunoglobulin isotype and species specificity. Four patients had gynecologic cancer, one breast cancer and one lymphoma. Control sera from 125 patients were negative for Purkinje cell antibodies of IgG, IgM and IgA isotypes. These included neurologically normal cancer patients, cancer patients with paraneoplastic syndromes not involving the cerebellum and patients with non-neoplastic neurologic disorders. IgG antibodies in the six PCD sera bound to discrete cells in the cerebellum of human, rat and mouse (titers 1000-128,000). Antibodies of IgM class were additionally found in two sera (titers 100 and 500) and IgA in a third serum (titer 1000). Antibodies of each isotype gave a similar staining pattern, highlighting the cytoplasm of Purkinje cells in a coarse granular pattern, and the peripheral cytoplasm of discrete molecular layer cells. Antibodies of IgE class were not found. Rodent cerebellar tissue was found to be a useful substitute for human tissue in clinical testing for Purkinje cell antibodies, and has the advantage of being readily available in highly viable state. Its use should facilitate further characterization of the autoantigen(s) of PCD, and possibly the development of an animal model involving passive transfer of immunoglobulins. Screening for IgM and IgA Purkinje cell antibodies in addition to IgG may increase the yield of positive results in clinical serological testing.


Diabetes and hypoglycemia due to insulin antibodies.
A patient with "autoimmune diabetes" with reactive hypoglycemia due to anti-insulin antibodies is described. The pathophysiology of the impaired carbohydrate tolerance and reactive hypoglycemia is illustrated by measurements of C-peptide, and free and antibody-bound insulin. Detailed analysis of her antibodies did not provide any evidence in favor of exogenous insulin immunization. Nevertheless, a possible cause of unsuspected insulin immunization was present in her history which should be considered in other reported cases of "autoimmune diabetes" due to insulin antibodies in which exposure to insulin cannot be documented.


Myeloid cell-based therapies in neurological disorders: How far have we come?
The pathogenesis of neurological disorders such as multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD) is multifactorial and incompletely understood. The development of therapies for these disorders of the central nervous system (CNS) is thus far very challenging. Neuroinflammation is one of the processes that contribute to the pathogenesis of CNS diseases, and therefore represents an important therapeutic target. Myeloid cells derived from the bone marrow are ideal candidates for cell therapy in the CNS as they are capable of targeting the brain and providing neuroprotective and anti-inflammatory effects. In this review, experimental and clinical evidence for the therapeutic potential of myeloid cells in neurological disorders will be discussed. This article is part of a Special Issue entitled: Neuro Inflammation edited by Helga E. de Vries and Markus Schwaninger.


[HRCT and LDCT in workers exposed to asbestos: a review of the literature in view of the Helsinki Criteria].
In approaching the asbestos-related diseases with CT, both the malignant diseases and the non-malignant disease are to be considered. In the recent publication of the Helsinki Criteria research activities are encouraged in the field of lung cancer screening with low-dose CT (LDCT) in exposed workers and initiatives of data pooling and study protocols standardization are stimulated. Herein, we propose a review of the literature in the light of the Helsinki statement focused on the different techniques of imaging with CT and on the different fields of application in the asbestos-related disease.


Keratinization index.
A method to decrease subjectivity in assessing hyperkeratosis by application of quantitative measurements is proposed. The proportion of the depth of the stratum corneum to that of the total epidermis was measured on stained sections of tissue and termed the keratinization index (K.I.). Determinations showed that the K.I. varied with anatomical regions and was greater in different types of ichthyosis than in normal samples. Two indices were assessed, namely, K.I. which describes the ratio of cornified layer to total epidermis measured to the tips of the dermal papillae, and K.I. measured to the bases of the rete ridges. These two indices reflect the contour of the dermo-epidermal junction.


The role of serum and tissue pharmacology studies in the design and interpretation of chemoprevention trials.
The design and interpretation of chemoprevention trials are challenging tasks. Innovative methodological approaches to these investigations are in initial stages of development. Important pharmacologic issues should be addressed as early as possible in these trials to facilitate the optimal design of large, Phase III, randomized trials. These include determining the optimal dose of the compound and the toxicity profile. Other key areas involve the use of serum concentrations to monitor subject compliance, the evaluation of concentration of the chemopreventive agent in the target tissue, adequate assessment of the drug delivery systems, and the evaluation of the relationship between the dose administered and the serum or tissue concentrations achieved. Whenever possible the investigation of the relationship between serum or tissue concentrations of a chemopreventive agent vs its biologic activity should be determined. Specific examples involving the retinoids and carotenoids are presented.


The cancer chemotherapeutic 5-fluorouracil is a potent Fusobacterium nucleatum inhibitor and its activity is modified by intratumoral microbiota.
Fusobacterium nucleatum (Fn) is a dominant bacterial species in colorectal cancer (CRC) tissue that is associated with cancer progression and poorer patient prognosis. Following a small-molecule inhibitor screen of 1,846 bioactive compounds against a Fn CRC isolate, we find that 15% of inhibitors are antineoplastic agents including fluoropyrimidines. Validation of these findings reveals that 5-fluorouracil (5-FU), a first-line CRC chemotherapeutic, is a potent inhibitor of Fn CRC isolates. We also identify members of the intratumoral microbiota, including Escherichia coli, that are resistant to 5-FU. Further, CRC E. coli isolates can modify 5-FU and relieve 5-FU toxicity toward otherwise-sensitive Fn and human CRC epithelial cells. Lastly, we demonstrate that ex vivo patient CRC tumor microbiota undergo community disruption after 5-FU exposure and have the potential to deplete 5-FU levels, reducing local drug efficacy. Together, these observations argue for further investigation into the role of the CRC intratumoral microbiota in patient response to chemotherapy.


The excitation and depression of spinal neurones by ibotenic acid.
1. The firing of spinal interneurones and Renshaw cells by microelectrophoretic (+/-)-ibotenate, which was approximately eight times more active as an excitant than L-glutamate, was followed by prolonged depression of the sensitivity of the neurones to excitant amino acids and acetylcholine. 2. The depression, which lasted for 15--30 min when ibotenate was ejected for 3--6 min, was blocked by the GABA-antagonist bicuculline methochloride, and was independent of prior firing since it occurred with subthreshold concentrations of ibotenate and when ibotenate firing had been blocked by DL-alpha-aminoadipate. 3. When administered electrophoretically for 5 min, muscimol, a potent GABA agonist, reduced neuronal excitability for prolonged periods and this effect was also prevented by bicuculline methochloride. 4. The depression of neuronal excitability produced by GABA, taurine, isoguvacine or 3-aminopropane sulphonate, ejected for periods of 5--6 min, recovered rapidly. 5. It is suggested that ibotenate is converted in vivo to muscimol or a related compound which has a prolonged, bicuculline-sensitive depressant action on the excitability of neurones.


Morphometric aspects of the facial and skeletal muscles in fetuses.
There are few research reports providing a comparison of the muscle fiber morphometry between human fetuses and adults. Data on fetal and adult muscle fibers would be valuable in understanding muscle development and a variety of muscle diseases. This study investigated human muscle fiber growth to clarify the difference between the facial muscles and other skeletal muscles. The materials were obtained from three male fetuses (6-month-old) and 11 Japanese male cadavers aged 43-86 years (average: 71.8). Human buccinator muscles (facial muscles), masseter and biceps brachii muscles (skeletal muscles) were resected. We counted the muscle fibers and measured their transverse area. We also calculated the number of muscle fibers per mm(2) (NMF) and the average transverse area of the muscle fibers (TAMFs). The average of the NMF of the buccinator, masseter and biceps brachii muscles in fetuses had, respectively, 19, 37, and 22 times as many fibers as those in adults. The average fetus/adult ratios of the TAMF of the buccinator, masseter and biceps brachii muscles were 4.0%, 2.4%, 4.1%, respectively. The average NMF for all kinds of muscles decreased after birth; however, the peak in life-span or decreases with the aging process tended to vary with the kind of muscles examined. The average TAMF for all kinds of muscles enlarged after birth. We considered that the enlargement of the TAMF was connected with the emergence of fetal movements and functional demands after birth.


Role of the membrane in the inactivation of factor Va by activated protein C.
Bovine factor Va inactivation by activated protein C (APC) was evaluated in the presence and absence of phospholipid vesicles and protein S. Following a 30-min incubation with APC (10 nM), membrane-bound factor Va (200 nM) is completely inactivated, whereas in the absence of phospholipid vesicles, after a 2-h incubation, the cofactor retains 60% of its initial cofactor activity. The complete loss of activity of membrane-bound factor Va is associated with the appearance of M(r) 40,000, 28,000, and 20,000 fragments derived from the heavy chain of the cofactor which correspond to cleavage at Arg306, Arg505, and Arg662. In the absence of a lipid bilayer, cleavage at Arg505 and Arg662 results in a cofactor with reduced activity. No difference is observed in the cleavage of the light chain of the cofactor by APC in the presence or absence of phospholipid vesicles. The rate of the cleavage of factor Va heavy chain at Arg306, Arg505, and Arg662 as well as the rate of the membrane-bound cofactor inactivation by APC were enhanced in the presence of protein S. Our data demonstrate that the anionic lipid-dependent cleavage of factor Va by APC at Arg306 is required for the complete inactivation of the cofactor.


Double-blind placebo-controlled study of bepotastine besilate in pediatric patients with perennial allergic rhinitis.
Although second-generation antihistamines, such as bepotastine besilate, are recommended as a first-line treatment option for adult perennial allergic rhinitis (PAR), few non-sedating second-generation antihistamines are safe for children. A double-blind, placebo-controlled, comparative study of 473 pediatric PAR patients (7 - 15 years old) to determine the superiority and safety of bepotastine besilate (10 mg twice daily) relative to placebo for improved total and individual nasal symptom scores compared with baseline. Subjects were randomized to placebo (n = 233) or bepotastine besilate (n = 240, 10 mg orally twice daily for 2 weeks). Interference of daily life by PAR was assessed by measuring change in individual nasal symptom scores from baseline. Bepotastine besilate was superior to placebo in terms of total nasal symptom scores, with improved overall nasal symptoms of PAR compared with baseline values. Subgroup analyses demonstrated bepotastine besilate was effective irrespective of age, sex or body weight. No clinically significant adverse drug reactions often observed with first-generation antihistamines were reported and no difference in adverse events between groups was observed. Bepotastine besilate is effective and safe for pediatric PAR patients aged 7 - 15 years, and has a significant clinical impact on PAR. ClinicalTrials.gov identifier: NCT01861522 ( https://clinicaltrials.gov/ct2/show/NCT01861522 ).


Combined magnetic resonance coronary artery imaging, myocardial perfusion and late gadolinium enhancement in patients with suspected coronary artery disease.
Cardiovascular magnetic resonance (CMR) imaging offers methods for the detection of ischemia and myocardial infarction as well as visualization of the coronary arteries (MRCA). However, a direct comparison of adenosine perfusion (PERF), late gadolinium enhancement (LGE) and MRCA or the results of their combination has not been performed. Aim of the study was to evaluate the feasibility/diagnostic performance of rest/stress perfusion, late gadolinium enhancement and MRCA and their combination in patients with suspected coronary artery disease (CAD) in comparison to invasive angiography. Fifty-four patients (60 +/- 10 years, 35 men, CAD 48%) underwent CMR including MRCA (steady state free precession, navigator whole heart approach, spatial resolution 0.7 x 0.7 x .0.9 mm, trigger delay and temporal resolution adjusted individually), stress PERF (adenosine 140 mug/min/kg), rest PERF (SSFP, 3 short axis, 1 saturation prepulse per slice) and LGE (3D inversion recovery technique) using Gd-BOPTA. Images were analyzed visually. Stenosis >50% in invasive angiography was considered significant. Mean study time was 68 +/- 11 minutes. Sensitivity for PERF, LGE, MRCA and the combination of PERF/LGE and PERF/LGE/MRCA was 87%, 50%, 91%, 88% and 92%, respectively and specificity 88%, 96%, 46%, 88% and 56%, respectively. If image quality of MRCA was excellent (n = 18) the combination of MRCA/PERF/LGE yield a sensitivity of 86% and specificity of 91%. However, no test or combination improved diagnostic performance significantly compared to PERF alone. In patients with CAD, the combination of stress PERF, LGE and MRCA is feasible. When compared to invasive angiography, adenosine stress perfusion outperforms CMR coronary angiography in direct comparison and yields the best results with non-significant improvement in combination with LGE and significant deterioration in combination with MRCA. MRCA may be of additional value only in a minority of patients with excellent image quality.


Antibody response to P-protein in patients with Branhamella catarrhalis infections.
Branhamella catarrhalis is now recognized as an important cause of lower respiratory tract infections, especially in the elderly. In most instances, pathogenicity is presumed by recovery of the organism in a sputum culture, a method that is less than conclusive. In order to better diagnose B. catarrhalis infections, an enzyme-linked immunoassay has been developed using P-protein as antigen to measure antibodies to B. catarrhalis. In 17 elderly patients with B. catarrhalis pneumonia and 12 with tracheobronchitis, acute-phase serum antibody titers to P-protein were found to be significantly increased when compared with those of normal subjects (both p less than 0.02). There were no differences in antibody titers between patients with pneumonia and tracheobronchitis. Antibody titers of convalescent-phase sera increased over those of acute-phase sera in 46 percent of pneumonia patients and 50 percent of tracheobronchitis patients. The results demonstrated that lower respiratory tract infections with B. catarrhalis promote a significant elevation in antibody response to P-protein of B. catarrhalis.


Risk Prediction of Cardiovascular Complications in Pregnant Women With Heart Disease.
Heart disease in pregnancy is the leading cause of non- obstetric maternal death. Few Brazilian studies have assessed the impact of heart disease during pregnancy. To determine the risk factors associated with cardiovascular and neonatal complications. We evaluated 132 pregnant women with heart disease at a High-Risk Pregnancy outpatient clinic, from January 2005 to July 2010. Variables that could influence the maternal-fetal outcome were selected: age, parity, smoking, etiology and severity of the disease, previous cardiac complications, cyanosis, New York Heart Association (NYHA) functional class > II, left ventricular dysfunction/obstruction, arrhythmia, drug treatment change, time of prenatal care beginning and number of prenatal visits. The maternal-fetal risk index, Cardiac Disease in Pregnancy (CARPREG), was retrospectively calculated at the beginning of prenatal care, and patients were stratified in its three risk categories. Rheumatic heart disease was the most prevalent (62.12%). The most frequent complications were heart failure (11.36%) and arrhythmias (6.82%). Factors associated with cardiovascular complications on multivariate analysis were: drug treatment change (p = 0.009), previous cardiac complications (p = 0.013) and NYHA class III on the first prenatal visit (p = 0.041). The cardiovascular complication rates were 15.22% in CARPREG 0, 16.42% in CARPREG 1, and 42.11% in CARPREG > 1, differing from those estimated by the original index: 5%, 27% and 75%, respectively. This sample had 26.36% of prematurity. The cardiovascular complication risk factors in this population were drug treatment change, previous cardiac complications and NYHA class III at the beginning of prenatal care. The CARPREG index used in this sample composed mainly of patients with rheumatic heart disease overestimated the number of events in pregnant women classified as CARPREG 1 and > 1, and underestimated it in low-risk patients (CARPREG 0).


Achievements and challenges in baccalaureate student nurses' preparation for evidence-based nursing practice: A mixed methods study.
Evidence-based nursing (EBN) implementation is still limited. The effect of the incorporation of this competence into the whole nursing curricula as a cross-cutting topic has not yet been assessed. This study aimed to explore the perceptions of final year student nurses of their preparation for EBN practice and its current implementation in the local healthcare system. This study followed a mixed-methods approach. The data collection methods were a self-administered online questionnaire followed by individual in-depth interviews. The majority of participants (93.4%) chose asking a colleague as the main source of information for decision making during their last year of clinical training. However, scientific evidence was considered the most accurate and credible source instead of colleagues. The main barriers impeding EBN practice were revealed to be: not being able to find the required information, lack of time to search, and not feeling able to interpret information found. In the qualitative analysis of the interviews, three categories were identified: 'Towards EBN at a snail's pace'; 'A huge gap between theory and practice'; and 'Where is nursing?' Although participants in this study consistently attributed more credibility to clinical guidelines, protocols, and scientific publications over colleagues, asking a colleague continues to be the main resource to address clinical doubts. Lack of institutional support, the unresolved theory-practice gap in nursing, and the status of nurses in relation to other healthcare providers were identified as barriers for further EBN implementation.


Implementation of a Plan-Do-Study-Act framework to reduce unindicated surgical antimicrobial prophylaxis.
The goal of this study was to use a Plan-Do-Study-Act (PDSA) framework to reduce utilization of unindicated surgical antibiotic prophylaxis (SAP) for clean cases without foreign body implantation. This was a pre-post intervention study conducted at a single children's hospital comparing 6 months of retrospective preintervention data to 10 months of prospectively collected postintervention data. Interventions to reduce unindicated SAP included faculty meetings to review guidelines and establish consensus around inclusion criteria, publicizing guidelines with regular email reminders, and conducting ongoing compliance audits to root cause noncompliance. Early unanticipated noncompliant cases were associated with rotating trainees who prescribed SAP routinely without attending knowledge. A second PDSA cycle then included education-based emails targeting residents with mandatory feedback loop closure. Preintervention, 40.4% (107/265) of patients received unindicated SAP. Postintervention, the rate of unindicated SAP decreased to 15.4% (6/39) after the first month and 6.2% (20/323) after 10 months, reflecting an 85% reduction across periods (p < 0.01). There was no difference in the rate of surgical site infections between the pre and postintervention cohorts (0.36% vs. 0.67%, p = 1.00). Unindicated surgical antibiotic prophylaxis was significantly reduced by implementing a Plan-Do-Study-Act intervention targeting both faculty and trainees. Prospective comparative treatment study, level II.


Transmission electron microscopy studies in relation to production of solar cells from polycrystalline silicon sheets (R.A.D. process).
Ribbon against drop (R.A.D.) ribbons exhibit a polycrystalline texture similar to that of most melt-grown ribbons; we review here the defects of as-grown materials as well as after the solar cells' production.


Full Tensorial characterization of PZN-12%PT single crystal by resonant ultrasound spectroscopy.
An experimental setup based on the electrical excitation of a piezoelectric sample is proposed for resonant ultrasound spectroscopy measurements. The detection of the mechanical vibrations is performed by means of a laser interferometer. At the same time, the free vibrations of piezoelectric parallelepipeds of tetragonal and hexagonal symmetries are modeled taking into account the effect of the sample metalization. The paper presents the full elastic, piezoelectric and dielectric tensors of two PMN-34.5%PT ceramic and PZN-12%PT single crystal cubes.


Exposure to Metal Mixtures and Overweight or Obesity Among Chinese Adults.
Previous research has investigated the association between individual metal exposure and overweight/obesity (OW/OB). However, there is limited data about metal mixture exposure and OW/OB. This study aimed to explore the individual and joint effects of 21 metals on OW/OB and its metabolic phenotypes. A total of 4042 participants were enrolled in our study, and 51.0% of them were overweight/obese. We quantified 21 metal levels in the urine sample. OW/OB was defined as BMI ≥ 24 kg/m2, while the metabolic phenotypes, including metabolic unhealthy overweight/obesity (MUOW/OB) and metabolic health overweight/obesity (MHOW/OB), were determined by BMI and metabolic state. We used logistic regression to analyze the effect of individual metal exposure on OW/OB and its metabolic phenotypes. Quantile g-computation was applied to evaluate the joint effect of metal exposure on OW/OB and its metabolic phenotypes. In logistic regression, zinc (Zn) was positively associated with OW/OB, with the odds ratio (OR) in the highest quartiles of 2.19 (95% confidence interval (CI), 1.74, 2.77; P trend < 0.001), while arsenic (As) and cadmium (Cd) were negatively associated with OW/OB (OR = 0.70 (0.56, 0.87) and 0.61 (0.48, 0.78), respectively). After adjustment for age, gender, education, cigarette smoking, alcohol drinking, physical activity, meat intake, and vegetable intake, Zn was positively associated with MUOW/OB, while As, Cd, nickel (Ni), and strontium (Sr) were negatively associated with MUOW/OB (all P trend < 0.05). Quantile g-computation showed a significantly negative association between metal mixture exposure and MUOW/OB. Our study suggested that metal mixture exposure might be negatively associated with OW/OB, particularly with MUOW/OB. Zn, As and Cd contributed most to the effect of the mixture. More prospective studies are warranted to confirm these findings and reveal the underlying mechanisms.


[Study on the expression of the gene deleted in colorectal carcinoma in ovarian carcinoma].
The purpose of this study was to explore the relationship between the loss of the gene deleted in colorectal carcinoma (DCC) gene expression in ovarian carcinoma and the transformation, progression of the tumor and its clinicopathological factors. DCC gene mRNA expression were examined by reverse transcription polymerase chain reaction (RT-PCR) in 34 malignant, 10 benign and 10 normal ovarian samples. To clarify the expression of DCC gene by the DNA cloning and the DNA sequencing analysis in normal ovarian sample. The expression of DCC gene was lost in no normal ovarian tissues, in 2 (2/10) benign lesions, while the loss of DCC gene expression was found in 19 (19/34, 56%) carcinomas (P < 0.05). Similar findings were also noted when subdivision was into serous (14/18) and mucinous (4/11) categories (P < 0.05). The percentage of the loss of DCC gene expression in stage III - IV was 68%, in stage I - II was 22%, as well as 42% in grade I - II and 90% in grade III. 61% of the carcinoma with metastasis presented the loss of DCC gene expression, then there was 33% in which without metastasis. In ovarian carcinomas, loss of DCC gene expression was significantly related to the serous phenotype, a high histological grade and a more advanced stage. The results indicated that loss of DCC gene expression may play an important role in ovarian carcinomas and its progression.


Discovery and Optimization of a Series of Pyrimidine-Based Phosphodiesterase 10A (PDE10A) Inhibitors through Fragment Screening, Structure-Based Design, and Parallel Synthesis.
Screening of a fragment library for PDE10A inhibitors identified a low molecular weight pyrimidine hit with PDE10A Ki of 8700 nM and LE of 0.59. Initial optimization by catalog followed by iterative parallel synthesis guided by X-ray cocrystal structures resulted in rapid potency improvements with minimal loss of ligand efficiency. Compound 15 h, with PDE10A Ki of 8.2 pM, LE of 0.49, and >5000-fold selectivity over other PDEs, fully attenuates MK-801-induced hyperlocomotor activity after ip dosing.


Tumour necrosis factor activates the mitogen-activated protein kinases p38alpha and ERK in the synovial membrane in vivo.
Tumour necrosis factor (TNF) is considered to be a major factor in chronic synovial inflammation and is an inducer of mitogen-activated protein kinase (MAPK) signalling. In the present study we investigated the ability of TNF to activate MAPKs in the synovial membrane in vivo. We studied human TNF transgenic mice--an in vivo model of TNF-induced arthritis--to examine phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun amino terminal kinase (JNK) and p38MAPKalpha in the inflamed joints by means of immunoblot and immunohistochemistry. In addition, the effects of systemic blockade of TNF, IL-1 and receptor activator of nuclear factor-kappaB (RANK) ligand on the activation of MAPKs were assessed. In vivo, overexpression of TNF induced activation of p38MAPKalpha and ERK in the synovial membrane, whereas activation of JNK was less pronounced and rarely observed on immunohistochemical analysis. Activated p38MAPKalpha was predominantly found in synovial macrophages, whereas ERK activation was present in both synovial macrophages and fibroblasts. T and B lymphocytes did not exhibit major activation of any of the three MAPKs. Systemic blockade of TNF reduced activation of p38MAPKalpha and ERK, whereas inhibition of IL-1 only affected p38MAPKalpha and blockade of RANK ligand did not result in any decrease in MAPK activation in the synovial membrane. These data indicate that TNF preferentially activates p38MAPKalpha and ERK in synovial membrane exposed to TNF. This not only suggests that targeted inhibition of p38MAPKalpha and ERK is a feasible strategy for blocking TNF-mediated effects on joints, but it also shows that even currently available methods to block TNF effectively reduce activation of these two MAPKs.


Removal of acidic pharmaceuticals within a nitrifying recirculating biofilter.
The fate of pharmaceutically active compounds (PhACs) in wastewater treatment systems is an area of increasing concern. Little research has been done to understand this issue in rural or decentralized communities. The objective of this research was to examine the ability of a bench scale nitrifying recirculating biofilter (RBF) to remove four acidic PhACs: gemfibrozil, naproxen, ibuprofen and diclofenac from secondary treated municipal wastewater at concentrations of 20 and 200μg/L. The average removals in this study were between 92 and 99% for ibuprofen, 89 and 99% for naproxen, 62 and 92% for gemfibrozil and 40 and 76% for diclofenac, which is consistent with literature. Ibuprofen and naproxen were largely removed through biological transformation; whereas gemfibrozil and diclofenac showed more variable removal, likely due to both biological transformation and sorption processes. PhAC removal in the RBFs was repeatable between trials, robust and responsive to system upsets, and the presence of PhACs as a single compound versus mixtures had no impact on PhAC removal efficiency. In summary, this study indicates that RBFs as a nitrifying stage of a multi-stage filtration process could be a viable technology for removal of some acidic pharmaceuticals in small onsite wastewater treatment facilities.


Enhancement of the N-methyl-D-aspartate response in spinal dorsal horn neurons by cAMP-dependent protein kinase.
Glutamate-gated ion channels mediate excitatory synaptic transmission in the central nervous system and are involved in synaptic plasticity, neuronal development and excitotoxicity (5,24). These ionotropic glutamate receptors were classified according to their preferred agonists as AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid), KA (kainate), and NMDA (N-methyl-D-aspartate) receptors [Trends Pharmacol. Sci., 11 (1990) 25-33]. The present study of NMDA receptor channels expressed in acutely isolated spinal dorsal horn (DH) neurons of young rat reveals that they are subject to modulation through the adenylate cyclase cascade. Whole-cell voltage-clamp recording mode was used to examine the effect of adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase (PKA) on the responses of DH neurons to NMDA. Whole-cell current response to NMDA was enhanced by 8 Br-cAMP, a membrane permeant analog of cAMP or by intracellular application of cAMP or catalytic subunit of PKA.


High-Resolution Ultrasound Imaging of Axillary Nerve and Relevant Injury.
To evaluate the feasibility of axillary nerve (AN) visualization in healthy volunteers and the diagnostic value of AN injury via high-resolution ultrasonography (HRUS). AN was examined by HRUS on both sides of 48 healthy volunteers and oriented the transducer according to three anatomical landmarks: quadrilateral space, anterior to subscapular muscle, and posterior to axillary artery. The maximum short-axis diameter (SD) and cross-sectional area (CSA) of AN were measured at different levels, and AN visibility was graded by using a five-point scale. The patients suspected of having AN injury were assessed by HRUS, and the HRUS features of AN injury were observed. AN can be visualized on both sides in all volunteers. There was no significant difference in SD and CSA of AN at the three levels between the left and right sides or in SD between males and females. However, the CSA of males at different levels was slightly larger than those of females (P < .05). In most volunteers, AN visibility at different levels was excellent or good, and AN was best displayed anterior to subscapular muscle. Rank correlation analysis revealed that the degree of AN visibility had correlation with height, weight, and BMI. A total of 15 patients diagnosed with AN injury, 12 patients showed diffuse swelling or focal thickening in AN, and 3 patients showed AN discontinuity. HRUS is able to reliably visualize AN, and it could be considered as the first choice for diagnosing AN injury.


The influence of body mass index on thoracic injuries in frontal impacts.
For this study, a comprehensive analysis was performed to assess the influence of body mass index on thoracic injury potential. The data for this study were obtained from the National Automotive Sampling System-Crashworthiness Data System (NASS-CDS) database for years 1993-2005. Obese occupants had a 26 and 33% higher risk of AIS > or = 2 and AIS > or = 3 thoracic injury when compared to lean occupants. The increased risk of AIS > or = 3 injury due to obesity was slightly higher for older occupants, but the influence of age was greater than that of obesity. The increase in injury potential was higher for unbelted obese occupants than unbelted. Non-parametric and parametric risk curves were developed to estimate the risk of thoracic injury based on occupant BMI, belt use and delta-V. Overall, increase in thoracic injury risk due to obesity is more prominent in males and older occupants and for occupants sustaining AIS > or = 3 thoracic injuries.


Guar gum--its acceptability to diabetic patients when incorporated into baked food products.
Guar gum was incorporated into 10 g carbohydrate portions of cheese biscuits and 20 g carbohydrate portions of pizza and egg and bacon flan. Their acceptability to diabetic patients was assessed by means of a taste panel. The results were favourable. Other diabetic patients were asked to judge three cheese biscuits of varying guar gum content. The biscuit with the lowest content was most favoured.


Changes in health-related quality of life after carotid endarterectomy.
Carotid endarterectomy (CEA) is intended to prevent stroke and therefore to extend lifespan. Whether CEA also influences health-related quality of life (HRQOL) is largely unknown. This study aimed to assess HRQOL-changes after CEA. Prospective study, data assessment within 1 week before and 3 months after CEA. Patient classification (n = 70) was based on presenting neurological symptoms (none (24), transient (26), or permanent (20)), patency or occlusion (27%) of the contralateral internal carotid artery and intraoperative shunt requirement (28%). HRQOL was investigated with the Sickness Impact Profile (SIP). Analysis of variance was used to adjust for the influence of preoperative differences in functional impairment and comorbidity on the changes found. Preoperative findings showed that the SIP scores of stroke patients and shunted patients were significantly higher (indicating poorer HRQOL) than those of the other patients. No adverse effect of CEA was observed. Analysis of variance revealed that neurological classification was not reflected to HRQOL changes. However, patients with contralateral occlusion showed a significant postoperative improvement (f = 4.99, p < 0.05). HRQOL improvement after CEA is restricted to patients with occlusion of the contralateral carotid artery. Assessment of outcome of CEA should be related not only to neurological classification, but also to haemodynamic factors such as contralateral occlusion.


MiR-145 suppresses cell proliferation and motility by inhibiting ROCK1 in hepatocellular carcinoma.
MicroRNAs (miRNAs) play key roles in cancer development and progression. In the present study, we investigated the role of miR-145 in the progression of hepatocellular carcinoma (HCC). Ten HCC cell lines and samples from 96 patients with HCC were analyzed for the expression of miR-145 by quantitative real-time polymerase chain reaction (qRT-PCR). Overexpression of miR-145 was established by transfecting mimics into HepG2 and QGY-7703 cells. Cell proliferation and cell migration were assessed by cell viability assay and transwell assay. Western blot was to verify ROCK1 as a novel target gene of miR-145. Our results showed that miR-145 was frequently downregulated in HCC tumors and cell lines. Overexpression of miR-145 in HCC cell lines significantly inhibited cell proliferation, migration, and invasion in vitro. ROCK1 was identified as a target of miR-145, and ectopic expression of miR-145 downregulated ROCK1. Together, these findings indicate that miR-145 acts as a tumor suppressor and its downregulation in tumor tissues may contribute to the progression and metastasis of HCC through a mechanism involving ROCK1, suggesting miR-145 as a potential new diagnostic and therapeutic target for the treatment of HCC.


Expression and localization of the linear DNA plasmid-encoded protein (RS224) in Rhizoctonia solani AG2-2.
Expression of the linear DNA plasmid-encoded protein (RS224) from the plant-pathogenic fungus Rhizoctonia solani isolate H-16, anastomosis group 2-2, and its localization were studied. Extracts from Escherichia coli cells expressing the open reading frame (ORF) of RS224 (RS224ORF in pRS224) contain a 92-kDa T7.Tag-RS224orf fusion protein. Antisera raised against the fusion protein obtained from E. coli cells cross-reacted with a 90-kDa protein in the mycelia. To analyze the subcellular localization of the 92-kDa protein, mycelia of R. solani were disrupted and fractionated. Antibodies against RS224 proteins specifically reacted to the mitochondrial fraction, suggesting that RS224 is localized in mitochondria.


Increased production of ovarian thromboxane in gonadotropin-treated immature rats: relationship to the ovulatory process.
Thromboxane (TX) B2, a stable metabolic product of hydrolysis of TXA2, was measured by radioimmunoassay in tissue extracts of ovaries of immature rats pretreated with pregnant mare's serum gonadotropin and human chorionic gonadotropin. Ovarian concentrations of TXB2 increased before, and remained elevated after, the time of ovulation. In a subsequent study, ovulation was inhibited in a dose-dependent fashion by a reported TXA2 receptor antagonist, AH23848. Nevertheless, inhibition of the preovulatory rise in synthesis of TXB2 by furegrelate (a thromboxane synthetase inhibitor) did not prevent ovulation. Nor was the blockade of ovulation caused by indomethacin (a cyclooxygenase inhibitor) reversed by a TXA2 mimetic (U-46619). It does not appear that a preovulatory increase in ovarian thromboxane is an obligatory component of the ovulatory mechanism of gonadotropin-primed immature rats.


Preference of sheep for three forms of mucuna forage and the effect of supplementation with mucuna forage on the performance of sheep.
Assessment of the preference of sheep for fresh, dried or ensiled forms of mucuna (Mucuna pruriens var utilis) forage was followed by investigations into the effect of supplementing straw-based diets with the forage. Four sheep were offered fresh, dried and ensiled forms of the forage in a cafeteria style to assess their preference. In the second experiment, 20 sheep were randomly assigned to four dietary treatments, namely, alkali-treated straw only (M0), treated straw supplemented with mucuna forage at 0.3% (M10), 0.6% (M20) or 0.75% (M25) of body weight (approximately 10%, 20% and 25%, respectively, of the total dry matter intake). The daily feed intakes were determined and the sheep were weighed weekly for 10 weeks. The sheep showed a marked preference for fresh mucuna forage over either the dried or ensiled forms. The total dry matter intake increased by 15% and 21%, respectively, with M20 and M25. All the groups lost weight over the feeding period. However, only M0 gave weight losses during the second half of the feeding period. The feed conversion efficiency followed a trend similar to that for weight gains. M20 had the greatest effect on growth and feed conversion efficiency.


Maternal vitamin D status and child morbidity, anemia, and growth in human immunodeficiency virus-exposed children in Tanzania.
Vitamin D may help prevent adverse pediatric outcomes, including infectious diseases and growth failure, based on its role in immune and metabolic functions. We examined the association of maternal vitamin D status and pediatric health outcomes in children born to human immunodeficiency virus (HIV)-infected women. Vitamin D status was determined in 884 HIV-infected pregnant women at 12 to 27 weeks of gestation in a trial of vitamin supplementation (not excluding vitamin D) in Tanzania. Information on child morbidities, anemia and hypochromic microcytosis, and anthropometry was recorded through monthly clinic visits. Generalized estimating equations and Cox proportional hazards models were used to assess the relationships of outcomes with maternal vitamin D status. A total of 39% of women had low vitamin D levels (<32 ng/mL). Children born to women with low vitamin D status were 1.11 times more likely to report cough during follow-up (relative risk [RR], 1.11; 95% confidence interval [CI], 1.02-1.21). No significant associations were noted for other respiratory symptoms, diarrhea, or anemia outcomes. Low maternal vitamin D status was associated with significantly increased risk of stunting (height-for-age z score, <-2; RR, 1.29; 95% CI, 1.05-1.59) and being underweight (weight-for-age z score, <-2; RR, 1.33; 95% CI, 1.03-1.71). Maternal vitamin D status may be important for preventing respiratory infections and ensuring optimal growth in HIV-exposed children.


Small molecules enhance the potency of natural antimicrobial peptides.
The skin-associated microbiome plays an important role in general well-being and in a variety of treatable skin conditions. In this regard, endogenous antimicrobial peptides have both a direct and indirect role in determining the composition of the microbiota. We demonstrate here that certain small molecular species can amplify the antimicrobial potency of naturally occurring antimicrobial peptides. In this study, we have used niacinamide, a form of vitamin B3 naturally found in foods and widely used in cosmetic skincare products, and two of its structural analogs, to investigate their cooperativity with the human antimicrobial peptide LL37 on the bacterium Staphylococcus aureus. We observed a clear synergistic effect of niacinamide and, to some extent, N-methylnicotinamide, whereas isonicotinamide showed no significant cooperativity with LL37. Adaptively biased molecular dynamics simulations using simplified model membrane substrates and single peptides revealed that these molecules partition into the headgroup region of an anionic bilayer used to mimic the bacterial membrane. The simulated effects on the physical properties of the simulated model membrane are well correlated with experimental activity observed in real biological assays despite the simplicity of the model. In contrast, these molecules have little effect on zwitterionic bilayers that mimic a mammalian membrane. We conclude that niacinamide and N-methylnicotinamide can therefore potentiate the activity of host peptides by modulating the physical properties of the bacterial membrane, and to a lesser extent through direct interactions with the peptide. The level of cooperativity is strongly dependent on the detailed chemistry of the additive, suggesting an opportunity to fine-tune the behavior of host peptides.


Long-term efficacy of interferon therapy in patients with chronic hepatitis B virus infection in Japan.
Few studies have investigated the long-term effects of interferon (IFN) therapy for chronic hepatitis B (CHB). In this retrospective study, we investigated the efficacy of and predictors of response to IFN therapy in CHB patients. We analyzed data for 615 Japanese CHB patients (hepatitis B e antigen [HBeAg]-positive 414, HBeAg-negative 201) treated with IFN, and conducted follow up for a median duration of 8.1 years (range 0.5-23.2). Responders were defined as patients who showed continuously normalized alanine transaminase (ALT) levels, HBeAg clearance, and low hepatitis B virus (HBV) DNA levels at 6 months post-treatment or for a span of more than 6 months until each test point at 1, 3, 5, and 10 years. The IFN response rates of all patients were 21, 18, 21, 23, and 25% at 6 months and 1, 3, 5, and 10 years, respectively. On multivariate analysis, significant determinants of the outcome of IFN therapy were as follows: at 6 months and 1 year, young age, low HBV DNA levels, and long duration of treatment; at 3 years, long duration of treatment, young age, and high level of albumin; at 5 years, high level of albumin, female, and pretreated with IFN; and at 10 years, HBeAg-negative. Sixty-nine of the 615 patients (11%) achieved seroclearance of hepatitis B surface antigen (HBsAg). On multivariate analysis, age ≥30 years, HBV genotype A, and male were all independent factors predicting the achievement of HBsAg seroclearance. HBeAg, HBV DNA level, age, sex, albumin, duration of treatment, pretreatment with IFN, and HBV genotype were important factors in determining long-term response to IFN therapy.


A qualitative investigation of mental health promotion among aging gay men.
Background: Gay men, particularly middle aged and older men (over 40 years of age) experience a disproportionate burden of mental health issues compared to heterosexual men. Despite ample evidence that chronic exposure to structural and interpersonal discrimination negatively affect their mental health, little is known from gay men's perspectives how they understand mental health or their strategies to address their mental health concerns.Aim: This study's aim was to investigate how middle aged and older gay men experience their mental health and the mitigation strategies used to promote mental health.Method: Semi-structured interviews were conducted with 25 men who self-identified as gay. Data were analyzed using an interpretive descriptive approach.Results: Three overarching themes that best illustrate how men perceived their mental health and manage their mental health concerns were identified: gaining perspective, engaging with health services, and promoting and maintaining mental health.Conclusions: This study provides insight into how gay men come to acknowledge the validity of their mental health concerns, engage with health services, and their participation in other activities deemed essential for mental health promotion. These findings are ideally poised to inform development of health resources to promote and protect the mental health of aging gay men.


Audio-Visual Hallucinations in a Patient Poststem Cell Transplant.
Tramadol is the most common weak opioid used today. It has unique pharmacology and is notorious for numerous side effects as well as drug interactions. Patients undergoing stem cell transplant are susceptible to polypharmacy as a result of the generous use of antibiotics and symptom management drugs. Here, we describe a case where concurrent use of tramadol and fluconazole can cause hallucinations as a result of drug interaction.


Polymorphic variants at NDUFC2, encoding a mitochondrial complex I subunit, associate with cardiac hypertrophy in human hypertension.
A dysfunction of NADH dehydrogenase, the mitochondrial Complex I (CI), associated with the development of left ventricular hypertrophy (LVH) in previous experimental studies. A deficiency of Ndufc2 (subunit of CI) impairs CI activity causing severe mitochondrial dysfunction. The T allele at NDUFC2/rs11237379 variant associates with reduced gene expression and impaired mitochondrial function. The present study tested the association of both NDUFC2/rs11237379 and NDUFC2/rs641836 variants with LVH in hypertensive patients. In vitro studies explored the impact of reduced Ndufc2 expression in isolated cardiomyocytes. Two-hundred-forty-six subjects (147 male, 59.7%), with a mean age of 59 ± 15 years, were included for the genetic association analysis. Ndufc2 silencing was performed in both H9c2 and rat primary cardiomyocytes to explore the hypertrophy development and the underlying signaling pathway. The TT genotype at NDUFC2/rs11237379 associated with significantly reduced gene expression. Multivariate analysis revealed that patients carrying this genotype showed significant differences for septal thickness (p = 0.07), posterior wall thickness (p = 0.008), RWT (p = 0.021), LV mass/BSA (p = 0.03), compared to subjects carrying either CC or CT genotypes. Patients carrying the A allele at NDUFC2/rs641836 showed significant differences for septal thickness (p = 0.017), posterior wall thickness (p = 0.011), LV mass (p = 0.003), LV mass/BSA (p = 0.002) and LV mass/height2.7(p = 0.010) after adjustment for covariates. In-vitro, the Ndufc2 deficiency-dependent mitochondrial dysfunction caused cardiomyocyte hypertrophy, pointing to SIRT3-AMPK-AKT-MnSOD as a major underlying signaling pathway. We demonstrated for the first time a significant association of NDUFC2 variants with LVH in human hypertension and highlight a key role of Ndufc2 deficiency-dependent CI mitochondrial dysfunction on increased susceptibility to cardiac hypertrophy development.


Identification of N2-(1-carboxymethyl)guanine (CMG) as a guanine advanced glycation end product.
The reaction of D-glucose with 9-methylguanine produces N2-fructosyl-9-methylguanine, which undergoes oxidation to produce N2-(1-carboxymethyl)-9-methylguanine as a major adduct.


Myeloproliferative stem cell disorders by deregulated Rap1 activation in SPA-1-deficient mice.
SPA-1 (signal-induced proliferation-associated gene-1) is a principal Rap1 GTPase-activating protein in hematopoietic progenitors. SPA-1-deficient mice developed a spectrum of myeloid disorders that resembled human chronic myelogenous leukemia (CML) in chronic phase, CML in blast crisis, and myelodysplastic syndrome as well as anemia. Preleukemic SPA-1-deficient mice revealed selective expansion of marrow pluripotential hematopoietic progenitors, which showed abnormal Rap1GTP accumulation. Overexpression of an active form of Rap1 promoted the proliferation of normal hematopoietic progenitors, while SPA-1 overexpression markedly suppressed it. Furthermore, restoring SPA-1 gene in a SPA-1-deficient leukemic blast cell line resulted in the dissolution of Rap1GTP accumulation and concomitant loss of the leukemogenicity in vivo. These results unveiled a role of Rap1 in myeloproliferative stem cell disorders and a tumor suppressor function of SPA-1.


A Mental Health Innovation for Nurse Home Visiting Program Shows Effectiveness in Reducing Depressive Symptoms and Anxiety.
The objective of this paper is to report on the effectiveness of a mental health addition to a national nurse-delivered home visiting program. The methods are as follows: analysis of pre/post-launch of the standard Mental Health Intervention and comparison of 356 teams randomized to standard versus enhanced implementation. Stepwise regression controlled for significant client characteristics that were related to relevant outcomes. These characteristics were used in generalized mixed effect models comparing pre/post implementation and intervention and control groups. Pre/post analysis showed that only clients with no elevated mental health screening scores or mental health diagnoses at enrollment showed a significant decrease in depressive symptoms. Clients enrolled with and without mental health needs at enrollment significantly decreased on anxiety scores while referrals to mental health care increased. Teams receiving enhanced implementation enrolled more clients with mental health needs and clients completed more well-child visits and use of safe sleep practices. By integrating mental health care into maternal, infant, and early childhood home visiting programs, a new equitable model of primary mental health care can reach populations in need. This example provides a new paradigm of accessible and equitable mental health care for the future that can be implemented in a variety of home visiting programs.


[SDIALOR: a dialysis patient satisfaction questionnaire].
To develop and evaluate the psychometric properties of a dialysis satisfaction questionnaire in the French language. Firstly the translation and adaptation to French context in cooperation with dialysis patients and nephrologists. The satisfaction questionnaire was built using items banking, based on the Choice Satisfaction Questionnaire and Satisfaction of Patients in Chronic Dialysis (SEQUS((R))). The tool, named SDIALOR, was comprised of 41 items. Satisfaction scores are standardized from 0 (poor) to 100 (excellent). Secondly, the estimation of the questionnaire's psychometric properties. This work was realized in the Nephrolor network. The sample consisted in all of 1008 adults, prevalent patients, treated in the 12 dialysis structures of the Lorraine region on the 1st February 2004. All of them were mailed a questionnaire. Response rate was 44.3%. Mean age of patients was 65.9 years; 67% were men and 61% retired. Mean length of dialysis was 4.5 years. Women, residents of the Meurthe and Moselle region, patients having a diabetes, having a low haemoglobin level returned the questionnaires less frequently than the other patients (p<0.05). Principal components analysis evidenced seven specific dimensions, in addition to the overall satisfaction dimension. Cronbach's alpha coefficients were greater than 0.73 for five dimensions, but "relation between nephrologist and GP" dimension (0.54). Mean scores of satisfaction varied from 53.9 ("relation between nephrologists and GP") to 74.1 ("overall satisfaction"). Older patients tended to more satisfied than the younger ones. Global satisfaction was significantly higher in peritoneal dialyses (81.7), in hemodialysis at residence (83.1) compared with that in autodialyse (70.9) and in hemodialysis at center (73.3). A significant variability from one care team to another was evidenced. Our study proves the feasibility of satisfaction measurement at the dialyzed patient. Dialysis Patient Satisfaction Questionnaire in the French version exhibits satisfying psychometric properties. The level of satisfaction is better in peritoneal dialysis and differs according to medical care centers.


Detection of cellular micromotion by advanced signal processing.
Cellular micromotion-a tiny movement of cell membranes on the nm-µm scale-has been proposed as a pathway for inter-cellular signal transduction and as a label-free proxy signal to neural activity. Here we harness several recent approaches of signal processing to detect such micromotion in video recordings of unlabeled cells. Our survey includes spectral filtering of the video signal, matched filtering, as well as 1D and 3D convolutional neural networks acting on pixel-wise time-domain data and a whole recording respectively.