Synergistic Gas Hydrate and Corrosion Inhibition Using Maleic Anhydride: N-Isopropylmethacrylamide Copolymer and Small Thiols.
Kinetic gas hydrate inhibitors (KHIs) are often used in combination with film-forming corrosion inhibitors (CIs) in oilfield production flow lines. However, CIs can be antagonistic to KHI performance. In this study, maleic anhydride-co-N-isopropylmethacrylamide copolymer (MA:NIPMAM) and its derivatives were successfully synthesized and tested for gas hydrate and corrosion inhibition. KHI slow constant cooling (1 °C/h) screening tests in high-pressure rocking cells with synthetic natural gas and CO2 corrosion bubble tests in brine were performed in this study. The results revealed that underivatized MA:NIPMAM in water (as maleic acid:NIPMAM copolymer) showed poor KHI performance, probably due to internal hydrogen bonding. However, derivatization of MA:NIPMAM with 3-(dibutylamino)-1-propylamine (DBAPA) to give MA:NIPMAM-DBAPA gave excellent gas hydrate inhibition performance but only weak corrosion inhibition performance. Unlike some KHI polymers, MA:NIPMAM-DBAPA was compatible with a classic fatty acid imidazoline CI, such that neither the KHI polymer performance nor the corrosion inhibition of the imidazoline was affected. Furthermore, excellent dual gas hydrate and corrosion inhibition was also achieved in blends of MA:NIPMAM-DBAPA with small thiol-based molecules. In particular, the addition of butyl thioglycolate not only gave excellent corrosion inhibition efficiency, better than adding the fatty imidazoline, but also enhanced the overall gas hydrate inhibition performance.


Gastric and hepatic infarction following embolization of the left gastric artery: case report.
The authors report an initially successful left gastric artery embolization performed because of massive upper gastrointestinal bleeding; the procedure was complicated by focal gastric and hepatic infarctions. These complications occurred in the absence of underlying factors known to predispose to ischemia. Low-grade gastric bleeding persisting after seemingly successful embolization of the left gastric artery may indicate ischemic gastritis and is an indication for endoscopy. In addition, the presence of a left hepatic artery completely replaced to the left gastric artery should alert one to the potential for hepatic necrosis.


Vertical habitat stratification in Aedes triseriatus and Aedes hendersoni (Diptera: Culicidae): complications associated with sloped and flood-prone landscapes.
For the sibling mosquito species Aedes triseriatus Say and Ae. hendersoni Cockerell, success of offspring is highly dependent on oviposition site selection by gravid females, and the dynamics of that selection process have been the subject of much investigation. Patterns of vertical oviposition stratification were examined in this study by placing basal and canopy level oviposition traps in relatively steep and flat terrains, as well as in flood-prone riverbank vs upland settings. Strong stratification existed in both steep and flat terrains, with Ae. triseriatus favoring basal ovitraps and Ae. hendersoni favoring canopy ovitraps. Contrary to expectations, Ae. hendersoni displayed even more marked preference for canopy ovitraps in steeper terrain. Both species avoided basal ovitraps in flood-prone locations, where Ae. triseriatus oviposited only in canopy ovitraps and greatly outnumbered Ae. hendersoni in canopy ovitraps. In contrast, the expected stratification was found in nearby upland habitats.


[Triglyceride (TG) and remnant lipoproteins].
Lowering low-density lipoprotein (LDL) cholesterol (LDL-C) can reduce the risk of cardiovascular disease (CVD) by approximately 30%, and the remaining 70% should be the second front of CVD risk reduction. Such residual risks include high triglyceride (TG) concentrations and low levels of high-density lipoprotein (HDL) cholesterol (HDL-C) in terms of dyslipidemia. TG-rich lipoproteins are heterogenous and composed of a variety of subfractions, all of which are not necessarily relevant to atherosclerosis and CVD risk. However, remnant lipoproteins, TG-rich lipoproteins, are atherogenic and related to CVD risk. Two different methods (RLP-C and RemL-C) have been developed to measure cholesterol levels of remnant lipoproteins. Although there is a difference in affinity to intermediate-density lipoprotein (IDL) between the two methods, they may be better qualified as biomarkers of CVD risk than TG itself. TG measurements play a certain role in the evaluation of CVD risk, but the remnant lipoprotein cholesterol measurement can provide better screening for patients at high CVD risk than TG and may be a useful examination in both quantity and quality.


[Nursing as an evolving profession. Chaos and complexity theories applied to nursing tasks].
This article provides an idea how a nursing professional can make use of the Communicative-Evolutionary Model for in-depth analysis, the authors only concentrate on the relationship with patients and they illustrate what they propose by means of a vignette taken from a group of applications of the Communicative-Evolutionary Model for health personnel, applications which have had their sessions in Italy.


Does climate directly influence NPP globally?
The need for rigorous analyses of climate impacts has never been more crucial. Current textbooks state that climate directly influences ecosystem annual net primary productivity (NPP), emphasizing the urgent need to monitor the impacts of climate change. A recent paper challenged this consensus, arguing, based on an analysis of NPP for 1247 woody plant communities across global climate gradients, that temperature and precipitation have negligible direct effects on NPP and only perhaps have indirect effects by constraining total stand biomass (Mtot ) and stand age (a). The authors of that study concluded that the length of the growing season (lgs ) might have a minor influence on NPP, an effect they considered not to be directly related to climate. In this article, we describe flaws that affected that study's conclusions and present novel analyses to disentangle the effects of stand variables and climate in determining NPP. We re-analyzed the same database to partition the direct and indirect effects of climate on NPP, using three approaches: maximum-likelihood model selection, independent-effects analysis, and structural equation modeling. These new analyses showed that about half of the global variation in NPP could be explained by Mtot combined with climate variables and supported strong and direct influences of climate independently of Mtot , both for NPP and for net biomass change averaged across the known lifetime of the stands (ABC = average biomass change). We show that lgs is an important climate variable, intrinsically correlated with, and contributing to mean annual temperature and precipitation (Tann and Pann ), all important climatic drivers of NPP. Our analyses provide guidance for statistical and mechanistic analyses of climate drivers of ecosystem processes for predictive modeling and provide novel evidence supporting the strong, direct role of climate in determining vegetation productivity at the global scale.


Experiences of Middle-Aged and Older Taiwanese Adults With Chronic Insomnia: A Descriptive Qualitative Study.
The purpose of the current study was to describe the experiences of middle-aged and older adults with chronic insomnia. A descriptive qualitative study design was used, and semi-structured interviews were conducted with 17 participants from two primary clinic health centers in northern Taiwan. Mean age of participants was 64.3 years, most (58.8%) participants were middle aged (aged 40 to 64 years), and mean duration of insomnia was 5.6 years. Three themes emerged: Imperfection of Lived Experience, Dilemma of Whether to Take a Hypnotic, and Seeking Help from Alternative Therapy. Participants believed chronic insomnia contributed to an accumulation of anxiety and negative emotions, resulting in psychological burden. For participants with insomnia, because of their negative impressions of hypnotics, they usually sought alternative therapies to improve sleep. Health care providers should endeavor to understand the needs of individuals with insomnia and provide them with sleep hygiene knowledge and assistance in safe sleep practices. [Journal of Gerontological Nursing, 48(11), 21-28.].


Bacterial Root Microbiome of Plants Growing in Oil Sands Reclamation Covers.
Oil sands mining in northern Alberta impacts a large footprint, but the industry is committed to reclaim all disturbed land to an ecologically healthy state in response to environmental regulations. However, these newly reconstructed landscapes may be limited by several factors that include low soil nutrient levels and reduced microbial activity. Rhizosphere microorganisms colonize plant roots providing hosts with nutrients, stimulating growth, suppressing disease and increasing tolerance to abiotic stress. High-throughput sequencing techniques can be used to provide a detailed characterization of microbial community structure. This study used 16S rRNA amplicon sequencing to characterize the bacterial root microbiome associated with annual barley (Hordeum vulgare) and sweet clover (Melilotus albus) growing in an oil sands reclamation area. Our results indicate that Proteobacteria dominated the endosphere, whereas other phyla such as Acidobacteria and Gemmatimonadetes were restricted to the rhizosphere, suggesting that plants have the ability to select for certain soil bacterial consortia. The bacterial community in the endosphere compartments were less rich and diverse compared to the rhizosphere. Furthermore, it was apparent that sweet clover plants were more selective, as the community exhibited a lower richness and diversity compared to barley. Members of the family Rhizobiaceae, such as Sinorhizobium and Rhizobium were mainly associated with clover, whereas Acholeplasma (wall-less bacteria transmitted by insects) was unique to barley. Genera from the Enterobacteriaceae family, such as Yersinia and Lentzea were also mostly detected in barley, while other genera such Pseudomonas and Pantoea were able to successfully colonize both plants. Endophytic bacterial profiles varied within the same plant species at different sampling locations; however, these differences were driven by factors other than slope positions or cover management. Our results suggest that bacterial endophytic communities of plants growing in land reclamation systems are a subset of the rhizosphere community and selection is driven by plant factors.


Comparative characterization of the lactimidomycin and iso-migrastatin biosynthetic machineries revealing unusual features for acyltransferase-less type I polyketide synthases and providing an opportunity to engineer new analogues.
Lactimidomycin (LTM, 1) and iso-migrastatin (iso-MGS, 2) belong to the glutarimide-containing polyketide family of natural products. We previously cloned and characterized the mgs biosynthetic gene cluster from Streptomyces platensis NRRL 18993. The iso-MGS biosynthetic machinery featured an acyltransferase (AT)-less type I polyketide synthase (PKS) and three tailoring enzymes (MgsIJK). We now report cloning and characterization of the ltm biosynthetic gene cluster from Streptomyces amphibiosporus ATCC 53964, which consists of nine genes that encode an AT-less type I PKS (LtmBCDEFGHL) and one tailoring enzyme (LtmK). Inactivation of ltmE or ltmH afforded the mutant strain SB15001 or SB15002, respectively, that abolished the production of 1, as well as the three cometabolites 8,9-dihydro-LTM (14), 8,9-dihydro-8S-hydroxy-LTM (15), and 8,9-dihydro-9R-hydroxy-LTM (13). Inactivation of ltmK yielded the mutant strain SB15003 that abolished the production of 1, 13, and 15 but led to the accumulation of 14. Complementation of the ΔltmK mutation in SB15003 by expressing ltmK in trans restored the production of 1, as well as that of 13 and 15. These results support the model for 1 biosynthesis, featuring an AT-less type I PKS that synthesizes 14 as the nascent polyketide intermediate and a cytochrome P450 desaturase that converts 14 to 1, with 13 and 15 as minor cometabolites. Comparative analysis of the LTM and iso-MGS AT-less type I PKSs revealed several unusual features that deviate from those of the collinear type I PKS model. Exploitation of the tailoring enzymes for 1 and 2 biosynthesis afforded two analogues, 8,9-dihydro-8R-hydroxy-LTM (16) and 8,9-dihydro-8R-methoxy-LTM (17), that provided new insights into the structure-activity relationship of 1 and 2. While 12-membered macrolides, featuring a combination of a hydroxyl group at C-17 and a double bond at C-8 and C-9 as found in 1, exhibit the most potent activity, analogues with a single hydroxyl or methoxy group at C-8 or C-9 retain most of the activity whereas analogues with double substitutions at C-8 and C-9 lose significant activity.


Subtotal versus total parathyroidectomy with forearm autograft for secondary hyperparathyroidism in chronic renal failure.
Forty-three patients with chronic renal failure and secondary hyperparathyroidism underwent parathyroidectomy; 20 of the 43 underwent subtotal parathyroidectomy (Group A) and 23 patients underwent total parathyroidectomy and parathyroid autotransplant in the forearm (Group B). Postoperative clinical improvement was similar in both groups. In the immediate postoperative period eight patients in Group A who had severe bone changes and 21 patients in Group B needed supplemental calcium administration. The grafted tissues in all cases functioned well; reimplantation of the cryopreserved parathyroid tissues was unnecessary. One case in each group showed a recurrence. One patient in Group A was submitted to reexploration of the neck with a lateral approach. The other patient in Group B underwent excisions of the transplanted parathyroid tissues on three separate occasions under local anesthesia. The second operation was definitely easier and safer to manage after a total parathyroidectomy with autotransplantation to the forearm.


Isolation and characterization of a subgroup IIa WRKY transcription factor PtrWRKY40 from Populus trichocarpa.
Salicylic acid (SA) is a defense-related key signaling molecule involved in plant immunity. In this study, a subgroup IIa WRKY gene PtrWRKY40 was isolated from Populus trichocarpa, which displayed amino acid sequence similar to Arabidopsis AtWRKY40, AtWRKY18 and AtWRKY60. PtrWRKY40 transcripts accumulated significantly in response to SA, methyl jasmonate and hemibiotrophic fungus Dothiorella gregaria Sacc. Overexpression of PtrWRKY40 in transgenic poplar conferred higher susceptibility to D. gregaria infection. This susceptibility was coupled with reduced expression of SA-associated genes (PR1.1, PR2.1, PR5.9, CPR5 and SID2) and jasmonic acid (JA)-related gene JAZ8. Decreased accumulation of endogenous SA was observed in transgenic lines overexpressing PtrWRKY40 when compared with wild-type plants. However, constitutive expression of PtrWRKY40 in Arabidopsis thaliana displayed resistance to necrotrophic fungus Botrytis cinerea, and the expression of JA-defense-related genes such as PDF1.2, VSP2 and PR3 was remarkably increased in transgenic plants upon infection with fugal pathogens. Together, our findings indicate that PtrWRKY40 plays a negative role in resistance to hemibiotrophic fungi in poplar but functions as a positive regulator of resistance toward the necrotrophic fungi in Arabidopsis.


The supply of general practitioners across local areas: accounting for spatial heterogeneity.
The geographic distribution of general practitioners (GPs) remains persistently unequal in many countries despite notable increases in overall supply. This paper explores how the factors associated with the supply of general practitioners (GPs) are aligned with the arbitrary geographic boundaries imposed by the use of spatially referenced GP supply data. Data on GP supply in postcodes within Australia are matched to data on the population characteristics and levels of amenities in postcodes. Tobit regression models are used that examine the associations between GP supply and postcode characteristics, whilst accounting for spatial heterogeneity. The results demonstrate that GPs do not consider space in a one-dimensional sense. Location choice is related to both neighbourhood-specific factors, such as hospitals, and broader area factors, such as area income and proximity to private schools. Although the proportion of females and elderly were related to GPs supply, mortality rate was not. This paper represents the first attempt to map the factors influencing GP supply to the appropriate geographic level at which GPs may be considering that factor. We suggest that both neighbourhood and broader regional characteristics can influence GPs' locational choices. This finding is highly relevant to the design and evaluation of relocation incentive programmes.


Racial and socioeconomic disparities in sleep and chronic disease: results of a longitudinal investigation.
Sleep problems appear to differentially affect racial minorities and people of lower socioeconomic status (SES). These population subgroups also have higher rates of many debilitating diseases such as obesity, type 2 diabetes mellitus (T2DM), hypertension, coronary heart disease, stroke, and mortality. Considering the presence of social disparities in sleep and chronic disease, this research aims to assess the role of sleep disparities in the incidence of obesity, T2DM, hypertension, and/or cardiovascular disease (CVD). The Boston Area Community Health (BACH) Survey is a population-based random-sample cohort of 5502 participants aged 30-79. Sleep restriction (< or = 5 hours/night) and restless sleep were assessed at baseline. Health status was ascertained at baseline and approximately 5 years later among 1610 men and 2535 women who completed follow-up. Participants completed an in-person, home visit, interview at baseline (2002-2005) and follow-up (2006-2010). Boston, Massachusetts residents (2301 men, 3201 women) aged 30-79 years from three racial groups (1767 Black, 1876 Hispanic, 1859 White) participated in the BACH Survey. There were significant differences in the prevalence of sleep-related problems at baseline by both race and SES as well as significant disparities in the incidence of T2DM, high blood pressure and cardiovascular disease at follow-up. Restless sleep was associated with an increased risk of obesity, T2DM, and CVD. However, we found that sleep does not mediate social disparities in health outcomes. Results from the BACH Survey confirm large social disparities in health outcomes as well as large social disparities in short sleep duration and restless sleep. However, sleep did not appear to mediate the relationship between race, SES, and health disparities.


A black box mathematical model to calculate auto- and heterotrophic biomass yields based on Gibbs energy dissipation.
On the basis of the estimated Gibbs energy dissipation per C-mol biomass produced and a convenient black box description of microbial growth, a general equation for the calculation of the yield of biomass on electron donor has been obtained. This black box model defines four formal electron donating reactions for biomass, carbon source, electron donor, and electron acceptor. The proposed description leads to a simple equation which gives the biomass yield on electron donor for chemotrophic growth systems under carbon and energy limitation for which biomass is the only anabolic product. The variables involved are the degrees of reduction and the Gibbs energy characteristics of the four compounds, and the required Gibbs energy dissipation per C-mol produced of biomass. It appears that biomass yields on electron donor for auto- and heterotrophic growth under aerobic, denitrifying, and fermentative conditions can be estimated with 10-15% error in a range of Y(DX)-values of 0.01-0.80 C-mol/(C)-mol electron donor. Also, simple regularities in the Gibbs energy and enthalpy of organic substrates are found. Furthermore, simple relations are derived to calculate the thermodynamic maximal biomass yield, conditions required for growth to occur, heat production, biomass yield on electron acceptor, and anaerobic product yield. Finally a new definition of thermodynamic efficiency is derived.


Effect of Different Sampling Schedules on Results of Bioavailability and Bioequivalence Studies: Evaluation by Means of Monte Carlo Simulations.
Bioavailability and bioequivalence study is one of the most frequently performed investigations in clinical trials. Bioequivalence testing is based on the assumption that 2 drug products will be therapeutically equivalent when they are equivalent in the rate and extent to which the active drug ingredient or therapeutic moiety is absorbed and becomes available at the site of drug action. In recent years there has been a significant growth in published papers that use in silico studies based on mathematical simulations to analyze pharmacokinetic and pharmacodynamic properties of drugs, including bioavailability and bioequivalence aspects. The goal of this study is to evaluate the usefulness of in silico studies as a tool in the planning of bioequivalence, bioavailability and other pharmacokinetic assays, e.g., to determine an appropriate sampling schedule. Monte Carlo simulations were used to define adequate blood sampling schedules for a bioequivalence assay comparing 2 different formulations of cefadroxil oral suspensions. In silico bioequivalence studies comparing different formulation of cefadroxil oral suspensions using various sampling schedules were performed using models. An in vivo study was conducted to confirm in silico results. The results of in silico and in vivo bioequivalence studies demonstrated that schedules with fewer sampling times are as efficient as schedules with larger numbers of sampling times in the assessment of bioequivalence, but only if Tmax is included as a sampling time. It was also concluded that in silico studies are useful tools in the planning of bioequivalence, bioavailability and other pharmacokinetic in vivo assays.


Dual Recognition of Sialic Acid and αGal Epitopes by the VP8* Domains of the Bovine Rotavirus G6P[5] WC3 and of Its Mono-reassortant G4P[5] RotaTeq Vaccine Strains.
Group A rotaviruses, an important cause of severe diarrhea in children and young animals, initiate infection via interactions of the VP8* domain of the VP4 spike protein with cell surface sialic acids (SAs) or histo-blood group antigens (HBGAs). Although the bovine G6P[5] WC3 strain is an important animal pathogen and is also used in the bovine-human reassortant RotaTeq vaccine, the receptor(s) for the VP8* domain of WC3 and its reassortant strains have not yet been identified. In the present study, HBGA- and saliva-binding assays showed that both G6P[5] WC3 and mono-reassortant G4P[5] strains recognized the αGal HBGA. The infectivity of both P[5]-bearing strains was significantly reduced in αGal-free MA-104 cells by pretreatment with a broadly specific neuraminidase or by coincubation with the α2,6-linked SA-specific Sambucus nigra lectin, but not by the α2,3-linked specific sialidase or by Maackia amurensis lectin. Free NeuAc and the αGal trisaccharide also prevented the infectivity of both strains. This indicated that both P[5]-bearing strains utilize α2,6-linked SA as a ligand on MA104 cells. However, the two strains replicated in differentiated bovine small intestinal enteroids and in their human counterparts that lack α2,6-linked SA or αGal HBGA, suggesting that additional or alternative receptors such as integrins, hsp70, and tight-junction proteins bound directly to the VP5* domain can be used by the P[5]-bearing strains to initiate the infection of human cells. In addition, these data also suggested that P[5]-bearing strains have potential for cross-species transmission.IMPORTANCE Group A rotaviruses initiate infection through the binding of the VP8* domain of the VP4 protein to sialic acids (SAs) or histo-blood group antigens (HBGAs). Although the bovine G6P[5] WC3 strain is an important animal pathogen and is used as the backbone in the bovine-human reassortant RotaTeq vaccine, the receptor(s) for their P[5] VP8* domain has remained elusive. Using a variety of approaches, we demonstrated that the WC3 and bovine-human mono-reassortant G4P[5] vaccine strains recognize both α2,6-linked SA and αGal HBGA as ligands. Neither ligand is expressed on human small intestinal epithelial cells, explaining the absence of natural human infection by P[5]-bearing strains. However, we observed that the P[5]-bearing WC3 and G4P[5] RotaTeq vaccine strains could still infect human intestinal epithelial cells. Thus, the four P[5] RotaTeq vaccine strains potentially binding to additional alternative receptors may be efficient and effective in providing protection against severe rotavirus disease in human.


MicroRNA-362-3p Implicated in Cardioprotection Against Hypoxia/Reoxygenation-Induced Cardiomyocyte Apoptosis by Repressing TP53INP2 and Regulating SDF-1/CXCR4 Pathway.
To investigate the role of miR-362-3p and its target in cardiomyocytes with hypoxia/reoxygenation (H/R) injury. We found that miR-362-3p was decreased in myocardial infarction (MI) samples, and promoted the proliferation and restrained the apoptosis of H/R-injured H9c2 cells. TP53INP2 was recognized as the target of miR-362-3p and negatively modulated by miR-362-3p. Furthermore, the promotive effect of miR-362-3p on the proliferation of H/R-injured H9c2 cells was weakened by pcDNA3.1-TP53INP2, while the suppression on the apoptosis of H/R-injured H9c2 cells triggered by an miR-362-3p mimic was increased by pcDNA3.1-TP53INP2 by regulating apoptosis-associated proteins, as well as SDF-1 and CXCR4. miR-362-3p/TP53INP2 axis could ameliorate H/R-induced injury to cardiomyocytes by adjusting the SDF-1/CXCR4 signaling pathway.


Evaluating the Risk of Macrovascular Events and Mortality Among People With Multiple Sclerosis in England.
People with multiple sclerosis (MS) are associated with an increased risk of cardiovascular disease and mortality; however, evidence from population-based studies is sparse. To assess whether the risk of macrovascular events and mortality differs among people with MS compared with a matched population without MS in England. A population-based retrospective matched cohort study was conducted in general practices registered with the Clinical Practice Research Datalink in England between January 1, 1987, and September 30, 2018, with a mean (SD) follow-up of 11.3 (6.5) years. A total of 12 251 patients with MS were matched with up to 6 people without MS (n = 72 572) by age, sex, and general practice. People with 3 or more diagnoses of MS recorded during the study period were included. The first MS diagnosis was considered as index date. Multiple sclerosis status. Analyses were also stratified by sex. Main outcomes were acute coronary syndrome, cerebrovascular disease, any macrovascular disease (including peripheral arterial disease), and mortality (all-cause mortality and cardiovascular disease-specific mortality). Cox proportional hazards regression and Fine and Gray proportional subhazard regression models were used to assess differences in rates. A total of 12 251 people with MS (66.9% women; mean [SD] age, 44.9 [13.3] years) were matched with 72 572 people without MS (69.8% women; mean [SD] age, 44.9 [13.3] years). As compared with people without MS, people with MS were associated with a 28% increased hazard of acute coronary syndrome (hazard ratio [HR], 1.28; 95% CI, 1.09-1.51), 59% increased hazard of cerebrovascular disease (HR, 1.59; 95% CI, 1.32-1.92), 32% increased hazard of any macrovascular disease (HR, 1.32; 95% CI, 1.15-1.52), 3.5-fold increased hazard of all-cause mortality (HR, 3.46; 95% CI, 3.28-3.65), and 1.5-fold increased hazard in cardiovascular disease mortality (HR, 1.47; 95% CI, 1.27-1.71). Differences in macrovascular events were more pronounced among women than men. Mortality risk was also higher for women than men. Treatment with lipid-lowering medications (mainly statins) was associated with lower mortality rates among people with MS. This study suggests that MS is associated with an increased risk of cardiovascular and cerebrovascular disease that is not completely accounted for by traditional vascular risk factors. Given the adverse effects of these comorbidities on outcomes in patients with MS, further investigation is needed.


Self-mutilation in a child with a tethered spinal cord. Case report.
Self-mutilation after deafferentation injuries has rarely been reported in humans. The authors report on a 16-year-old girl who was born with a myelomeningocele. In adolescence it was noted that concurrent with her spinal cord becoming symptomatically tethered she began to self-mutilate her digits. A rare manifestation of the tethered spinal cord may be dysesthesias that led to self-mutilation.


Basal astrocyte and microglia activation in the central nervous system of Familial Hemiplegic Migraine Type I mice.
Gain-of-function missense mutations in the α1A subunit of neuronal CaV2.1 channels, which define Familial Hemiplegic Migraine Type 1 (FHM1), result in enhanced cortical glutamatergic transmission and a higher susceptibility to cortical spreading depolarization. It is now well established that neurons signal to surrounding glial cells, namely astrocytes and microglia, in the central nervous system, which in turn become activated and in pathological conditions can sustain neuroinflammation. We and others previously demonstrated an increased activation of pro-algogenic pathways, paralleled by augmented macrophage infiltration, in both isolated trigeminal ganglia and mixed trigeminal ganglion neuron-satellite glial cell cultures of FHM1 mutant mice. Hence, we hypothesize that astrocyte and microglia activation may occur in parallel in the central nervous system. We have evaluated signs of reactive glia in brains from naïve FHM1 mutant mice in comparison with wild type animals by immunohistochemistry and Western blotting. Here we show for the first time signs of reactive astrogliosis and microglia activation in the naïve FHM1 mutant mouse brain. Our data reinforce the involvement of glial cells in migraine, and suggest that modulating such activation may represent an innovative approach to reduce pathology.


The binding mechanism of eIF2β with its partner proteins, eIF5 and eIF2Bε.
The eukaryotic translation initiation factor eIF2 delivers Met-tRNAiMet to the ribosomal small subunit in GTP-bound form associated with eIF1, eIF1A, eIF3 and eIF5, and dissociates together with eIF5 as eIF5-eIF2-GDP complex from the ribosomal small subunit after formation of start codon-anticodon base pairing between Met-tRNAiMet and mRNA. The inactive form eIF2-GDP is then exchanged for the active form eIF2-GTP by eIF2B for further initiation cycle. Previous studies showed that the C-terminal domains of eIF5 (eIF5-CTD) and eIF2Bε (eIF2Bε-CTD) have a common eIF2β-binding site for interacting with an N-terminal region of eIF2β (eIF2β-NTD). Here we have reconstructed the complexes of (eIF5-CTD)-(eIF2β-NTD) and (eIF2Bε-CTD)-(eIF2β-NTD) in vitro, and investigated binding mechanism by circular dichroism spectroscopy and small angle X-ray scattering in solution. The results showed the conformation of eIF2β-NTD was changed when bound to partner proteins, whereas the structures of eIF5-CTD and eIF2Bε-CTD were similar in both isolated and complex states. We propose that eIF2β-NTD works as an intrinsically disordered domain which is disorder in the isolated state, but folds into a definite structure when bound to its partner proteins. Such flexibility of eIF2β-NTD is expected to be responsible for its binding capability.


Brain microstructural development in neonates with critical congenital heart disease: An atlas-based diffusion tensor imaging study.
Brain microstructural maturation progresses rapidly in the third trimester of gestation and first weeks of life, but typical microstructural development may be influenced by the presence of critical congenital heart disease (CHD). The aim of this study was to investigate the pattern of white matter (WM) microstructural development in neonates with different types of critical CHD. The secondary aim was to examine whether there is an association between WM microstructural maturity and neonatal ischemic brain injury. For this prospective, longitudinal cohort study, 74 term born neonates underwent diffusion tensor imaging (DTI) before (N = 56) and after (N = 71) cardiac surgery performed <30 days of life for transposition of the great arteries (TGA), single ventricle physiology with aortic arch obstruction (SVP-AO), left- (LVOTO) or right ventricle outflow tract obstruction (RVOTO). Microstructural integrity was investigated by fractional anisotropy (FA) and by mean diffusivity (MD) in 16 white matter (WM) structures in three WM regions with correction for postmenstrual age. Ischemic brain injury was defined as moderate-severe white matter injury or stroke. Before cardiac surgery, the posterior parts of the corona radiata and internal capsule showed significantly higher FA and lower MD compared to the anterior parts. Centrally-located WM structures demonstrated higher FA compared to peripherally-located structures. Neonates with TGA had higher FA in projection-, association- and commissural WM before surgery, when compared to other CHD groups. Neonates with LVOTO showed lower preoperative MD in these regions, and neonates with SVP-AO higher MD. Differences in FA/MD between CHD groups were most clear in centrally located WM structures. Between CHD groups, no differences in postoperative FA/MD or in change from pre- to postoperative FA/MD were seen. Neonatal ischemic brain injury was not associated with pre- or postoperative FA/MD. Collectively, these findings revealed brain microstructural WM development to follow the same organized pattern in critical CHD as reported in healthy and preterm neonates, from posterior-to-anterior and central-to-peripheral. Neonates with TGA and LVOTO showed the most mature WM microstructure before surgery and SVP-AO the least mature. Degree of WM microstructural immaturity was not associated with ischemic brain injury.


Testing hypothesized predictors of change in conjoint behavioral alcoholism treatment for men.
The model on which alcohol-related Behavioral Couples Therapy (ABCT) is based posits three primary domains related to alcohol consumption: individual factors, the quality and nature of the spouse's response to alcohol-related situations, and the nature and quality of the couple's marital interactions. This study tested the model underlying ABCT in a sample of 68 male alcoholics and their partners, who completed at least five sessions of a 15-session outpatient treatment study in which they received ABCT. Couples were assessed at baseline, during treatment, and for 6 months after treatment completion. Stepwise multiple regression was used to test specific predictors derived from the ABCT model. Some support was provided for each component of the ABCT model. Individual drinker variables predicted drinking outcomes, both during and after treatment. Specifically, greater drinking severity and drinking frequency at baseline predicted poorer drinking outcomes. Older client age and more education predicted less frequent but more intense drinking. Spouse coping was related primarily to measures of drinking intensity, rather than drinking frequency. Less intense drinking during treatment was predicted by greater spousal use of problem solving and social support to deal with problems and less use of self-blame, wishful thinking, and avoidance. After treatment, however, spouse coping had a less consistent relationship to drinking intensity. In the marital domain, drinking during treatment was unrelated to pretreatment marital satisfaction measures. However, in the 6 months after treatment, men's ability to remain abstinent was predicted by the quality of the pretreatment marital relationship, and the intensity of their drinking was predicted by the degree of their marital happiness immediately after treatment. Results provided substantial support for the ABCT model, particularly in relationship to the role of the spouse in affecting heavy drinking.


The quality of osteolysis grafting with cementless acetabular component retention.
Periprosthetic osteolysis is a common cause for revision of total hip arthroplasty. When modular cementless acetabular components are stable, curettage and grafting of the osteo-lytic lesion while retaining the component are a good surgical option. Although the midterm outcome of this procedure is known, the quality of the surgical technique is not. We used preoperative and postoperative computed tomography to determine the percentage of periacetabular lesions that was grafted and the percentage of the lesion volume filled with an injectable bone graft substitute. We discovered, even with preoperative computed tomography reconstructions and surgical planning, four of 22 lesions were neglected at the time of surgery. In the 18 lesions that were treated, we were able to fill an average of 49% (range, 0-83%) of the lesion volume. These inconsistent results illustrate a need to further refine surgical techniques and instrumentation to treat one of the most common complications in total hip arthroplasty. Longer followup with repeat computed tomography scans or other imaging techniques would determine if the percentage of lesion fill has an effect on clinical outcome.


Serum iron and neuroleptic malignant syndrome.
Neuroleptic malignant syndrome (NMS) is a fulminant, life-threatening reaction to neuroleptic medications. The only consistently described biochemical abnormalities are increased creatine kinase and leucocytosis. Because of a possible association between NMS and dopaminergic function and between serum iron and dopaminergic function, we prospectively measured serum iron in 26 episodes of NMS in twenty-three patients. In 25 episodes (96%) serum iron concentration was 10 mumol/l or lower--more than 2 SD below the mean normal value. Serum iron in 11 episodes (36%) was 4 mumol/l or lower. In each episode for which data are available, serum iron returned to normal upon resolution of the NMS. Serum iron may be a helpful adjunct for the diagnosis of the disorder. The pronounced reduction in serum iron suggests that the acute phase reaction may have a role in NMS.


The mycoremediation potential of the armillarioids: a comparative genomics analysis.
Genes involved in mycoremediation were identified by comparative genomics analysis in 10 armillarioid species and selected groups of white-rot Basidiomycota (14) and soft-rot Ascomycota (12) species to confine the distinctive bioremediation capabilities of the armillarioids. The genomes were explored using phylogenetic principal component analysis (pPCA), searching for genes already documented in a biocatalysis/biodegradation database. The results underlined a distinct, increased potential of aromatics-degrading genes/enzymes in armillarioids, with particular emphasis on a high copy number and diverse spectrum of benzoate 4-monooxygenase [EC:184.108.40.206] homologs. In addition, other enzymes involved in the degradation of various monocyclic aromatics were more abundant in the armillarioids than in the other white-rot basidiomycetes, and enzymes involved in the degradation of polycyclic aromatic hydrocarbons (PAHs) were more prevailing in armillarioids and other white-rot species than in soft-rot Ascomycetes. Transcriptome profiling of A. ostoyae and A. borealis isolates confirmed that several genes involved in the degradation of benzoates and other monocyclic aromatics were distinctively expressed in the wood-invading fungal mycelia. Data were consistent with armillarioid species offering a more powerful potential in degrading aromatics. Our results provide a reliable, practical solution for screening the likely fungal candidates for their full biodegradation potential, applicability, and possible specialization based on their genomics data.


Multiple molecular forms of rat liver pantothenate kinase.
Pantothate kinase (E.C.188.8.131.52) was partially purified from rat liver and analyzed by preparative isoelectric focusing and cation-exchange high performance liquid chromatography. Two main peaks of catalytic activity were found in the focusing gel at isoelectric point of 5.7 (peak A) and 5.1 (peak B). Two major molecular forms of the enzyme was also demonstrated by high performance liquid chromatography. Both molecular forms of the enzyme were inhibited by 0.02 mmol/l CoASH and acetyl-CoA. CoA at 0.02 mmol/l inhibited the isoenzyme peak B only slightly (6%) compared to the isoenzyme peak A (80%). Acetyl-CoA at 0.02 mmol/l inhibited peak A and B with about equal strength (96% and 83% respectively). The relative amounts of these two molecular forms of pantothenate kinase in different organs might contribute to the regulation of CoA synthesis in mammalian cells.


[Effect of Water Intake on Allergy-like Events Associated with Non-ionic Iodine Contrast Agents].
The use of iodine contrast agents occasionally causes serious allergic symptoms including anaphylaxis. At Kyoto University Hospital to prevent nephropathy we began recommending water intake before and after administration of iodine contrast agents in September 2012. In the present study we investigated the effect of water intake on the incidence of allergy-like events after the use of non-ionic iodine contrast agents. We extracted the occurrence of allergy-like events from the incident report system in our hospital from January 2011 to September 2014, and classified these events into the following 3 grades: 1+ (follow-up); 2+ (medication treatment); and 3+ (hospitalization). The allergy-like incidence rate was calculated for subsequent evaluation according to season and water intake. Allergy-like events significantly decreased from 0.49% before the recommendation of water intake to 0.26% at 1 year and 0.20% at 2 years after implementing the recommendation. The incidence of allergy-like events was significantly higher in summer than in winter before water intake was recommended. After implementing the recommendation, the value for summer significantly decreased to an incidence similar to that of winter. Respiratory and gastrointestinal allergy-like symptoms were dramatically decreased after implementing the recommendation. Water intake may be useful for preventing allergy-like events associated with non-ionic iodine contrast agents, especially during the summer.


Pain assessment in the recovery room.
The assessment and management of pain in the acute hospital setting is an important issue for practitioners (Layman Young et al 2005). Despite advances in pain management (Fotiadis et al 2004, Powell et al 2004, Wu & Richman 2004) and the use of multimodal analgesic techniques in the theatre/recovery environment (Jin & Chung 2001), for a variety of reasons (Turk & Okifuji 1999, Pasero 2003), patients' reports of pain following surgery suggest that it remains problematic (Rawal 2002, Brown 2004, Coll et al 2004). In the recovery room disorientation, anxiety, fear and nausea may add to and alter patients' perception of pain, making it crucial that recovery room practitioners understand pain and pain assessment. This article outlines and critiques pain assessment tools that may be used to enhance pain management practices in the recovery room.


A continuing challenge: N-heterocyclic carbene-catalyzed syntheses of γ-butyrolactones.
Catalytic, stereoselective N-heterocyclic carbene-catalyzed reactions facilitate efficient construction of many different heterocyclic compounds, such as the enantioenriched 5-membered (γ) lactones highlighted in this tutorial review. Herein, various strategies to enable formal [3+2] type annulations between electrophilic carbonyl equivalents and homoenolate nucleophiles for the synthesis of γ-lactones are summarized.


The Correlation Analysis between Corneal Biomechanical Properties and the Surgically Induced Corneal High-Order Aberrations after Small Incision Lenticule Extraction and Femtosecond Laser In Situ Keratomileusis.
Background. To investigate the correlation between corneal biomechanics and the surgically induced corneal high-order aberrations (HOAs) after small incision lenticule extraction (SMILE) and femtosecond laser in situ keratomileusis (FS-LASIK). Methods. A total of 150 right myopic eyes that underwent SMILE or FS-LASIK surgery were included in this retrospective study, 75 eyes in each group. The corneal hysteresis (CH) and the corneal resistance factor (CRF) with the corneal HOAs of the anterior, posterior, and total cornea were assessed preoperatively and three months postoperatively. Multivariate linear regression was applied to determine the correlations. Results. The preoperative CRF was significantly correlated with the induced 3rd-6th-order HOAs and spherical aberration of the anterior surface and the total cornea after SMILE and FS-LASIK surgeries (P < 0.05), postoperatively. The CRF was significantly correlated with the induced vertical coma of the anterior and posterior surfaces and the total cornea after SMILE surgery (P < 0.05). There was a significant correlation between the CRF and the induced posterior corneal horizontal coma after FS-LASIK surgery (P = 0.013). Conclusions. The corneal biomechanics affect the surgically induced corneal HOAs after SMILE and FS-LASIK surgery, which may be meaningful for screening the patients preoperatively and optimizing the visual qualities postoperatively.


Development of an active intravascular MR device with an optical transmission system.
Magnetic resonance imaging (MRI) is a safe and reliable medical imaging method providing good soft tissue contrast while avoiding harmful ionizing radiation. It is highly desirable to use the MRI technology for interventional procedures. However, due to resonance effects that can result in tissue heating, long conducting cables must be avoided. Motivated by the need for more radio-frequency (RF) safety, we developed an optical transmission system for active intravascular MRI devices. An optical transmitter sends the MR signal via an optical fiber. A miniature optical modulator was designed to be integrated into a catheter tip. Furthermore, power is supplied optically to the transmitter. This system can target new medical applications, due to safe catheter tracking and safe intravascular imaging.


Multi-Faceted Role of Melatonin in Neuroprotection and Amelioration of Tau Aggregates in Alzheimer's Disease.
Alzheimer's disease (AD) is one of the major age related neurodegenerative diseases whose pathology arises due to the presence of two distinct protein aggregates, viz., amyloid-β plaques in extracellular matrix and tau neurofibrillary tangles in neurons. Multiple factors play a role in AD pathology, which includes familial mutations, oxidative stress, and post-translational modifications. Melatonin is an endocrine hormone, secreted during darkness, derived from tryptophan, and produced mainly by the pineal gland. It is an amphipathic molecule, which makes it suitable to cross not only blood-brain barrier, but also to enter several other subcellular compartments like mitochondria and endoplasmic reticulum. In this context, the neuroprotective effect of melatonin may be attributed to its role as an antioxidant. Melatonin's pleiotropic function as an antioxidant and neuroprotective agent has been widely studied. However, its direct effect on the aggregation of tau and amyloid-β needs to be explored. Furthermore, an important aspect of its function is its ability to regulate the process of phosphorylation of tau by affecting the function of kinases and phosphatases. In this review, we are focusing on the pleiotropic function of melatonin on the aspect of its neuroprotective function in tau pathology, which includes antioxidant function, regulation of enzymes, including kinases and enzymes involved in free radical scavenging and mitochondrial protection.


Simultaneous, continuous, on-line and real-time spectral analysis of multiple physiologic signals by a personal-computer-based algorithm.
We presented in this communication a computer algorithm that offers the advantage of simultaneous analysis of the power spectrum of multiple physiologic signals, including systemic arterial pressure, single-neuronal and electroencephalographic signals, on a continuous, on-line and real-time basis. It provided sensitive definition, discrimination and quantification (graphic and digital) of the various frequency components in the spectrum. There was also great flexibility in selecting the physiologic signal(s) to be analyzed, the choice of results of analysis to be displayed for each physiologic parameter and the alteration of sensitivity and baseline of each event channel. Furthermore, it included window options to improve the frequency or temporal resolution and discrimination of the spectral changes. Most importantly, all these desirable features can be accomplished economically with a general purpose personal computer.


Hemodynamic effects of different modes of mechanical ventilation in acute cardiac and pulmonary failure: an experimental study.
To determine the hemodynamic effects of four different modes of mechanical ventilation in an animal model of acute cardiac and pulmonary failure. Prospective, randomized, crossover design. University research laboratory. Twelve piglets weighing 10 to 16 kg. The experimental protocol consisted of three stable 30-min periods: when ventricular and pulmonary functions were normal (control), after the induction of acute cardiac failure by the administration of a beta-adrenergic receptor blocker, and after pulmonary failure induced by repeated lung lavage. Modes of mechanical ventilation included controlled mechanical ventilation, high-frequency oscillation, synchronized high-frequency jet ventilation, and external negative pressure oscillation combined with pressure support ventilation. Each mode of respiratory support was randomly and sequentially applied to each animal with the assessment of cardiopulmonary function at the end of each period. Continuous monitoring included electrocardiogram, right atrial, left ventricular end-diastolic, pulmonary arterial, intrathoracic aortic, arterial, esophageal, and transpulmonary pressures and arterial and mixed venous oxygen saturation measurements. In addition, cardiac output using the thermodilution technique was measured intermittently. Whereas in the control period cardiac index was significantly (p < .05) higher during synchronized high-frequency jet ventilation (193 +/- 19.3 mL/kg/min) than during controlled mechanical ventilation (151 +/- 12.1 mL/kg/min) and high-frequency oscillation (151 +/- 18.1 mL/kg/min), there was no significant hemodynamic difference between the four modes of mechanical ventilation in the cardiac and pulmonary failure periods. In the pulmonary failure period, transpulmonary pressure was significantly higher during high-frequency oscillation (7.1 +/- 1.6 mm Hg) than during controlled mechanical ventilation (5.6 +/- 0.6 mm Hg), high-frequency ventilation (4.1 +/- 0.4 mm Hg), and external negative pressure oscillation combined with pressure support ventilation (5.3 +/- 0.5 mm Hg). Synchronized high-frequency ventilation improves cardiac performance in control conditions. No hemodynamic difference is present between the four modes of mechanical ventilation in the cardiac and pulmonary failure periods. External negative pressure oscillation combined with pressure support ventilation has moderate hemodynamic advantages over controlled mechanical ventilation and high-frequency oscillation in different clinical settings, but it also results in a deterioration of pulmonary gas exchange during the pulmonary failure period.


Regulated expression of a complete human beta-globin gene encoded by a transmissible retrovirus vector.
We introduced a human beta-globin gene into murine erythroleukemia (MEL) cells by infection with recombinant retroviruses containing the complete genomic globin sequence. The beta-globin gene was correctly regulated during differentiation, steady-state mRNA levels being induced 5- to 30-fold after treatment of the cells with the chemical inducer dimethyl sulfoxide. Studies using vectors which yield integrated proviruses lacking transcriptional enhancer sequences indicated that neither retroviral transcription nor the retroviral enhancer sequences themselves had any obvious effect on expression of the globin gene. Viral RNA expression also appeared inducible, being considerably depressed in uninduced MEL cells but approaching normal wild-type levels after dimethyl sulfoxide treatment. We provide data which suggest that the control point for both repression and subsequent activation of virus expression in MEL cells lies in the viral enhancer element.


Archaeal Lsm rings as stable self-assembling tectons for protein nanofabrication.
We have exploited the self-assembling properties of archaeal-derived protein Lsmα to generate new supramolecular forms based on its stable ring-shaped heptamer. We show that engineered ring tectons incorporating cysteine sidechains on obverse faces of the Lsmα7 toroid are capable of forming paired and stacked formations. A Cys-modified construct, N10C/E61C-Lsmα, appears to organize into disulfide-mediated tube formations up to 45 nm in length. We additionally report fabrication of cage-like protein clusters through conjugation of Cu2+ to His-tagged variants of the Lsmα7 tecton. These 400 kDa protein capsules are seen as cube particles with visible pores, and are reversibly dissembled into their component ring tectons by EDTA. The β-rich Lsmα supramolecular assemblies described are amenable to further fusion modifications, or for surface attachment, so providing potential for future applications that exploit the RNA-binding capacity of Lsm proteins, such as sensing applications.


The coordination chemistry of the hydrotris(3-diphenylmethylpyrazol-1-yl)borate (Tp(CHPh2)) ligand.
The new ligand, hydrotris[3-(diphenylmethyl)pyrazol-1-yl]borate, Tp(CHPh2), has been synthesized and its coordination chemistry was compared with that of the analogous Tp(iPr). The new ligand was converted to a variety of complexes, such as M[Tp(CHPh2)]X (M = Co, Ni, Zn; X = Cl, NCO, NCS), Pd[Tp(CHPh2)][eta3-methallyl], Co[Tp(CHPh2)](acac), and Co[Tp(CHPh2)](scorpionate ligand). Compounds Tl[Tp(CHPh2)], 1, Co[Tp(CHPh2)]Cl, 2, Co[Tp(CHPh2)](NCS)(DMF), 3, Ni[Tp(CHPh2)](NCS)(DMF)2, 4, Co[Tp(CHPh2)](acac), 5, Co[Tp(CHPh2)][Ph2Bp], 6, Co[Tp(CHPh2)][Bp(Ph)], 7, Co[Tp(CHPh2)][Tp], 8, and (Ni[Tp(CHPh2)])2[C2O4](H2O)2, 9, were structurally characterized.


Role of astakine1 in regulating transglutaminase activity.
Transglutaminase (TGase) has been implicated in maintaining the undifferentiated stage of hematopoietic stem cells (HSC) in the crayfish Pacifastacus leniusculus. TGase activity has been reported to be regulated by astakine1, an essential crayfish cytokine for inducing new hemocyte synthesis in hematopoietic tissue (HPT). Here, the role of astakine1 in TGase activity regulation and clotting protein (CP) cross-linking was characterized. A reduction in TGase activity was observed by the addition of purified astakine1 in vitro for both endogenous crayfish TGase and a commercial purified guinea pig liver TGase. As a result, we observed that astakine1 inhibits TGase enzyme activity and acts as a non-competitive inhibitor for the TGase enzyme. Additionally, the clotting reaction was impaired in the presence of astakine1. A decrease in TGase-mediated crosslinking of ε(γ-glutamyl)-lysine bonds was also observed in the presence of astakine1. In conclusion, this study shows that astakine1 acts as an inhibitor of TGase activity and that it also affects CP cross-linking during crayfish hematopoiesis.


[Experimental evaluation of therapeutic-prophylactic nutrition in exposure to acrylonitrile].
The purpose of the work was to study the prophylactic effect of a synthetic complete ration with an addition of L-cysteine in doses of 300 and 150 mg/kg and also investigation of the protective action exerted by 3 rations with varying content of protein (10, 18 and 30 per cent) and calorific value with a repeated and chronic inhalation of AAN in concentrations of 20 +/- 5 and 9 +/- 2.8 mg/m3. The effectiveness of the food rations under study was evaluated basically according to metabolic criteria. The metabolic indices were found to be the most sensitive ones and changing early following the effect of AAN. For this reason they may serve as criteria for not only assessing the noxious action of the poison, but also in devising the type of the medico-prophylactic dietary.


Posterior optic buttonholing of intraocular lens implantation through posterior capsulorrhexis margin: A technique of intraocular lens implantation in cases of anterior capsulorrhexis extension in pediatric cataract surgery.
This study aimed to evaluate the intra- and postoperative complications of intraocular lens (IOL) implantation with posterior optic buttonholing (POBH) in children that had undergone phacoemulsification irrigation/aspiration for congenital/developmental cataract and experienced complication of anterior capsulorrhexis extension (ACE). A total of 25 eyes of 21 patients were included in the study. A foldable three-piece IOL was implanted into the bag/ciliary sulcus with primary posterior capsulorrhexis and POBH. The visual acuity improved from 2.12 ± 0.69 log MAR to 1.38 ± 0.49 log MAR at 6 months follow-up. Postoperative complications included heightened postoperative inflammation in three patients and temporary corneal edema in two patients. Only one patient had developed posterior capsular opacification (PCO) at 6 months follow-up with mild tilt, while the rest 24 eyes had no PCO formation and adequate IOL centration. The results of this study indicate that a three-piece foldable IOL implantation with POBH is a feasible option for children who experienced ACE during pediatric cataract surgery, as it results in satisfactory surgical outcomes and very few ocular complications.


Division and motility of mitochondria in sea urchin embryogenesis.
The influence of actin and tubulin cytoskeletons on the shape, division and on intracellular motility of mitochondria was studied in eggs and embryos of the sea urchin Paracentrotus lividus. Depolymerization of actin filaments and microtubules was induced by specific inhibitors as cytochalasin D (CytD) and colcemid respectively. The quantitative analysis of the mitochondrial population shows that: 1) the chondriome of an egg consists of numerous (about 15,000) discrete mitochondrial clusters uniformly distributed throughout the cytoplasm, each cluster containing 10 to 20 mitochondria of spherical or rod-like shape; 2) fertilization induces cluster break-down and mitochondrial division within 15 min after insemination; at 100 min after fertilization mitochondria become evenly distributed throughout the cytoplasm and the population of mitochondria doubles; 3) in embryos obtained from eggs inseminated after treatment with CytD clusters break-down and mitochondriokinesis are blocked; 4) when added 15 min after insemination, CytD uncouples coordinated invagination of outer and inner membranes in dividing mitochondria thus bringing about abnormal mitochondriokinesis; 5) the treatment of the eggs with colcemid does not affect the normal embryonic mitochondriokinesis.


A structural and functional analysis of opal stop codon translational readthrough during Chikungunya virus replication.
Chikungunya virus (CHIKV) is an alphavirus, transmitted by Aedes species mosquitoes. The CHIKV single-stranded positive-sense RNA genome contains two open reading frames, coding for the non-structural (nsP) and structural proteins of the virus. The non-structural polyprotein precursor is proteolytically cleaved to generate nsP1-4. Intriguingly, most isolates of CHIKV (and other alphaviruses) possess an opal stop codon close to the 3' end of the nsP3 coding sequence and translational readthrough is necessary to produce full-length nsP3 and the nsP4 RNA polymerase. Here we investigate the role of this stop codon by replacing the arginine codon with each of the three stop codons in the context of both a subgenomic replicon and infectious CHIKV. Both opal and amber stop codons were tolerated in mammalian cells, but the ochre was not. In mosquito cells all three stop codons were tolerated. Using SHAPE analysis we interrogated the structure of a putative stem loop 3' of the stop codon and used mutagenesis to probe the importance of a short base-paired region at the base of this structure. Our data reveal that this stem is not required for stop codon translational readthrough, and we conclude that other factors must facilitate this process to permit productive CHIKV replication.


H7N9 Influenza Virus Is More Virulent in Ferrets than 2009 Pandemic H1N1 Influenza Virus.
The novel H7N9 influenza virus has been infecting humans in China since February 2013 and with a mortality rate of about 40%. This study compared the pathogenicity of the H7N9 and 2009 pandemic H1N1 influenza viruses in a ferret model, which shows similar symptoms to those of humans infected with influenza viruses. The H7N9 influenza virus caused a more severe disease than did the 2009 pandemic H1N1 influenza virus. All of the ferrets infected with the H7N9 influenza virus had died by 6 days after infection, while none of those infected with the 2009 pandemic H1N1 influenza virus died. Ferrets infected with the H7N9 influenza virus had higher viral titers in their lungs than did those infected with the 2009 pandemic H1N1 influenza virus. Histological findings indicated that hemorrhagic pneumonia was caused by infection with the H7N9 influenza virus, but not with the 2009 pandemic H1N1 influenza virus. In addition, the lung tissues of ferrets infected with the H7N9 influenza virus contained higher levels of chemokines than did those of ferrets infected with the 2009 pandemic H1N1 influenza virus. This study suggests that close monitoring is needed to prevent human infection by the lethal H7N9 influenza virus.


[Investigation of core Y-haplogroups frequency occuring in Moscow and Saint-Petersburg citizens].
A DNA collection of 239 Moscow and 62 SPB citizens has been investigated by means of a biochip for genotyping of Y-chromosome haplogroup markers: M130 (C), M145 (DE), P257 (G), M69 (H), U179 (I), M304 (J), M185 (L), M231 (N), M175 (0), P224 (R), L146 (R1a) and M343 (R1b). Haplogroup frequency distribution in populations native to Moscow and Saint-Petersburg has been obtained. Three subsamples varying in duration of residence (one, two or three generations) were compared. Increasing of J, G, R1b frequencies may be related to immigration from Caucasia and other regions.


Hydrogen storage in clathrate hydrates.
Structure, stability, and reactivity of clathrate hydrates with or without hydrogen encapsulation are studied using standard density functional calculations. Conceptual density functional theory based reactivity descriptors and the associated electronic structure principles are used to explain the hydrogen storage properties of clathrate hydrates. Different thermodynamic quantities associated with H(2)-trapping are also computed. The stability of the H(2)-clathrate hydrate complexes increases upon the subsequent addition of hydrogen molecules to the clathrate hydrates. The efficacy of trapping hydrogen molecules inside the cages of clathrate hydrates in an endohedral fashion depends upon the cavity sizes and shapes of the clathrate hydrates. Computational studies reveal that 5(12) and 5(12)6(2) structures are able to accommodate up to two H(2) molecules whereas 5(12)6(8) can accommodate up to six hydrogen molecules. Adsorption and desorption rates conform to that of a good hydrogen storage material.


Multipolar Field Shaping in a Suprachoroidal Visual Prosthesis.
Visual prostheses are now an available mobility aid for patients blinded by degenerative retinal diseases. However, the spatial resolution of existing devices is still insufficient to deliver normal levels of mobility vision without stimulation strategies, which enable existing devices to deliver several different percepts per stimulation site. A stimulation strategy, in which field shaping is achieved by incorporating multipolar (bipolar and tripolar) stimulation could convey additional information to a user of a visual prosthesis, as compared with monopolar stimulation, is investigated. Electrical stimulus response thresholds were simulated using morphologically and physiologically accurate cable models of human retinal ganglion cell (RGC) axons. From the population response patterns which could be evoked in simulation, multipolar field-shaping stimulation from one location could convey as much information as monopolar array stimulation. This result is confirmed in vitro by applying a Bayesian classification analysis to multielectrode array recordings of RGC population responses to extracellular stimulation. In vitro recorded population responses to individual stimuli in vitro could be used to train a Baysian classifier, which could correctly identify individual stimuli as predicted by the simulated population responses. In both simulation and in vitro experiments, monopolar thresholds were not significantly different to multipolar thresholds.


Detection of drug bioactivation in vivo: mechanism of nevirapine-albumin conjugate formation in patients.
The non-nucleoside reverse transcriptase inhibitor nevirapine (NVP) is widely used for the treatment of human immunodeficiency virus type 1 (HIV-1), particularly in developing countries. Despite its therapeutic benefits, NVP has been associated with skin and liver injury in exposed patients. Although the mechanism of the tissue injury is not yet clear, it has been suggested that reactive metabolites of NVP may be involved. The detection of NVP mercapturate in the urine of patients undergoing standard antiretroviral chemotherapy indicates that NVP undergoes bioactivation in vivo. However, covalent binding of drug to protein in patients remains to be determined. In this study, we investigate the chemical basis of NVP protein adduct formation by using human serum albumin (HSA) and glutathione S-transferase pi (GSTP) as model proteins in vitro. In addition, HSA was isolated from serum samples of HIV-1 patients undergoing NVP therapy to measure NVP haptenation. Mass spectrometric analysis of 12-sulfoxyl-NVP-treated HSA revealed that the drug bound selectively to histidine (His146, His242, and His338) and a cysteine residue (Cys34). The reaction proceeds most likely by a concerted elimination-addition mechanism. This pathway was further confirmed by the observation of NVP-modified Cys47 in GSTP. Importantly, the same adduct (His146) was detected in HSA isolated from the blood of patients receiving NVP, providing direct evidence that NVP modifies protein in vivo, via the formation of a reactive metabolite.


Pristimantis in the Eastern Brazilian Amazon: DNA barcoding reveals underestimated diversity in a megadiverse genus.
The genus Pristimantis has the highest species diversity among all terrestrial vertebrates, with most species observed in the Andean region and the Guiana Shield. Even with the recent description of a new species, only P. latro, P. dundeei and P. zimmermanae occur in the south of the Amazon River. The lack of taxonomists specialized in the field leads to the propagation of dubious terminologies (e.g. Pristimantis sp1, Pristimantis sp2, P. aff. Fenestratus and P. gr. conspicillatus) or even misidentification of species, resulting in erroneous species distributions. In this study, we applied the Automatic Barcode Gap Discovery (ABGD) algorithm for the delimitation of candidate species and values of genetic distances using the mitochondrial marker Cytochrome Oxidase Subunit I (COI), proposed in the barcode methodology, where values greater than 10% are considered as indicative of different species. We found large genetic distances between P. latro and Pristimantis sp1 Unconfirmed Candidate Species - UCS1 (21%), and between P. altamazonicus and Pristimantis sp2 UCS2 (14%). The ABGD method recognized UCS1 and UCS2 as distinct species. Pristimantis sp. UCS1 and UCS2 in the east of the Brazilian Amazon are indicated as candidate species. We suggest greater sampling of Pristimantis sp. UCS1 and UCS2, integrating morphology and bioacoustics to solve the taxonomic status in the east of the Brazilian Amazon.


Conditional impairment of cell division and altered lethality in hipA mutants of Escherichia coli K-12.
Mutations in hipA, a gene of Escherichia coli K-12, greatly reduce the lethality of selective inhibition of peptidoglycan synthesis. These mutations have also been found to reduce the lethality that accompanies either selective inhibition of DNA synthesis or heat shock of strains defective in htpR. In addition, the mutant alleles of hipA are responsible for a reversible cold-sensitive block in cell division and synthesis of macromolecules, particularly peptidoglycan. Recombination between the chromosome of hipA mutants and plasmids containing noncomplementing fragments of hipA+ revealed that the mutations responsible for both cold sensitivity and reduced lethality were probably identical and, in any case, lay within the first 360 base pairs of the coding region of hipA, probably within the first 50 base pairs. We suggest that the pleiotropic effects of mutations in hipA reflect the involvement of this gene in cell division.


Extensive halogen-mediated ozone destruction over the tropical Atlantic Ocean.
Increasing tropospheric ozone levels over the past 150 years have led to a significant climate perturbation; the prediction of future trends in tropospheric ozone will require a full understanding of both its precursor emissions and its destruction processes. A large proportion of tropospheric ozone loss occurs in the tropical marine boundary layer and is thought to be driven primarily by high ozone photolysis rates in the presence of high concentrations of water vapour. A further reduction in the tropospheric ozone burden through bromine and iodine emitted from open-ocean marine sources has been postulated by numerical models, but thus far has not been verified by observations. Here we report eight months of spectroscopic measurements at the Cape Verde Observatory indicative of the ubiquitous daytime presence of bromine monoxide and iodine monoxide in the tropical marine boundary layer. A year-round data set of co-located in situ surface trace gas measurements made in conjunction with low-level aircraft observations shows that the mean daily observed ozone loss is approximately 50 per cent greater than that simulated by a global chemistry model using a classical photochemistry scheme that excludes halogen chemistry. We perform box model calculations that indicate that the observed halogen concentrations induce the extra ozone loss required for the models to match observations. Our results show that halogen chemistry has a significant and extensive influence on photochemical ozone loss in the tropical Atlantic Ocean boundary layer. The omission of halogen sources and their chemistry in atmospheric models may lead to significant errors in calculations of global ozone budgets, tropospheric oxidizing capacity and methane oxidation rates, both historically and in the future.


Communication between science and management.
Four methods of communication between science and management are conceivable: (1) authoritative science, which provides results without explanation or justification; (2) authoritative management with imposition of a preconceived management decision on science, which destroys independence and credibility of the scientist; (3) usurpation or mutual invasion of both science and management into each other's territory, which is detrimental to the integrity of both; and (4) interaction between scientist and manager, in which the different tasks of both are recognized and respected. For the latter it is important to accept that the commitment of the scientist is to science only and that managers are committed to other considerations besides science. The role of the scientist is easier because of their commitment, and the results of their work are less likely to be questioned, when they succeed in communicating their working methods, treatment of (missing) data, deductions, and results in a comprehensible and logical form. The manager, however, will be in a difficult position, if these results take the form of advice which, for whatever reasons, they cannot follow. Managers may be tempted to avoid advice or, if unavoidable, to doubt its correctness or to modify its meaning, instead of justifying their decision. The major problem in communication between science and management is probably in semantics: the wording of the task of the scientist and of the scientific result in unambiguous language which is understood by the assessor and the manager, respectively.


Presence and possible function of root effect hemoglobins in fishes lacking functional swim bladders.
The adult hemoglobins of 15 species of teleost and the midgestation fetal hemoglobin of the seaperch Embiotoca lateralis show a pronounced decrease in oxygen-carrying capacity at low pH, a Root effect. All of these fishes lack a functional swim bladder, which is generally thought to be the likely site of Root effect hemoglobin function. All of the teleosts examined, including the fetal sea perch, however, have a choroid rete, a structure that is proposed to be involved in oxygen secretion to the eye. The data are inconsistent with the generalization that only fishes with swim bladders possess Root effect hemoglobins, and that the only function of Root effect hemoglobins is in the secretion of oxygen to a swim bladder. The data for the fishes examined in this study suggests that a better correlation may exist between Root effect hemoglobins and the presence of a choroid rete. This is consistent with the hypothesis that Root effect hemoglobins may be involved in the physiology of the eye in many fishes.


The promise and challenges of blood spot methylomics.
Epigenome-wide association studies (EWAS) are being extensively performed to identify epigenetic variants associated to complex diseases. However, EWAS may identify variants that are disease-induced rather than disease-causal. Recent studies have highlighted the use of Guthrie cards to profile the methylome at birth, permitting researchers to find epigenetic variants present in patients before they are diagnosed with clinical disease, with the implicit suggestion that these variants are more likely to be disease causal. The use of Guthrie cards for research purposes throws up a number of ethical issues. We review here the promises and pitfalls of Guthrie cards for disease research.


Short-Term Outcome of Discharged Low-Risk Chest Pain without Provoke Ischemia Study.
Chest pain is a common problem in patients referring to emergency units. The present study was undertaken to evaluate the short-term outcome of patients presenting with a low risk chest pain and discharging without provoke ischemia study during emergency department admission. In the present prospective cohort study, patients with low-risk chest pain, referring to the emergency department of Imam Hossein Hospital, Tehran, during the first half of 2012, were evaluated. All the patients underwent electrocardiogram (ECG) and cardiac enzyme tests, including cardiac isoenzymes creatine kinase MB and troponin I. One week after referring to the emergency department, the patients underwent an exercise test and were followed for a month. Data were analyzed with chi-squared test at a significant level of P<0.05. A total of 252 patients were included. The mean and standard deviation of patient ages was 56±7.7 years (47.5% male). The results of exercise tests for 47 (26.3%) subjects were positive [32 (28.8%) patients in the 41-60 year age group and 15 (22.7%) over 60 years of age].The angiography examination results of 5 patients (2.8%) were abnormal. There were no significant relationships between the age and gender and the results of exercise test and angiography (P>0.05). During the one-month follow-up no cases of mortality, cardiac problems, or referring again to the hospital were recorded. Based on the results of the present study, prevalence of cardiac etiology in patients with low risk chest pain was 2.8% and one-month follow-up did not reveal any complications or serious problems in such cases.


Study on Rheological Behavior and Surface Properties of Epoxy Resin Chemical Grouting Material Considering Time Variation.
Epoxy resins are widely used for repairing cracks in stone, mortar and masonry. A main factor that influences the grouting quality is the permeability of grout. However, the permeability will deteriorate over time because of the reaction of chemical grouting materials, which will greatly affect the results of grouting. To the best of our knowledge, there are few reports that focus on the time-varying properties of viscosity and affinity of epoxy resins grouting material. In this paper, we investigate the changing rules of viscosity and affinity with time by studying the viscosity, surface tension and contact angle of the epoxy grouting material. We establish the mathematical model for the time-dependent properties of CW epoxy resin on viscosity and affinity with experimental verification. Moreover, we make a detailed discussion on the modeling of viscosity variation considering both time and temperature. The results show important guiding significance and application value for judging the grout irrigability in the construction process.


Sequential combination of systemic high-dose ara-C and asparaginase for the treatment of central nervous system leukemia and lymphoma.
Eight patients with overt central nervous system (CNS) leukemia and lymphoma were treated with sequential administration of systemic high-dose cytosine arabinoside (HiDAC) and asparaginase (ASP) with no direct CNS therapy. Complete clearing of the cerebrospinal fluid (CSF) was achieved in six (86%) of seven patients with meningeal disease, generally after the first course of therapy. Two patients presented with evidence of extensive intracerebral disease; both responded with a greater than 50% regression of the tumor infiltrates. Concomitant extraneurologic localizations responded equally well to HiDAC/ASP: responses were seen in four of five patients, including complete remission in three of four patients who presented with marrow involvement. Toxicity was generally moderate and limited to myelosuppression (eight of eight patients), tolerable nausea and vomiting (eight of eight patients), mild hepatotoxicity (two of eight patients), and oral mucositis (one of eight patients). These results indicate that HiDAC/ASP is a tolerable and highly effective treatment modality for CNS leukemia and lymphoma and suggest its potential role for sanctuary chemoprophylaxis.


Syphilis: Re-emergence of an old foe.
Syphilis is caused by infection with Treponema pallidum subsp. pallidum, a not-yet-cultivable spiral-shaped bacterium that is usually transmitted by sexual contact with an infected partner or by an infected pregnant woman to her fetus. There is no vaccine to prevent syphilis. Diagnosis and treatment of infected individuals and their contacts is key to syphilis control programs that also include sex education and promotion of condom use to prevent infection. Untreated syphilis can progress through four stages: primary (chancre, regional lymphadenopathy), secondary (disseminated skin eruptions, generalized lymphadenopathy), latent (decreased re-occurrence of secondary stage manifestations, absence of symptoms), and tertiary (gummas, cardiovascular syphilis and late neurological symptoms). The primary and secondary stages are the most infectious. WHO estimates that each year 11 million new cases of syphilis occur globally among adults aged 15-49 years. Syphilis has re-emerged in several regions including North America, Western Europe, China and Australia. Host-associated factors that drive the re-emergence and spread of syphilis include high-risk sexual activity, migration and travel, and economic and social changes that limit access to health care. Early, uncomplicated syphilis is curable with a single intramuscular injection of benzathine penicillin G (BPG), the first line drug for all stages of syphilis. Emergence of macrolide-resistant T. pallidum has essentially precluded the empirical use of azithromycin as a second-line drug for treatment of syphilis. Virulence attributes of T. pallidum are poorly understood. Genomic and proteomic studies have provided some new information concerning how this spirochete may evade host defense mechanisms to persist for long periods in the host.


Mental retardation and learning disabilities: conceptual and applied issues.
The relationship between mental retardation and learning disabilities is clouded by conceptual issues and current practices in applied (i.e., educational and noneducational) settings. In this article, we initially discuss whether mental retardation can be considered a concomitant disability associated with learning disabilities or whether these two disabilities are mutually exclusive categories. Conceptual issues related to this question are then reviewed to provide a perspective for viewing these two traditional areas of exceptionality. Emerging areas of concern in term of definition, classification, etiology, and lifelong issues are addressed. Attention is then given to applied issues that have a direct effect on the lives of individuals with disabilities. Specific topics include educational curricula, instruction, inclusion, and adult services and supports.


Long-stay forensic psychiatric inpatients in the Republic of Ireland: aggregated needs assessment.
To profile the current cohort of forensic psychiatric inpatients in the Republic of Ireland, comparing psychiatric healthcare and placement needs of long-stay patients with those more recently admitted. All forensic psychiatric inpatients in the Central Mental Hospital, Dundrum on a census date were included in the study. Patients and key worker were interviewed using a standardised schedule and validated research instruments. Static and dynamic risk factors for violence including demographic, diagnostic and legal characteristics were supplemented by detailed chart review. Standardised anonymised case vignettes were presented to panels of forensic and community psychiatric multidisciplinary teams who assessed current and future treatment and placement requirements for the cohort. There were 88 forensic psychiatric inpatients on the census date. Forty-three had lengths of stay over two years (17 over 20 years). Both patient groups were predominantly males with severe mental illness and histories of violent offending. The majority of the long-stay group were receiving regular parole and this group had lower levels of positive symptoms and comorbid substance misuse disorders. Significant gaps in existing rehabilitation inputs were identified. Almost half the long-stay patients were inappropriately placed. Thirty per cent of long-stay patients could be safely transferred to lower levels of security within six months and 63% within three years. Holding patients in conditions of excessive security impedes rehabilitation and has considerable human rights implications. Almost half of long-stay forensic psychiatric patients in Ireland are inappropriately placed. Barriers to discharge include legislative inadequacies, lack of local low-secure facilities and under-resourcing of community psychiatric services. Such barriers lead to inappropriate utilisation of limited resources and limit access to secure facilities for higher-risk mentally disordered offenders. These findings are of particular relevance in the context of proposed new insanity legislation.


Associations between fatigue and medication use in chronic rhinosinusitis.
We conducted a prospective study of 586 adults to determine if associations exist between fatigue symptom scores and three classes of medications prescribed for the treatment of chronic rhinosinusitis (CRS): prescription nonsedating antihistamines, topical nasal steroids, and antibiotics. Patients were assessed with the assistance of the Rhinosinusitis Symptom Inventory and Likert-scale fatigue symptom scores. On multivariate analysis and correcting or disease severity, we found that significantly higher fatigue symptom scores were associated with the use of nonsedating antihistamines (mean Likert score: 2.75 vs. 2.27 for patients not taking a nonsedating antihistamine; p = 0.029). Higher fatigue scores were also associated with a greater number of antibiotic courses and more total weeks of antibiotic use (p < 0.001 in both cases). No association was seen between fatigue scores and the use of topical nasal steroids (mean Likert score: 2.65 vs. 2.24; p = 0.658). We recommend that long-term use of a nonsedating antihistamine be scrutinized in CRS patients who report symptoms of fatigue.


Successful catheter ablation of hemodynamically unstable monomorphic ventricular tachycardia in a patient with hypertrophic cardiomyopathy and apical aneurysm.
Patients with hypertrophic cardiomyopathy (HCM) and left ventricular (LV) apical aneurysm represent a previously under-recognized but important subgroup within this heterogeneous disease spectrum. Apical aneurysms and the contiguous areas of myocardial fibrosis have been associated with monomorphic ventricular tachycardia (VT) and increased risk for adverse clinical events including sudden cardiac death, prioritizing the application of primary prevention implantable defibrillators. However, VT may be repetitive, thereby raising considerations for additional treatment strategies such as radiofrequency ablation. In this report, we describe such a patient with HCM and apical aneurysm in whom the mapping and ablation procedure was effective in identifying and abolishing the VT focus.


Lower urinary tract dysfunction in pelvic gynecologic cancer: the role of urodynamics.
The exact incidence of lower urinary tract dysfunction is not known and its pathogenesis is not completely understood. Advances in urodynamic assessment and widespread availability of a standardized technique have facilitated its exploration prior to and subsequent to the surgical management of patients with gynecologic pelvic cancer. We performed a PubMed and Medline literature search using the following keywords: bladder dysfunction, urinary dysfunction, and urodynamics and all these terms in combination with radical hysterectomy in order to analyze the role of urodynamics in patients with pelvic gynecologic cancer in the preoperative as well as in the early and late postoperative settings.


Chloro boron subphthalocyanine and its derivatives: dyes, pigments or somewhere in between?
Nine derivatives of chloro boron subphthalocyanine (Cl-BsubPc, 1) have been synthesized and characterized. Seven dimers of Cl-BsubPc have been synthesized by reaction with biphenol (2a), bisphenol A (2b), bisphenol F (2c), bisphenol O (2d), bisphenol P (2e), bisphenol S (2f) and bisphenol Z (2g). For comparison two monomeric phenoxy- (3a) and 4-methylphenoxy (3b) BsubPcs have also been synthesized. Crystals were grown for dimer 2c, whereas all attempts to grow crystals of the remaining dimers resulted in the formation of molecular glasses or amorphous precipitates. Analysis on the structure of 2c suggests that the rigidity and aromatic nature of the central bisphenolic directs the crystal packing. The solubility of the BsubPc dimers in a variety of common organic solvents was measured and compared to that of Cl-BsubPc (2) and monomers 3a and 3b. We have defined ranges for classifying BsubPc derivatives based on their solubility in these solvents: pigment < or = 1 x 10(-8) M, 1 x 10(-3) M < or = pigment-like > 1 x 10(-8) M, 1 x 10(-2) M < or = dye-like > 1 x 10(-3) M, and dye > 1 x 10(-2) M. From this Cl-BsubPc (1) and compounds 2a, 2b, 2c, 2e and 2g are pigment-like while compounds 2d, 2f, 3a and 3b are dye-like. None are exclusively pigments or dyes. In this first approximation of this dye versus pigment classification we have not considered other processes besides solvation which could be undesirable such as polymorphic changes or Ostwald ripening. We have concluded that derivatization of Cl-BsubPc (1) with bisphenols and phenols can be used to control the solubility of BsubPc derivatives. We have also concluded that Cl-BsubPc (1) should not be considered a dye rather is pigment-like in its solubility.


Cell survival signalling through PPARδ and arachidonic acid metabolites in neuroblastoma.
Retinoic acid (RA) has paradoxical effects on cancer cells: promoting cell death, differentiation and cell cycle arrest, or cell survival and proliferation. Arachidonic acid (AA) release occurs in response to RA treatment and, therefore, AA and its downstream metabolites may be involved in cell survival signalling. To test this, we inhibited phospholipase A2-mediated AA release, cyclooxygenases and lipoxygenases with small-molecule inhibitors to determine if this would sensitise cells to cell death after RA treatment. The data suggest that, in response to RA, phospholipase A2-mediated release of AA and subsequent metabolism by lipoxygenases is important for cell survival. Evidence from gene expression reporter assays and PPARδ knockdown suggests that lipoxygenase metabolites activate PPARδ. The involvement of PPARδ in cell survival is supported by results of experiments with the PPARδ inhibitor GSK0660 and siRNA-mediated knockdown. Quantitative reverse transcriptase PCR studies demonstrated that inhibition of 5-lipoxygenase after RA treatment resulted in a strong up-regulation of mRNA for PPARδ2, a putative inhibitory PPARδ isoform. Over-expression of PPARδ2 using a tetracycline-inducible system in neuroblastoma cells reduced proliferation and induced cell death. These data provide evidence linking lipoxygenases and PPARδ in a cell survival-signalling mechanism and suggest new drug-development targets for malignant and hyper-proliferative diseases.


Assessing the effect of the VHA PCMH model on utilization patterns among veterans with PTSD.
The Veterans Health Administration (VHA) implemented a patient-centered medical home (PCMH)-based Patient Aligned Care Teams (PACT) model in 2010. We examined its effects on the utilization of health services among US veterans with posttraumatic stress disorder (PTSD). We analyzed VHA clinical and administrative data to conduct an interrupted time series study. Encounter-level data were obtained for the period of April 1, 2005, through March 31, 2014. We identified 642,660 veterans with PTSD who were assigned to either a high- or low-PCMH implementation group using a validated VHA PCMH measurement instrument. We measured the effect of high-PCMH implementation on the count of hospitalizations and primary care, specialty care, specialty mental health, emergency department (ED), and urgent care encounters compared with low-PCMH implementation. We fit a multilevel, mixed-effects, negative binomial regression model and estimated average marginal effects and incidence rate ratios. Compared with patients in low-PCMH implementation clinics, patients who received care in high-PCMH implementation clinics experienced a decrease in hospitalizations (incremental effect [IE], -0.036; 95% confidence interval [CI], -0.0371 to -0.0342), a decrease in specialty mental health encounters (IE, -0.009; 95% CI, -0.009 to -0.008), a decrease in urgent care encounters (IE, -0.210; 95% CI, -0.212 to -0.207), and a decrease in ED encounters (IE, -0.056; 95% CI, -0.057 to -0.054). High PCMH implementation positively affected utilization patterns by reducing downstream use of high-cost inpatient and specialty services. Future research should investigate whether a reduction in utilization of health services indeed results in higher levels of virtual and non-face-to-face access, or if the PACT model has reduced necessary access to care.


On-chip torsion balances with femtonewton force resolution at room temperature enabled by carbon nanotube and graphene.
The torsion balance, consisting of a rigid balance beam suspended by a fine thread, is an ancient scientific instrument, yet it is still a very sensitive force sensor to date. As the force sensitivity is proportional to the lengths of the beam and thread, but inversely proportional to the fourth power of the diameter of the thread, nanomaterials should be ideal building blocks for torsion balances. Here, we report a torsional balance array on a chip with the highest sensitivity level enabled by using a carbon nanotube as the thread and a monolayer graphene coated with Al nanofilms as the beam and mirror. It is demonstrated that the femtonewton force exerted by a weak laser can be easily measured. The balances on the chip should serve as an ideal platform for investigating fundamental interactions up to zeptonewton in accuracy in the near future.


Loss of Plastid Developmental Genes Coincides With a Reversion to Monoplastidy in Hornworts.
The first plastid evolved from an endosymbiotic cyanobacterium in the common ancestor of the Archaeplastida. The transformative steps from cyanobacterium to organelle included the transfer of control over developmental processes, a necessity for the host to orchestrate, for example, the fission of the organelle. The plastids of almost all embryophytes divide independently from nuclear division, leading to cells housing multiple plastids. Hornworts, however, are monoplastidic (or near-monoplastidic), and their photosynthetic organelles are a curious exception among embryophytes for reasons such as the occasional presence of pyrenoids. In this study, we screened genomic and transcriptomic data of eleven hornworts for components of plastid developmental pathways. We found intriguing differences among hornworts and specifically highlight that pathway components involved in regulating plastid development and biogenesis were differentially lost in this group of bryophytes. Our results also confirmed that hornworts underwent significant instances of gene loss, underpinning that the gene content of this group is significantly lower than other bryophytes and tracheophytes. In combination with ancestral state reconstruction, our data suggest that hornworts have reverted back to a monoplastidic phenotype due to the combined loss of two plastid division-associated genes, namely, ARC3 and FtsZ2.


The impact of multimorbidity patterns on health-related quality of life in the general population: results of the Belgian Health Interview Survey.
Chronic diseases and multimorbidity are a major cause of disease burden-for patients, caregivers, and society. Little is known however about potential interaction effects between specific disease combinations. Besides an additive effect, the presence of multiple conditions could also act synergistically or antagonistically regarding the impact on patients' health-related quality of life (HRQoL). The aim was to estimate the impact of coexisting chronic diseases on HRQoL of the adult general Belgian population. The Belgian Health Interview Survey 2018 provided data on self-reported chronic conditions and HRQoL (EQ-5D-5L) for a nationally representative sample. Linear mixed models were used to analyze two-way and three-way interactions of disease combinations on HRQoL. Multimorbidity had a prevalence of 46.7% (≥ 2 conditions) and 29.7% (≥ 3 conditions). HRQoL decreased considerably with the presence of multiple chronic diseases. 14 out of 41 dyad combinations and 5 out of 13 triad combinations showed significant interactions, with a dominant presence of negative/synergistic effects. Positive/antagonistic effects were found in more subjective chronic diseases such as depression and chronic fatigue. Conditions appearing the most frequently in significant disease pair interactions were dorsopathies, respiratory diseases, and arthropathies. Diverse multimorbidity patterns, both dyads and triads, were synergistically or antagonistically associated with lower HRQoL. Tackling the burden of multimorbidity is needed, especially because most disease combinations affect each other synergistically, resulting in a greater reduction in HRQoL. Further knowledge about those multimorbidity patterns with a greater impact on HRQoL is needed to better understand disease burden beyond mortality and morbidity data.


Atypical squamous cells as a diagnostic pitfall in pulmonary Wegener's granulomatosis. A case report.
Wegener's granulomatosis (WG) is characterized by systemic, necrotizing, granulomatous inflammation accompanied by vasculitis. It classically involves the triad of the upper respiratory tract, lungs and kidneys. Isolated pulmonary lesions of WG may present in some patients as pulmonary masses, simulating neoplasms. The features of WG can be suggested by cytologic study. Atypical epithelial cells associated with WG have previously been reported as a cause of a false positive diagnosis of bronchoalveolar carcinoma. In this case the cytologic findings included atypical squamous cells in a background of acute, chronic and granulomatous inflammation. In several respiratory specimens the atypical squamous cells were incorrectly interpreted as diagnostic of squamous cell carcinoma. The correct diagnosis of WG was confirmed with open lung biopsy, which demonstrated necrotizing granulomatous inflammation with geographic necrosis and associated vasculitis. Markedly atypical squamous cells mimicking squamous cell carcinoma can be found accompanying the inflammatory process associated with WG and are a possible diagnostic pitfall. The possibility of WG as well as other inflammatory processes should always be considered in the differential diagnosis of squamous cell carcinoma of the lung. This case is the only reported case of WG in which atypical squamous cells were a diagnostic pitfall, initially suggesting a diagnosis of squamous cell carcinoma.


The neuroleptic malignant syndrome: a missed diagnosis?
The neuroleptic malignant syndrome (NMS) is an idiosyncratic reaction to major tranquilizer drugs characterised by hyperpyrexia, extrapyramidal disorders and altered consciousness. First described in 1968 by Delay and Deniker, early case reports suggested a mortality of between 20 and 30%. Though the syndrome is now more widely recognised, the diversity of its clinical features may not always be appreciated and may lead to diagnostic confusion with other, more common, disorders. We report on two severe cases of NMS: in the first the diagnosis was initially thought to be sepsis from a urinary tract infection, and in the second the primary clinical diagnosis was of a mid brain infarction.