Phloretin attenuates LPS-induced acute lung injury in mice via modulation of the NF-κB and MAPK pathways.
Phloretin, which can be isolated from apple trees, has demonstrable anti-inflammatory and anti-oxidant effects in macrophages. We previously reported that phloretin could inhibit the inflammatory response and reduce intercellular adhesion molecule 1 (ICAM-1) expression in interleukin (IL)-1β-activated human lung epithelial cells. In the present study we now evaluate whether phloretin exposure could ameliorate lipopolysaccharide (LPS)-induced acute lung injury in mice. Intra-peritoneal injections of phloretin were administered to mice for 7 consecutive days, prior to the induction of lung injury by intra-tracheal administration of LPS. Our subsequent analyses demonstrated that phloretin could significantly suppress LPS-induced neutrophil infiltration of lung tissue, and reduce the levels of IL-6 and tumor necrosis factor (TNF)-α in serum and bronchoalveolar lavage fluid. We also found that phloretin modulated myeloperoxidase activity and superoxide dismutase activity, with decreased gene expression levels for chemokines, proinflammatory cytokines, and ICAM-1 in inflamed lung tissue. Phloretin also significantly reduced the phosphorylation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK), thus limiting the inflammatory response, while promoting expression of heme oxygenase (HO)-1 and nuclear factor erythroid 2-related factor 2, both of which are cytoprotective. Our findings suggest that, mechanistically, phloretin attenuates the inflammatory and oxidative stress pathways that accompany lung injury in mice via blockade of the NF-κB and MAPK pathways.


[Temporal spatial distribution of benthic meiofauna in four beaches of the northern Havana shore].
The temporal-spatial distribution of benthic meiofauna was evaluated in four beaches at the north coast of Havana, Cuba, from March 2003 to February 2004. We studied two urban beaches (Santa Fe and La Concha) and two tourist beaches (Mar Azul and Canasi). Monthly meiofauna samplings were taken by scuba-diving using with a syringe (inner diameter 2.5 cm), and physico-chemical parameters (grain size, interstitial salinity and water column salinity were recorded with standard equipment). Statistical analysis (MDS and ANOSIM) were performed. Depth and biotope kind were the same in the four beaches. Highest densities were obtained in Santa Fe (7,133.48 ind/10 cm2) while the lowest mean densities were found in Canasí (892.12 ind/10 cm2). We recorded 13 taxa; the dominant organisms in Santa Fe and Mar Azul were free-living marine nematodes. Copepods were the dominant organisms in La Concha and Canasí.


Suicidal behaviour is associated with decreased esterified cholesterol in plasma and membrane fluidity of platelets.
Altered cholesterol levels in body fluids and brain tissues have been shown to be associated with suicidal behaviour, violence and aggression. But the biological underpinnings of this association in the pathophysiology of suicide are not clear. Cholesterol plays a crucial role in maintaining the cellular membrane fluidity and alterations in cellular membrane fluidity may impair serotonergic neurotransmission in the central nervous system. We measured plasma esterified cholesterol and platelet membrane fluidity using fluorescence anisotropy and estimated flow activation energy which is a measure of order of membrane lipid bilayer in patients with recent suicidal attempt and compared with age and gender matched controls. The plasma esterified cholesterol, platelet membrane fluidity and flow activation energy was found to be significantly lower in patients with recent suicidal attempts compared to controls. Altered levels of plasma esterified cholesterol which is in equilibrium with membrane cholesterol might have resulted in decreased membrane fluidity and an increase in the order of membrane lipid bilayer. This might impair the serotonergic neurotransmission, which has been implicated in the pathophysiology of suicide.


Direct demonstration of the endocytic function of caveolae by a cell-free assay.
The endocytic function of caveolae was challenged by taking advantage of a cell-free assay directly measuring the detachment of receptor-containing vesicles from isolated plasma membranes. Plasma membranes from cultured cells surface-labeled with 125I-cholera toxin (segregating in caveolae) were isolated as described previously. Following incubation of these labeled membranes in the presence of nucleotide(s) and cytosol, a significant proportion of the initially membrane-associated radioactivity was released into the incubation medium in sedimentable form (14*10(6 )g). Results of biochemical, morphological, and fractionation analysis of the material containing the released radioactivity directly demonstrated that caveolae are plasma membrane domains involved in an endocytic process and resulting in the formation of caveolae-derived vesicles. In addition, these studies allowed a direct comparison of caveolae- and clathrin-coated pit-mediated endocytosis and reveal that these two processes diverge in terms of kinetics, cytosol and nucleotide requirements as well as in terms of the density and size of the endocytic vesicles formed.


[The theoretical substantiation of myofunctional correction of sagittal occlusion abnormalities and temporomandibular joint dysfunction].
Simulation in 3D-model of skeletal forms of sagittal malocclusion revealed tendency in tonus' modification of muscles of mastication in formation of distal and mesial occlusion. It's shown that distal occlusion is characterized by hypotonic condition of muscles of mastication, except posterior fibers of temporal muscle. Mesial occlusion is characterized by complex combination of muscle tone with prevalence of hypotonic condition of anterior fibers of temporal muscle, superficial portion of masseter muscle and medial pterygoid muscle. We have detected that using of myofunctional devices in treatment of sagittal malocclusion, temporomandibular joint dysfunction promotes of tone increasing of muscles of mastication.


Virus and cytotoxic T lymphocytes: crucial role of viral peptide secondary structure in major histocompatibility complex class I interactions.
Viral antigens are presented to cytotoxic T lymphocytes (CTLs) by H-2-restricted major histocompatibility complex (MHC) glycoproteins. Binding of the endogenously processed viral peptides (epitopes) to their specific MHC molecules is an early intracellular event in the recognition process and is necessary for subsequent killing of virus-infected cells by virus-specific CTLs. It is now well established that interaction between a viral antigenic peptide and MHC is dependent on the primary structure (length and amino acid sequence) of that antigen. Here we show, using the H-2Db-restricted epitope GP277-286 of lymphocytic choriomeningitis virus as a model, that the secondary structure (conformation) of the viral sequence also plays a crucial role in the binding of a viral antigen to MHC glycoprotein and in its subsequent presentation to virus-specific CTLs.


Effects of human rhinovirus on epithelial barrier integrity and function in children with asthma.
Bronchial epithelial tight junctions (TJ) have been extensively assessed in healthy airway epithelium. However, no studies have yet assessed the effect of human rhinovirus (HRV) infection on the expression and resultant barrier function in epithelial tight junctions (TJ) in childhood asthma. To investigate the impact of HRV infection on airway epithelial TJ expression and barrier function in airway epithelial cells (AECs) of children with and without asthma. Furthermore, to test the hypothesis that barrier integrity and function is compromised to a greater extent by HRV in AECs from asthmatic children. Primary AECs were obtained from children with and without asthma, differentiated into air-liquid interface (ALI) cultures and infected with rhinovirus. Expression of claudin-1, occludin and zonula occluden-1 (ZO-1) was assessed via qPCR, immunocytochemistry (ICC), in-cell western (ICW) and confocal microscopy. Barrier function was assessed by transepithelial electrical resistance (TER; RT ) and permeability to fluorescent dextran. Basal TJ gene expression of claudin-1 and occludin was significantly upregulated in asthmatic children compared to non-asthmatics; however, no difference was seen with ZO-1. Interestingly, claudin-1, occludin and ZO-1 protein expression was significantly reduced in AEC of asthmatic children compared to non-asthmatic controls suggesting possible post-transcriptional inherent differences. HRV infection resulted in a transient dissociation of TJ and airway barrier integrity in non-asthmatic children. Although similar dissociation of TJ was observed in asthmatic children, a significant and sustained reduction in TJ expression concurrent with both a significant decrease in TER and an increase in permeability in asthmatic children was observed. This study demonstrates novel intrinsic differences in TJ gene and protein expression between AEC of children with and without asthma. Furthermore, it correlates directly the relationship between HRV infection and the resultant dissociation of epithelial TJ that causes a continued altered barrier function in children with asthma.


Modification of reactive oxygen species scavenging capacity of chloroplasts through plastid transformation.
Reactive oxygen species (ROS), including superoxide anions, hydrogen peroxide and hydroxyl radicals are generated through normal biochemical processes, but their production is increased by abiotic stresses. The prospects for enhancing ROS scavenging, and hence stress tolerance, by direct gene expression in a vulnerable cell compartment, the chloroplast, have been explored in tobacco. Several plastid transformants were generated which contained either a Nicotiana mitochondrial superoxide dismutase (MnSOD) or an Escherichia coli glutathione reductase (gor) gene. MnSOD lines had a three-fold increase in MnSOD activity, but interestingly a five to nine-fold increase in total chloroplast SOD activity. Gor transgenic lines had up to 6 times higher GR activity and up to 8 times total glutathione levels compared to wild type tobacco. Photosynthetic capacity of transplastomic plants, as measured by chlorophyll content and variable fluorescence of PSII was equivalent to non-transformed plants. The response of these transplastomic lines to several applied stresses was examined. In a number of cases improved stress tolerance was observed. Examples include enhanced methyl viologen (Paraquat)-induced oxidative stress tolerance in Mn-superoxidase dismutase over-expressing plants, improved heavy metal tolerance in glutathione reductase expressing lines, and improved tolerance to UV-B radiation in both sets of plants.


Risk-taking behaviours and beliefs about fertility in university students.
To investigate the risk-taking behaviours and beliefs about fertility among university students in Turkey. Young people are usually ignorant about reproductive health and engage in risky practices. A descriptive cross-sectional study. The convenience sample of the study was consisted of 1030 undergraduate students. Data were collected using a self-administered question form, and students' reproductive health and lifestyle behaviours related with infertility, their beliefs about the risk factors and fertility myths were questioned. The mean age of the students was 20.4 (SD = 2) and ranged between the ages of 16-37. Sexual activity rate was higher among men and 47% of men had more than one sexual partner. Condom use rate was low among women. Underweight was more common among women, while overweight was seen more among men. Students mostly did not exercise regularly. Alcohol was not common, and the rates of smoking were 15% and 23% for women and men, respectively. Only 35-50% of students thought that smoking, alcohol, stress, sexually transmitted diseases, infections, pollution, chemicals, radiation and cancer treatment could be risk factors for fertility. Advanced age and obesity were seen as risk factors for women. Of the students, 50-65% believed that having more than one sexual partner, being underweight, high-level exercise, excessive caffeine, chronic disease and medications could not have an effect on fertility. Women were more concerned about being infertile, and half of students believed that infertility is preventable. Turkish university students have insufficient knowledge of reproductive health, and they have false beliefs that might affect their risk perception or views about fertility. Reproductive healthcare services for young adults should be made more widespread and accessible, and nurses, health providers and instructors should be supportive of them in these matters.


[Optimization of benzalkonium chloride concentration in 0.0015% tafluprost ophthalmic solution from the points of ocular surface safety and preservative efficacy].
Optimization of benzalkonium chloride (alkyl dimethylbenzylammonium chloride: BAK) concentration as preservative in 0.0015% tafluprost ophthalmic solution (Tapros 0.0015% ophthalmic solution), an anti-glaucoma medicine, was examined from the points of ocular surface safety and preservative efficacy. BAKC(12), which is dodecyl dimethylbenzylammonium chloride, and BAKmix, which is the mixture of dodecyl, tetradecyl and hexadecyl dimethylbenzylammonium chloride were used in this study. The effects of BAKC(12) concentrations and the BAK types, BAKC(12) and BAKmix, in tafluprost ophthalmic solution on ocular surface safety were evaluated using the in vitro SV 40-immobilized human corneal epithelium cell line (HCE-T). Following treatments of Tafluprost ophthalmic solutions with BAKC(12), its concentration dependency was observed on cell viability of HCE-T. The cell viability of HCE-T after treatment of these solutions with 0.001% to 0.003% BAKC(12) for 5 minutes were the same level as that after treatment of the solution without BAK. Tafluprost ophthalmic solution with 0.01% BAKC(12) was safer for the ocular surface than the same solution with 0.01% BAKmix. Preservatives-effectiveness tests of tafluprost ophthalmic solutions with various concentrations of BAKC(12) were performed according to the Japanese Pharmacopoeia (JP), and solutions with more than 0.0005% BAKC(12) conformed to JP criteria. It was concluded that 0.0005% to 0.003% of BAKC(12) in tafluprost ophthalmic solution was optimal, namely, well-balanced from the points of ocular surface safety and preservative efficacy.


Stable expression and potential use of west nile virus envelope glycoproteins preM/E as antigen in diagnostic tests.
West Nile virus (WNV) envelope glycoproteins preM/E were stably expressed in baby hamster kidney cells and tested as antigen in a fluorescent antibody assay for WNV antibodies. Sera from horses, mice and chicken immunized with an inactivated WNV vaccine and, less consistently, sera from horses acutely infected with WNV, reacted specifically with viral antigens present in preM/E-expressing cells.


[Useability of an image based nagivation system in reconstruction of leg alignment in total knee arthroplasty - results of a propsective study].
Accurate leg alignment is one important factor for long term survival in total knee arthroplasty (TKA). The aim of this study was to determine the accuracy of a CT-based navigation system in restoration of the leg axis. 80 TKA (P.F.C.-Sigma--DePuy) were implanted either using a CT-based navigation-system or the conventional technique. There were no significant differences between the groups according to the preoperative leg deformity. Accuracy of implantation was determined on postoperative long-leg coronal and lateral x-rays. A postoperative leg axis between 3 degrees varus and 3 degrees valgus was obtained in 35/40 patients (88%) in the computer assisted and 28/40 patients (70%) in the conventional operated group. A higher precision in the sagittal plane was seen for the tibial (computer assisted: 3.9 +/- 2.2 vs. conventional TKA 1.3 +/- 5.8) and the femoral component (computer assisted: 3.5 +/- 2.3 vs. conventional TKA 6.9 +/- 3.6). The use of the CT-based VectorVision-System allows a significant improvement in the accuracy of implantation in TKA. The CT-based module has the advantage of a precise preoperative planning and a useful documentation and control tool for each important step. On the other hand there are additional costs and time consuming logistics.


Imaging diagnosis: fibrodysplasia ossificans progressiva in a cat.
A 1-year-old female cat was presented for progressive alopecia, gait abnormalities, and stiffness. Radiography demonstrated multiple calcified lesions within the soft tissues of the cervical and thoracic spine, shoulder, and limbs. Postmortem computed tomography provided more detailed information on the distribution, pattern, and extension of lesions. In addition, computed tomography helped guide sample selection for histopathology. The final diagnosis was fibrodysplasia ossificans progressiva. This is a rare disorder of unknown etiology, characterized by fibrosis and heterotopic bone formation in connective tissues. To the authors' knowledge, this is the first report describing this disease in a European cat.


[Responses of alpine grassland landscape in the source region of Shule River Basin to topographical factors and frozen ground types].
This paper retrieved the fractional vegetation cover of alpine grassland in the source region of the Shule River Basin based on Chinese environmental satellite (HJ-1A/1B) images and field data, and analyzed the response of the vegetation cover to topographic factors and types of frozen ground. The results showed that the vegetation coverage of this region was low with large spatial heterogeneity and high degree of dispersion. The landscape consisted mainly of non-vegetation surface types, eg. ice, snow, the bare rock gravel land and bare land. Slopes and aspects were the main limiting factors of vegetation distribution. The average vegetation coverage decreased with the increase of slope. The average vegetation coverage was the lowest on the sunny slope, and the highest on the shady slope. There were significant differences of vegetation coverage among different types of frozen ground. The distribution of vegetation coverage presented a reversed "U" curve trend by extremely stable permafrost, stable permafrost, sub-stable permafrost, transition permafrost, unstable permafrost and seasonal frost, and the average vegetation coverage was the highest in the sub-stable permafrost.


Temperature and pathogen exposure act independently to drive host phenotypic trajectories.
Natural populations are experiencing an increase in the occurrence of both thermal stress and disease outbreaks. How these two common stressors interact to determine host phenotypic shifts will be important for population persistence, yet a myriad of different traits and pathways are a target of both stressors, making generalizable predictions difficult to obtain. Here, using the host Daphnia magna and its bacterial pathogen Pasteuria ramosa, we tested how temperature and pathogen exposure interact to drive shifts in multivariate host phenotypes. We found that these two stressors acted mostly independently to shape host phenotypic trajectories, with temperature driving a faster pace of life by favouring early development and increased intrinsic population growth rates, while pathogen exposure impacted reproductive potential through reductions in lifetime fecundity. Studies focussed on extreme thermal stress are increasingly showing how pathogen exposure can severely hamper the thermal tolerance of a host. However, our results suggest that under milder thermal stress, and in terms of life-history traits, increases in temperature might not exacerbate the impact of pathogen exposure on host performance, and vice versa.


Fusobacterium is associated with colorectal adenomas.
The human gut microbiota is increasingly recognized as a player in colorectal cancer (CRC). While particular imbalances in the gut microbiota have been linked to colorectal adenomas and cancer, no specific bacterium has been identified as a risk factor. Recent studies have reported a high abundance of Fusobacterium in CRC subjects compared to normal subjects, but this observation has not been reported for adenomas, CRC precursors. We assessed the abundance of Fusobacterium species in the normal rectal mucosa of subjects with (n = 48) and without adenomas (n = 67). We also confirmed previous reports on Fusobacterium and CRC in 10 CRC tumor tissues and 9 matching normal tissues by pyrosequencing. We extracted DNA from rectal mucosal biopsies and measured bacterial levels by quantitative PCR of the 16S ribosomal RNA gene. Local cytokine gene expression was also determined in mucosal biopsies from adenoma cases and controls by quantitative PCR. The mean log abundance of Fusobacterium or cytokine gene expression between cases and controls was compared by t-test. Logistic regression was used to compare tertiles of Fusobacterium abundance. Adenoma subjects had a significantly higher abundance of Fusobacterium species compared to controls (p = 0.01). Compared to the lowest tertile, subjects with high abundance of Fusobacterium were significantly more likely to have adenomas (OR 3.66, 95% CI 1.37-9.74, p-trend 0.005). Cases but not controls had a significant positive correlation between local cytokine gene expression and Fusobacterium abundance. Among cases, the correlation for local TNF-α and Fusobacterium was r = 0.33, p = 0.06 while it was 0.44, p = 0.01 for Fusobacterium and IL-10. These results support a link between the abundance of Fusobacterium in colonic mucosa and adenomas and suggest a possible role for mucosal inflammation in this process.


Hearing in the Juvenile Green Sea Turtle (Chelonia mydas): A Comparison of Underwater and Aerial Hearing Using Auditory Evoked Potentials.
Sea turtles spend much of their life in aquatic environments, but critical portions of their life cycle, such as nesting and hatching, occur in terrestrial environments, suggesting that it may be important for them to detect sounds in both air and water. In this study we compared underwater and aerial hearing sensitivities in five juvenile green sea turtles (Chelonia mydas) by measuring auditory evoked potential responses to tone pip stimuli. Green sea turtles detected acoustic stimuli in both media, responding to underwater stimuli between 50 and 1600 Hz and aerial stimuli between 50 and 800 Hz, with maximum sensitivity between 200 and 400 Hz underwater and 300 and 400 Hz in air. When underwater and aerial hearing sensitivities were compared in terms of pressure, green sea turtle aerial sound pressure thresholds were lower than underwater thresholds, however they detected a wider range of frequencies underwater. When thresholds were compared in terms of sound intensity, green sea turtle sound intensity level thresholds were 2-39 dB lower underwater particularly at frequencies below 400 Hz. Acoustic stimuli may provide important environmental cues for sea turtles. Further research is needed to determine how sea turtles behaviorally and physiologically respond to sounds in their environment.


Reduced-size porcine lung transplantation: long-term studies of pulmonary vascular resistance.
The use of isolated adult lobes for pediatric lung transplantation has recently been reported and could potentially help alleviate the profound pediatric donor lung shortage. However, the effect of chronic denervation on pulmonary vasculature of isolated mature lobar transplants is not well understood. Previously, we reported that chronic denervation of the immature porcine lobe results in abnormal pulmonary vascular compliance. We now present studies of long-term pulmonary hemodynamics in young pigs 12 weeks after transplantation of a reduced-size mature left lower lobe. Resting pulmonary vascular resistance of the transplanted mature lobes was similar to that of innervated lobes of age-matched controls. In addition, pulmonary vascular resistance of the transplanted mature lobes did not rise abnormally in response to increased flow caused by clamping the contralateral pulmonary artery. We conclude that denervation of the mature porcine lobe does not result in abnormal pulmonary vascular resistance. In addition, vascular compliance of reduced-size mature porcine lobar transplants is superior to that of denervated reimplanted immature lobes. These findings suggest a deleterious effect of denervation on pulmonary vascular development of the growing porcine lung.


Neurodiversity: Autism pride among mothers of children with autism spectrum disorders.
The neurodiversity movement takes an identity politics approach to autism spectrum disorders, proposing autism spectrum disorders as a positive "neuro-variation" to be approached only with interventions that assist individuals without changing them. This article explicates the concept of neurodiversity and places it within the context of autism spectrum disorders advocacy and treatments. It draws from fieldwork conducted in a midwestern urban center, from June through October 2008, with support groups for parents of children with autism spectrum disorders. Neurodiverse sentiments were identified within these groups, despite the pursuance of treatments to which some neurodiversity advocates might object. Therefore, although neurodiversity has influenced parents of children with autism spectrum disorders in this sample, its role as a medical advocacy group has not been fully realized. This article attempts to place neurodiversity in better conversation with advocates and medical professionals.


Strategy for radioactive waste disposal in crystalline rocks.
A strategy for waste disposal is proposed in which the repository would be situated in a crystalline rock mass beneath a blanket of sedimentary rocks whose ground-water flow characteristics are well understood. Such an approach exemplifies the concept of multiple barriers to the isolation of radioactive wastes from the biosphere. This strategy has the advantages that (i) ground-water flow within the sedimentary rocks can be investigated and modeled by conventional, well-under-stood theory and technology; (ii) under favorable circumstances, the flow system operates as an active barrier, so that a long migration path and extremely low flow rate to the biosphere can be assured; and (iii) since, in many locations, ground water is nonpotable, the possibility of future human intrusion can be minimized.


Longitudinal left ventricular systolic function is impaired in patients with coronary slow flow.
Slow coronary flow (SCF) is a well recognized clinical entity, characterized by delayed opacification of coronary arteries in the presence of normal coronary angiogram. There is currently no data evaluating myocardial systolic function in SCF phenomenon. This study was performed to evaluate regional and global systolic function using tissue Doppler imaging (TDI), strain (S) and strain rate imaging (SRI) in patients with slow coronary flow. A total of 35 patients with slow coronary flow and otherwise normal coronary arteries (mean age 48 +/- 7 years) (SCF group) and 21 patients with normal coronary angiograms (mean age 50 +/- 12 years) (control group) were included in the study. These patients were prospectively assessed for evaluation of regional and global left ventricular function by conventional echocardiography, systolic TDI, peak S, and peak systolic strain rates (SRs) There was a significant difference in peak SRs (-1.1 +/- 0.2 vs. -1.8 +/- 0.2 1/s, P < or = 0.0001) but similar in systolic TDI (42 +/- 20 vs. 44 +/- 21 mm/s, P = 0.77) and S (20.7 +/- 7.7 vs. 23.7 +/- 8.8, P = 0.14) between groups. SRs showed a good correlation with mean TIMI frame count (r = -0.80, P < or = 0.0001). As the number of coronary artery with SCF increased global strain rate decreased further. In case of one or two or three coronary artery with SCF global strain rates were 1.4 +/- 0.2; 1.1 +/- 0.3; 0.9 +/- 0.2 1/s, respectively, P < or = 0.0001. Although ejection fraction was preserved, global and regional strain rate were decreased in SCF. In brief, there is an impairment in longitudinal left ventricular systolic function in patients with SCF.


Where and why do conifer forests persist in refugia through multiple fire events?
Changing wildfire regimes are causing rapid shifts in forests worldwide. In particular, forested landscapes that burn repeatedly in relatively quick succession may be at risk of conversion when pre-fire vegetation cannot recover between fires. Fire refugia (areas that burn less frequently or severely than the surrounding landscape) support post-fire ecosystem recovery and the persistence of vulnerable species in fire-prone landscapes. Observed and projected fire-induced forest losses highlight the need to understand where and why forests persist in refugia through multiple fires. This research need is particularly acute in the Klamath-Siskiyou ecoregion of southwest Oregon and northwest California, USA, where expected increases in fire activity and climate warming may result in the loss of up to one-third of the region's conifer forests, which are the most diverse in western North America. Here, we leverage recent advances in fire progression mapping and weather interpolation, in conjunction with a novel application of satellite smoke imagery, to model the key controls on fire refugia occurrence and persistence through one, two, and three fire events over a 32-year period. Hotter-than-average fire weather was associated with lower refugia probability and higher fire severity. Refugia that persisted through three fire events appeared to be partially entrained by landscape features that offered protection from fire, suggesting that topographic variability may be an important stabilizing factor as forests pass through successive fire filters. In addition, smoke density strongly influenced fire effects, with fire refugia more likely to occur when smoke was moderate or dense in the morning, a relationship attributable to reduced incoming solar radiation resulting from smoke shading. Results from this study could inform management strategies designed to protect fire-resistant portions of biologically and topographically diverse landscapes.


Electronic Rapid Fitness Assessment Identifies Factors Associated with Adverse Early Postoperative Outcomes following Radical Cystectomy.
Frailty is associated with adverse outcomes following radical cystectomy. Prospective tools to identify factors affecting outcomes are needed. We describe a novel electronic rapid fitness assessment to evaluate geriatric patients undergoing radical cystectomy. Before undergoing radical cystectomy between February 2015 and February 2018, 80 patients older than age 75 years completed the electronic rapid fitness assessment and were perioperatively comanaged by the Geriatrics Service. Physical function and cognitive function over 12 domains were evaluated and an accumulated geriatric deficit score was compiled. Hospital length of stay, discharge disposition, unplanned intensive care unit admissions, urgent care visits, readmissions, complications and deaths were assessed. A total of 65 patients who underwent radical cystectomy for bladder cancer without concomitant procedures completed the assessment. Median age was 80 (77, 84) years and 52 (80%) were male. A higher proportion of patients with intensive care unit admission, urgent care visit and major complications had impairments identified within electronic rapid fitness assessment domains, including Timed Up and Go. Readmission rates were similar between patients with or without deficits identified. Higher accumulated geriatric deficit score was significantly associated with intensive care unit admission (p=0.035), death within 90 days (p=0.037) and discharge to other than home (p=0.0002). We demonstrated the feasibility of assessing fitness in patients older than 75 years undergoing radical cystectomy using a novel electronic fitness tool. Physical limitations and overall impairment corresponded to higher intensive care unit admission rates and adverse postoperative outcomes. Larger studies in less resourced environments are required to validate these findings.


Periodicity, synchronization and persistence in pre-vaccination measles.
We investigate the relationship between periodicity, synchronization and persistence of measles through simulations of geographical spread on the British Isles. We show that the establishment of areas of biennial periodicity depends on the interplay between human mobility and local population size and that locations undergoing biennial cycles tend to be, on average, synchronized in phase. We show however that occurrences of opposition of phase are actually quite common and correspond to stable dynamics. We also show that persistence is strictly related to circulation of the disease in the highly populated area of London and that this ensures survival of the disease even when human mobility drops to extremely low levels.


Exploring impacts of multi-year, community-based care programs for orphans and vulnerable children: a case study from Kenya.
The Community-Based Care for Orphans and Vulnerable Children (CBCO) program operated in Kenya during 2006-2010. In Eastern Province, the program provided support to approximately 3000 orphans and vulnerable children (OVC) living in 1500 households. A primary focus of the program was to support savings and loan associations composed of OVC caregivers (typically elderly women) to improve household and OVC welfare. Cross-sectional data were collected in 2011 from 1500 randomly selected households from 3 populations: program participants (CBCO group, n=500), households in the same villages as program participants but not in the program (the local-community-group = Group L, n=300), and households living in nearby villages where the program did not operate (the adjacent-community-group, Group A, n=700). Primary welfare outcomes evaluated are household food security, as measured by the Household Food Insecurity Access instrument, and OVC educational attainment. We compared outcomes between the CBCO and the subset of Group L not meeting program eligibility criteria (L-N) to investigate disparities within local communities. We compared outcomes between the CBCO group and the subset of Group A meeting eligibility criteria (A-E) to consider program impact. We compared outcomes between households not eligible for the program in the local and adjacent community groups (L-N and A-N) to consider if the adjacent communities are similar to the local communities. In May-June 2011, at the end of the OVC program, the majority of CBCO households continued to be severely food insecure, with rates similar to other households living in nearby communities. Participation rates in primary school are high, reflecting free primary education. Among the 18-22 year olds who were "children" during the program years, relatively few children completed secondary school across all study groups. Although the CBCO program likely provided useful services and benefits to program participants, disparities continued to exist in food security and educational outcomes between program participants and their non-OVC peers in the local community. Outcomes for CBCO households were similar to those observed for OVC households in adjacent communities.


Effect of protein source and soluble carbohydrate addition on rumen fermentation and lactation performance of Holstein cows.
Rumen in vitro and in vivo experiments were conducted to evaluate the effect of rumen undegradable protein and soluble carbohydrates on rumen ammonia N release and lactation performance of Holstein cows. In the in vitro experiment, freeze-dried annual ryegrass (Lolium multiflorum, LAM) pasture was supplemented 1:1 with ground corn-based grain supplements containing expeller or solvent soybean meal with sucrose or lactose supplements at 0, 2.5, or 5% of dry matter (DM). The ammonia release rate was slower with expeller compared with solvent soybean meal-supplemented diets. Sucrose supplementation at the 5% level lowered rumen ammonia concentrations, but lactose-fortification of grain supplements was without effect. In the in vivo study, 32 multiparous Holstein cows were blocked according to milk yield and randomly assigned to corn-based grain supplements containing 1) solvent soybean meal, 2) solvent soybean meal + 5% sucrose supplement, 3) expeller soybean meal, or 4) expeller soybean meal + 5% sucrose supplement. Grain supplements and fresh annual ryegrass were component fed at approximately a 1:1 grain to forage ratio (DM basis). Forage DM intake was higher for cows receiving solvent soybean meal supplemented grain supplements than those receiving expeller soybean meal (12.2 +/- 2.1 vs. 11.4 +/- 2.2 kg/d), but total DM intake was similar for all diets (22.8 +/- 2.9 kg/d). Fat-corrected milk yield was similar for all diets averaging 37.5, 38.2, 39.1, and 37.6 kg/d for diets 1 to 4, respectively. Rumen fermentation, milk urea nitrogen, and body condition were unaffected by supplements; however, cows fed grain supplement 1 utilized dietary energy more efficiently than cows offered the other dietary treatments. High dietary crude protein concentrations may have limited lactation response to rumen undegradable protein and sugar.


Harnessing the Electronic Health Record to Actively Support Providers with Guideline-Directed Telemetry Use.
Overuse of cardiac telemetry monitoring (telemetry) can lead to alarm fatigue, discomfort for patients, and unnecessary medical costs. Currently there are evidence-based recommendations describing appropriate telemetry use, but many providers are unaware of these guidelines. At our multihospital health system, our goal was to support providers in ordering telemetry on acute care in accordance with evidence-based guidelines and discontinuing telemetry when it was no longer medically indicated. We implemented a multipronged electronic health record (EHR) intervention at two academic medical centers, including: (1) an order set requiring providers to choose an indication for telemetry with a recommended duration based on American Heart Association guidelines; (2) an EHR-generated reminder page to the primary provider recommending telemetry discontinuation once the guideline-recommended duration for telemetry is exceeded; and (3) documentation of telemetry interpretation by telemetry technicians in the notes section of the EHR. To determine the impact of the intervention, we compared number of telemetry orders actively discontinued prior to discharge and telemetry duration 1 year pre- to 1 year post-intervention on acute care medicine services. We evaluated sustainability at years 2 and 3. Implementation of the EHR initiative resulted in a statistically significant increase in active discontinuation of telemetry orders prior to discharge: 15% (63.4-78.7%) at one site and 13% at the other (64.1-77.4%) with greater improvements on resident teams. Fewer acute care medicine telemetry orders were placed on medicine services across the system (1,503-1,305) despite an increase in admissions and the average duration of telemetry decreased at both sites (62 to 47 hours, p < 0.001 and 73 to 60, p < 0.001, respectively). Improvements were sustained 2 and 3 years after intervention. Our study showed that a low-cost, multipart, EHR-based intervention with active provider engagement and no additional education can decrease telemetry usage on acute care medicine services.


Biological activities of lipopolysaccharides are determined by the shape of their lipid A portion.
Lipopolysaccharide (LPS) represents a major virulence factor of Gram-negative bacteria ('endotoxin') that can cause septic shock in mammals including man. The lipid anchor of LPS to the outer membrane, lipid A, has a peculiar chemical structure, harbours the 'endotoxic principle' of LPS and is responsible for the expression of pathophysiological effects. Chemically modified lipid A can be endotoxically inactive, but may express strong antagonistic activity against LPS, a property that can be utilized in antisepsis treatment. We show here that these different biological activities are directly correlated with the molecular shape of lipid A. Only (hexaacyl) lipid A with a conical/concave shape, the cross-section of the hydrophobic region being larger than that of the hydrophilic region, exhibited strong interleukin-6 (IL-6)-inducing capacity. Most strikingly, a correlation between a cylindrical molecular shape of lipid A and antagonistic activity was established: IL-6 induction by enterobacterial LPS was inhibited by cylindrically shaped lipid A except for compounds with reduced headgroup charge. The antagonistic action is interpreted by assuming that lipid A molecules intercalate into the cytoplasmic membrane of mononuclear cells, and subsequently blocking of the putative signaling protein by the lipid A with cylindrical shape.


Mesh sacrocolpopexy compared with native tissue vaginal repair: a systematic review and meta-analysis.
To systematically review outcomes after mesh sacrocolpopexy compared with native tissue vaginal repairs in women with apical prolapse. We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov through June 4, 2012. For anatomic and functional analyses, we included studies comparing mesh sacrocolpopexy to native tissue vaginal repairs with at least 6 months follow-up. The primary outcome was anatomic "success" after surgery. Secondary outcomes were reoperation and symptom outcomes. We included large case series and comparative studies with shorter follow-up to increase power for adverse event analyses. Evidence quality was assessed with the Grades for Recommendation, Assessment, Development and Evaluation system. Meta-analyses were performed when at least three studies reported the same outcome. We included 13 comparative studies for anatomic success, reoperation, and symptom outcomes. Moderate-quality evidence supports improved anatomic outcomes after mesh sacrocolpopexy; very low-quality evidence shows no differences in reoperation between sacrocolpopexy and native tissue vaginal repairs. Evidence was insufficient regarding which procedures result in improved bladder or bowel symptoms. Low-quality evidence showed no differences in postoperative sexual function. Adverse event data were compiled and meta-analyzed from 79 studies. When including larger noncomparative studies, ileus or small bowel obstruction (2.7% compared with 0.2%, P<.01), mesh or suture complications (4.2% compared with 0.4%, P<.01), and thromboembolic phenomena (0.6% compared with 0.1%, P=.03) were more common after mesh sacrocolpopexy compared with native tissue vaginal repairs. When anatomic durability is a priority, we suggest that mesh sacrocolpopexy may be the preferred surgical option. When minimizing adverse events or reoperation is the priority, there is no strong evidence supporting one approach over the other.


Development of the Korean Practice Parameter for Adult Attention-Deficit/Hyperactivity Disorder.
Adult attention-deficit/hyperactivity disorder (ADHD) is an important mental health problem that needs resolution, especially considering the high rates of ADHD continuation from childhood to adolescence/adulthood and the high prevalence of ADHD in adults. Adults with ADHD have lifelong negative impacts and require close monitoring with long-term follow-up. Hence, the establishment of a Korean practice parameter for adult ADHD is necessary to minimize discontinuation of treatment and enable information sharing among Korean mental health professionals. The Korean practice parameter was developed using an evidence-based approach consisting of expert consensus survey coupled with literature review. According to the expert consensus survey, the most commonly used diagnostic methods were clinical psychiatric interview (20.66%) and self-report scales (19.25%) followed by attention (14.71%) and psychological tests (14.24%). Key evaluation instruments currently available in Korea are the World Health Organization Adult ADHD Self-Report Rating Scale, Korean Adult ADHD Rating Scale, Diagnostic Interview for ADHD in Adults, Barkley Deficits in Executive Functioning Scale for adults, Comprehensive Attention Test, Conners' Continuous Performance Test, and the subtests of Wechsler Adult Intelligence Scale, Digit Span and Letter-Number Sequencing. Although pharmacotherapy is recommended as the first-line of treatment for adult ADHD, we recommend that it be followed by a multimodal and multidisciplinary approach including psychoeducation, pharmacotherapy, cognitive behavior therapy and coaching. The Korean practice parameter introduces not only general information for the diagnosis and treatment of adult ADHD on a global scale, but also the process of diagnosis and treatment options tailored to the Korean population.


Indoor and outdoor air concentrations of volatile organic compounds and NO2 in schools of urban, industrial and rural areas in Central-Southern Spain.
Thirty two VOCs including alkanes, aromatic hydrocarbons, terpenes and carbonyl compounds together with NO2 were investigated in a kindergarten classroom, a primary classroom and the playground in 18 schools located in rural areas, an urban area (Ciudad Real) and an industrial area (Puertollano) in the province of Ciudad Real in central southern Spain. The most abundant pollutants at schools were the aldehydes formaldehyde and hexanal. After carbonyls, n-dodecane was the most abundant compound in the study areas. The NO2 concentrations were higher in the urban area, followed by industrial area and rural areas. For benzene, its concentration in the industrial area was significantly higher than in the urban and rural areas which reflects the magnitude of the contribution to the indoor air by petrochemical plant during the sampling period. Principal component analysis, indoor/outdoor ratios, multiple linear regressions and Spearman correlation coefficients were used to investigate the origin, the indoor pollutant determinants and to establish common sources between VOCs and NO2. Seven components were extracted from the application of PCA to the indoor measurements accounting for 77.5% of the total variance. The analysis of indoor/outdoor ratios and correlations demonstrated that sources in the indoor environment are prevailing for most of the investigated VOCs. Benzene and n-pentane have a major relevance as outdoor sources, while aldehydes, terpenes, alkanes and most aromatic hydrocarbons as indoor sources. For NO2, ethylbenzene and toluene both indoor and outdoor sources probably contributed to the measured concentrations. Finally, the results reported in this paper demonstrate that during the measuring period there were not great differences in the indoor air quality of the schools of the three study areas.


Prognosis of coma after therapeutic hypothermia: a prospective cohort study.
This study was designed to establish the reliability of neurologic examination, neuron-specific enolase (NSE), and median nerve somatosensory-evoked potentials (SEPs) to predict poor outcome in patients treated with mild hypothermia after cardiopulmonary resuscitation (CPR). This multicenter prospective cohort study included adult comatose patients admitted to the intensive care unit (ICU) after CPR and treated with hypothermia (32-34°C). False-positive rates (FPRs 1 - specificity) with their 95% confidence intervals (CIs) were calculated for pupillary light responses, corneal reflexes, and motor scores 72 hours after CPR; NSE levels at admission, 12 hours after reaching target temperature, and 36 hours and 48 hours after collapse; and SEPs during hypothermia and after rewarming. The primary outcome was poor outcome, defined as death, vegetative state, or severe disability (Glasgow Outcome Scale 1-3) after 6 months. Of 391 patients included, 53% had a poor outcome. Absent pupillary light responses (FPR 1; 95% CI, 0-7) or absent corneal reflexes (FPR 4; 95% CI, 1-13) 72 hours after CPR, and absent SEPs during hypothermia (FPR 3; 95% CI, 1-7) and after rewarming (FPR 0; 95% CI, 0-18) were reliable predictors. Motor scores 72 hours after CPR (FPR 10; 95% CI, 6-16) and NSE levels were not. In patients with persisting coma after CPR and therapeutic hypothermia, use of motor score or NSE, as recommended in current guidelines, could possibly lead to inappropriate withdrawal of treatment. Poor outcomes can reliably be predicted by testing brainstem reflexes 72 hours after CPR and performing SEP.


The solution-phase process of a g-C3N4/BiVO4 dyad to a large-area photoanode: interfacial synergy for highly efficient water oxidation.
The oxygen evolution reaction (OER) is the rate-limiting process for water splitting, and highly efficient large-area OER photoanodes have been considered as an essential part in photoelectrochemical water splitting reactors. The high hole-electron separation efficiency of photoanodes is highly required for real applications of photoanodes in sufficiently harvesting solar energy. Herein we show that the inactive g-C3N4 nanolayers can be self-assembled with BiVO4 into a highly coupled BV/CN dyad to significantly enhance the charge separation efficiency of BiVO4 photoelectrodes for the OER. The incident photon-to-current conversion efficiency (IPCE) of visible light (400 nm) provided by the scalable BV/CN-5 photoanode was estimated to be 50% at 1.23 V vs. RHE in 0.5 M Na2SO4 solution and significantly increased to 97% at a bias voltage of 1.6 V vs. RHE.


Autosomal recessive mitochondrial ataxic syndrome due to mitochondrial polymerase gamma mutations.
To investigate three families and one sporadic case with a recessively inherited ataxic syndrome. Clinical and genetic studies were performed in six individuals. Southern blotting and real time PCR were used to detect deletions of mtDNA and mutations in the POLG gene were identified using a combination of DHPLC and direct DNA sequencing. The patients have a distinctive, progressive disorder that starts with episodic symptoms such as migraine-like headache or epilepsy. Ataxia, which is a combination of central and peripheral disease, develops later as does ophthalmoplegia. The commonest form of epilepsy was focal and involved the occipital lobes. Myoclonus was common and patients have a high risk of status epilepticus. MRI typically shows signal changes in the central cerebellum, olivary nuclei, occipital cortex, and thalami. COX negative muscle fibers were found in four of six; in one patient these were rare and in another absent. Multiple mtDNA deletions were identified in all patients, although in two these were not apparent on Southern blotting and real time PCR was required to demonstrate the defect. Two families were homozygous for a previously described POLG mutation, G1399A (A467T). One family and the sporadic case had the same two new mutations, a G to C at position 1491 (Q497H) and a G to C at 2243 (W748S). Mutations in POLG cause a recessively inherited syndrome with episodic features and progressive ataxia. Characteristic changes on MRI are seen and although skeletal muscle may appear morphologically normal, multiple mtDNA deletions can be detected using real-time PCR.


A two-stage strategy to accommodate general patterns of confounding in the design of observational studies.
Accommodating general patterns of confounding in sample size/power calculations for observational studies is extremely challenging, both technically and scientifically. While employing previously implemented sample size/power tools is appealing, they typically ignore important aspects of the design/data structure. In this paper, we show that sample size/power calculations that ignore confounding can be much more unreliable than is conventionally thought; using real data from the US state of North Carolina, naive calculations yield sample size estimates that are half those obtained when confounding is appropriately acknowledged. Unfortunately, eliciting realistic design parameters for confounding mechanisms is difficult. To overcome this, we propose a novel two-stage strategy for observational study design that can accommodate arbitrary patterns of confounding. At the first stage, researchers establish bounds for power that facilitate the decision of whether or not to initiate the study. At the second stage, internal pilot data are used to estimate key scientific inputs that can be used to obtain realistic sample size/power. Our results indicate that the strategy is effective at replicating gold standard calculations based on knowing the true confounding mechanism. Finally, we show that consideration of the nature of confounding is a crucial aspect of the elicitation process; depending on whether the confounder is positively or negatively associated with the exposure of interest and outcome, naive power calculations can either under or overestimate the required sample size. Throughout, simulation is advocated as the only general means to obtain realistic estimates of statistical power; we describe, and provide in an R package, a simple algorithm for estimating power for a case-control study.


Regional specificity of the emotional-aversive response induced by carbachol in the cat brain: a quantitative mapping study.
In this paper, the emotional-aversive response induced by intracerebral injection of carbachol has been studied in cats by recording their vocalization as an index of emotional behavior. The carbachol-induced responses were quantitatively mapped in the basal forebrain and diencephalic regions using the cumulative time of the animal's vocalization as a measure of response. The areas inducing the emotional- aversive response extended along two axes: 1. longitudinally along the neuraxis, from the reticular formation through the hypothalamus to the rostro-basal forebrain; and 2. vertically along the fornix, from the mediobasal hypothalamus to the septal area. The highest magnitude of the response (vocalization time) was obtained from a strip of tissue extending from the septum and preoptic area to the dorsal perifornical area, the dorsomedial hypothalamic nucleus, the paraventricular nucleus and the periventricular stratum. The pattern of distribution of reactive and nonreactive sites showed anatomic specificity, with the highest sensitivity found within the close periventricular tissue of the third ventricle. It is suggested that carbachol mapping selectively delineates the muscarinic cholinoceptive portion of the aversive, emotional brain system.


[Multidrug-resistant Acinetobacter baumannii infection in respiratory intensive care unit].
Multidrug-resistant Acinetobacter boumannii is a challenge in the treatment and control of nosocomial infections. This retrospective study was aimed to investigate the prevalence of multidrug resistant A. boumannii in a respiratory intensive care unit (ICU), related risk factors and its impact on disease prognosis. Of 218 patients who were hospitalized in our ICU during the last two years; 37 (17%) patients (21 males, mean age 61.6 +/- 19.8 years) developed pneumonia and/or bacteremia due to multidrug-resistant A. baumannii. Previous antibiotic therapy was detected in 51.4% and hospitalization in 70.3% of the cases. Pneumonia (59.5%) was the most frequent cause of hospitalization and chronic obstructive pulmonary disease (21.6%) was the second one; 81.1% of patients had co-morbidity. Invasive mechanical ventilation was performed in 31 (83.7%) patients during the follow-up. Ventilator-associated pneumonia developed in 22 (59.5%) patients and bacteraemia in 9 (24.3%) patients. Multidrug-resistance was observed in 23 (62.2%) of patients. Highest rates of resistance (100%) was detected against piperacillin-tazobactam, ampicillin-sulbactam and ciprofloxacin, followed by imipenem and cefepime (78%), meropenem and ceftazidime (55%), cefoperazone-sulbactam (43%) and netilmicin (35.1). The rates of re-intubation and tracheotomy were higher in patients infected with A. boumannii compared to the control group (59.5% vs. 7.7%, p < 0.0001 and 21.6% vs. 3.9%, p = 0.001, respectively). There was no significant difference between two groups in terms of mortality, however, durations of ICU and hospital stays were longer in patients with multidrug-resistant A. baumannii infection than without infection (24.2 +/- 18.3 vs. 8.2 +/- 8.3 days, p < 0.001 and 33.3 +/- 19.8 vs. 15.4 +/- 11.4 days, p < 0.001, respectively). In conclusion, due to the high rates of drug-resistance in nosocomial A.baumannii isolates, the use of invasive procedures and durations of ICU and hospital stays exhibit an increasing trend.


Superiority of salt restriction over diuretics in reducing renal hypertrophy and injury in uninephrectomized SHR.
Spontaneously hypertensive rats (SHR) were uninephrectomized (UNX) at 6 wk of age and given either standard chow (CON), low-sodium chow (LSC), or standard chow and hydrochlorothiazide (HCTZ) added to the drinking water. Severe hypertension developed in all three groups. Forty-two weeks after UNX, proteinuria and glomerular sclerosis were significantly lower in LSC than in CON or HCTZ. The protective effect of salt restriction did not depend upon alterations in plasma renin concentration or glomerular hemodynamics. Micropuncture revealed that glomerular pressure was high in all three groups. Renal hypertrophy assessed by kidney weight, kidney-to-body weight ratio, glomerular volume, and glomerular capillary radius were reduced by salt restriction. These findings suggest that, in the setting of glomerular hypertension, hypertrophy promotes sclerosis. Salt restriction inhibits compensatory kidney growth and protects the kidney.


Characterization of the SPI-1 and Rsp type three secretion systems in Pseudomonas fluorescens F113.
Pseudomonas fluorescens F113 is a plant growth-promoting rhizobacterium (PGPR) isolated from the sugar beet rhizosphere. The recent annotation of the F113 genome sequence has revealed that this strain encodes a wide array of secretion systems, including two complete type three secretion systems (T3SSs) belonging to the Hrp1 and SPI-1 families. While Hrp1 T3SSs are frequently encoded in other P. fluorescens strains, the presence of a SPI-1 T3SS in a plant-beneficial bacterial strain was unexpected. In this work, the genetic organization and expression of these two T3SS loci have been analysed by a combination of transcriptional reporter fusions and transcriptome analyses. Overexpression of two transcriptional activators has shown a number of genes encoding putative T3 effectors. In addition, the influence of these two T3SSs during the interaction of P. fluorescens F113 with some bacterial predators was also assessed. Our data revealed that the transcriptional activator hilA is induced by amoeba and that the SPI-1 T3SS could potentially be involved in resistance to amoeboid grazing.


Sequence comparison of five polymerases (L proteins) of unsegmented negative-strand RNA viruses: theoretical assignment of functional domains.
The large (L) protein subunit of unsegmented negative-strand RNA virus polymerases is thought to be responsible for the majority of enzymic activities involved in viral transcription and replication. In order to gain insight into this multifunctional role we compared the deduced amino acid sequences of five L proteins of rhabdoviruses (vesicular stomatitis virus and rabies virus) or paramyxoviruses (Sendai virus, Newcastle disease virus and measles virus). Statistical analysis showed that they share an atypical amino acid usage, outlining the uniqueness of the negative-strand virus life style. Similarity studies between L proteins traced evolutionary relationships in partial disagreement with the present taxonomic arrangement of this group of viruses. The five L proteins exhibit a high degree of homology along most of their length, with strongly invariant amino acids embedded in conserved blocks separated by variable regions, suggesting a structure of concatenated functional domains. The most highly conserved central block contains the probable active site for RNA synthesis. We tentatively identified some other functional sites, distributed around this central core, that would naturally work together to assure the polymerase activity. This provides detailed guidelines for the future study of L proteins by site-directed mutagenesis.


Incidence and predictors of readmissions to non-index hospitals after transcatheter aortic valve replacement and the impact on in-hospital outcomes: From the nationwide readmission database.
Whether readmission to non-index hospitals (where the initial procedure was not performed) could result in adverse outcomes and increased utilization of healthcare resources compared with readmission to index hospitals after transcatheter aortic valve replacement (TAVR) remains unclear. From January 2012 to September 2015, a nationwide readmission database was queried to identify those who were older than 50 years and had endovascular TAVR, using the International Classification of Disease, 9th Revision, Clinical Modification code 35.05. Elective readmissions were excluded. In-hospital outcomes were compared between the index and non-index hospital readmissions. A multivariable logistic regression analysis was performed to identify predictors of non-index hospital readmissions. A total of 6808 readmissions were identified of which 2564 (37.7%) were readmitted to non-index hospitals. Residents at smaller counties, metropolitan non-teaching hospitals, or hospitals at large metropolitan areas were predictors of non-index readmissions. In-hospital mortality (adjusted odds ratio [aOR] 1.27, p = 0.20), acute myocardial infarction (aOR 0.83, p = 0.53), pacemaker placement (aOR 0.97, p = 0.90), acute kidney injury (aOR 0.98, p = 0.84), and stroke (aOR 1.03, p = 0.90) were similar between index and non-index readmissions but bleeding events requiring transfusions were more frequently observed in readmissions at non-index hospitals (aOR 1.32, p = 0.025). Hospital cost (15,410 dollars vs. 16,390 dollars, p = 0.25) and length of stay (5.70 days vs. 5.65 days, p = 0.85) were comparable between groups. Non-index readmissions post-TAVR was relatively common but did not result in increased hospital mortality or healthcare utilization. Our results are reassuring for TAVR recipients with limited access to index hospitals.


Sensory and motor deficits exist on the non-injured side of patients with unilateral tendon pain and disability--implications for central nervous system involvement: a systematic review with meta-analysis.
Tendinopathy manifests as activity-related tendon pain with associated motor and sensory impairments. Tendon tissue changes in animals present in injured as well as contralateral non-injured tendon. This review investigated evidence for bilateral sensory and motor system involvement in unilateral tendinopathy in humans. A comprehensive search of electronic databases, and reference lists using keywords relating to bilateral outcomes in unilateral tendinopathy was undertaken. Study quality was rated with the Epidemiological Appraisal Instrument and meta-analyses carried out where appropriate. Analysis focused on comparison of measures in the non-symptomatic side of patients against pain-free controls. The search revealed 5791 studies, of which 20 were included (117 detailed reviews, 25 met criteria). There were 17 studies of lateral epicondylalgia (LE) and one each for patellar, Achilles and rotator cuff tendinopathy. Studies of LE were available for meta-analysis revealing the following weighted pooled mean deficits: pressure pain thresholds (-144.3 kPa; 95% CI -169.2 to -119.2 p<0.001), heat pain thresholds (-1.2°C; 95% CI -2.1 to -0.2, p<0.001), cold pain thresholds (3.1°C; 95% CI 1.8 to 4.4, p<0.001) and reaction time (37.8 ms; 95% CI 24.8 to 50.7, p<0.001). Deficits in sensory and motor systems present bilaterally in unilateral tendinopathy. This implies potential central nervous system involvement. This indicates that rehabilitation should consider the contralateral side of patients. Research of unilateral tendinopathy needs to consider comparison against pain-free controls in addition to the contralateral side to gain a complete understanding of sensory and motor features.


Acrylamide-derived DNA adducts in human peripheral blood mononuclear cell DNA: Correlation with body mass.
Acrylamide (AA) is a carcinogen formed during thermal food processing and can cause tumors in rodents while its carcinogenic potency in humans is unclear. Metabolic conversion of AA leads to glycidamide (GA) forming N7-GA-guanine (N7-GA-Gua) as the major DNA adduct in rodents while no such adducts were found in human tissues so far. In a cohort of 56 healthy volunteers adduct levels were determined in peripheral blood mononuclear cell (PBMC) DNA and anthropometric, dietary, and biochemical parameters were measured or inquired using a questionnaire. In the majority of PBMC DNA samples the levels found were above one adduct/108 nucleosides not being correlated to dietary habits including coffee consumption, or to blood glucose levels or hemoglobin HbA1c. However, adduct levels were significantly correlated with the body mass index (BMI) and showed a continuous increase over three BMI classes. Our findings indicate a background of AA-derived DNA adducts present in humans in PBMC related to body mass rather than to certain dietary or lifestyle factors.


To Protect or to Kill? Environmental Contingent Self-Worth Moderates Death Prime Effects on Animal-Based Attitudes.
Lifshin et al. found that death primes increased support for killing animals, suggesting that the killing of animals serves a terror management function. The present research adds to this by suggesting that protecting animals can also serve a terror management function when people see such behaviors as culturally valuable. In three studies (N = 765), environmental contingent self-worth (ECSW) moderated the effect of death primes on attitudes toward animals. Attitudes toward animals also mediated the effect of a death prime on increased power-based invulnerability for those with low ECSW and decreased power-based invulnerability for those with high ECSW (Study 3). Finally, we found little support that death primes influenced beliefs regarding human-animal superiority (Study 1 and 2) or similarity (Study 2). Our findings therefore provide partial support for past terror management research and further the understanding regarding how to promote more benevolent human-animal relations.


Association of the pneumococcal pilus with certain capsular serotypes but not with increased virulence.
The recent discovery of a mobile genetic element encoding a pilus-like structure in Streptococcus pneumoniae and the demonstration of a role for the pilus in virulence in mice have led to the proposal of the use of the pilus as a candidate pneumococcal vaccine. We examined the frequency of occurrence of the pneumococcal pilus, as determined by the presence of the rrgC gene, and analyzed its association with virulence, capsular serotypes, and multilocus sequence types in the American Indian pneumococcal collection and isolates of S. pneumoniae from blood cultures collected at Children's Hospital Boston. Overall, 21.4% of strains in the American Indian collection had the rrgC gene, but there was no difference between isolates obtained from the nasopharynx and those obtained from sterile sites (blood or cerebrospinal fluid). Vaccine-type strains were significantly more likely than non-vaccine-type strains to have this pilus gene (P < 0.001). Among isolates with identical multilocus sequence types, there was a high concordance (95%) between the multilocus sequence type and the presence or the absence of rrgC. Finally, in the era of the pneumococcal conjugate vaccine, the frequency of rrgC in isolates from Children's Hospital Boston has decreased significantly (42.8% before 2000 versus 21.3% after 2000; P = 0.019). Therefore, our data show that the pilus is present in a minority of strains and is associated with certain serotypes and that its frequency has been reduced by the conjugate pneumococcal vaccine.


Multiple Indicator Cluster Surveys: Delivering Robust Data on Children and Women across the Globe.
This article provides an overview of the Multiple Indicator Cluster Surveys (MICS) as a data source. MICS-one of the largest household survey programs focused on children and women-has covered 116 countries, many over several rounds of surveys producing trend data. Data are collected on a range of indicators for children, adolescents, women, and in recent years, men. Topics include fertility, mortality, contraceptive use, unmet need, maternal and newborn health, female genital mutilation, menstrual hygiene management, child illness and treatment, and child development and nutrition, among others. The surveys are cross-sectional and use multistage probability designs to develop representative samples of households at the national and subnational levels. Survey interviews are conducted with: a household respondent who provides data on the household status; women and men aged 15-49 who provide current status and retrospective data on themselves; and mothers (or caregivers) who provide data on children under age 18. Data can be compared across countries and time for the most part, provide a wealth of indicators across research fields, and are open access. Data can be accessed on the MICS website where users are granted access to the MICS datasets for research purposes.


High-quality genome assembly of the soybean fungal pathogen Cercospora kikuchii.
Plant diseases caused by the Cercospora genus of ascomycete fungi are a major concern for commercial agricultural practices. Several Cercospora species can affect soybeans, such as Cercospora kikuchii which causes soybean leaf blight. Speciation in Cercospora on soybean has not been adequately studied. Some cryptic groups of Cercospora also cause diseases on soybean. Moreover, it has been known C. kikuchii population genetic structure is different between countries. Consequently, further genomic information could help to elucidate the covert differentiation of Cercospora diseases in soybean. Here, we report for the first time, a chromosome-level genome assembly for C. kikuchii. The genome assembly of 9 contigs was 34.44 Mb and the N50 was 4.19 Mb. Based on ab initio gene prediction, several candidates for pathogenicity-related genes, including 242 genes for putative effectors, 55 secondary metabolite gene clusters, and 399 carbohydrate-active enzyme genes were identified. The genome sequence and the features described in this study provide a solid foundation for comparative and evolutionary genomic analysis for Cercospora species that cause soybean diseases worldwide.


ABCB5 Identifies Immunoregulatory Dermal Cells.
Cell-based strategies represent a new frontier in the treatment of immune-mediated disorders. However, the paucity of markers for isolation of molecularly defined immunomodulatory cell populations poses a barrier to this field. Here, we show that ATP-binding cassette member B5 (ABCB5) identifies dermal immunoregulatory cells (DIRCs) capable of exerting therapeutic immunoregulatory functions through engagement of programmed cell death 1 (PD-1). Purified Abcb5(+) DIRCs suppressed T cell proliferation, evaded immune rejection, homed to recipient immune tissues, and induced Tregs in vivo. In fully major-histocompatibility-complex-mismatched cardiac allotransplantation models, allogeneic DIRCs significantly prolonged allograft survival. Blockade of DIRC-expressed PD-1 reversed the inhibitory effects of DIRCs on T cell activation, inhibited DIRC-dependent Treg induction, and attenuated DIRC-induced prolongation of cardiac allograft survival, indicating that DIRC immunoregulatory function is mediated, at least in part, through PD-1. Our results identify ABCB5(+) DIRCs as a distinct immunoregulatory cell population and suggest promising roles of this expandable cell subset in cellular immunotherapy.


Functional proteomics of Arabidopsis thaliana guard cells uncovers new stomatal signaling pathways.
We isolated a total of 3 x 10(8) guard cell protoplasts from 22,000 Arabidopsis thaliana plants and identified 1734 unique proteins using three complementary proteomic methods: protein spot identification from broad and narrow pH range two-dimensional (2D) gels, and 2D liquid chromatography-matrix assisted laser desorption/ionization multidimensional protein identification technology. This extensive single-cell-type proteome includes 336 proteins not previously represented in transcriptome analyses of guard cells and 52 proteins classified as signaling proteins by Gene Ontology analysis, of which only two have been previously assessed in the context of guard cell function. THIOGLUCOSIDE GLUCOHYDROLASE1 (TGG1), a myrosinase that catalyzes the production of toxic isothiocyanates from glucosinolates, showed striking abundance in the guard cell proteome. tgg1 mutants were hyposensitive to abscisic acid (ABA) inhibition of guard cell inward K(+) channels and stomatal opening, revealing that the glucosinolate-myrosinase system, previously identified as a defense against biotic invaders, is required for key ABA responses of guard cells. Our results also suggest a mechanism whereby exposure to abiotic stresses may enhance plant defense against subsequent biotic stressors and exemplify how enhanced knowledge of the signaling networks of a specific cell type can be gained by proteomics approaches.


Optimization and design of oligonucleotide setup for strand displacement amplification.
Several advantages of strand displacement amplification (SDA) as an all-purpose DNA amplification reaction are due to it isothermal mechanism. The major problem of isothermal amplification mechanism is the accumulation of non-predictable byproduct especially for longer incubation time and low concentrations of initial template DNA. New theoretical strategies to tackle the difficulties regarding the specificity of the reaction are experimentally verified. Besides improving the reaction conditions, the stringency of primer hybridization can be distinctly improved by computer based sequence prediction algorithms based on the thermodynamic stability of DNA hybrid a described by the partition function of the hybridization reaction. An alternative SDA mechanism, with sequences developed by this means is also investigated.


Physicochemical and physiological properties of cholylsarcosine. A potential replacement detergent for bile acid deficiency states in the small intestine.
The properties of cholylsarcosine (the synthetic N-acyl conjugate of cholic acid with sarcosine [N-methylglycine]) were examined to determine its suitability as a bile acid replacement agent for conditions of bile acid deficiency in the small intestine, which causes fat malabsorption. Previous studies in rodents had shown that the compound was well transported by the liver and ileum and underwent neither deconjugation nor dehydroxylation during enterohepatic cycling. By 1H-nuclear magnetic resonance, cholylsarcosine was found to exist in dilute aqueous solution as an almost equimolar mixture of two geometric isomers--cis and trans (around the amide bond)--in contrast to cholylglycine, which was present entirely in the trans form. The critical micellization concentration was 11 mmol/liter, similar to that of cholylglycine (10 mmol/liter). By nonaqueous titrimetry, the pKa' of cholylsarcosine was 3.7, only slightly lower than that of cholylglycine (3.9). Cholylsarcosine was poorly soluble below pH 3.7, but highly soluble above pH 4. In vitro, cholylsarcosine behaved as cholylglycine with respect to promoting lipolysis by lipase/colipase. There was little difference between cholylsarcosine and cholylglycine in their solubilization of an equimolar mixture of oleic acid, oleate, and monoolein (designed to simulate digestive products of triglyceride) or in their solubilization of monooleyl-glycerol alone. When a [3H]triolein emulsion with either cholylsarcosine or cholyltaurine was infused intraduodenally in biliary fistula rats, recovery of 3H in lymph was 52 +/- 10% (mean +/- SD) for cholylsarcosine and 52 +/- 11% for cholyltaurine. When perfused into the colon of the anesthetized rabbit, cholylsarcosine (5 mmol/liter) did not influence water absorption or permeability to erythritol, in contrast to chenodeoxycholate, which induced vigorous water secretion and caused erythritol loss. We conclude that cholylsarcosine possesses the physicochemical and physiological properties required for a suitable bile acid replacement in deficiency states.


[Changes in endocrine profile of workers in pulp and paper plant.]
Examination covered 245 individuals and included characteristics of endocrine state of pulp and paper plant workers over 2011-2012, in comparison with data from 1990, as well as comparison with reference groups of male workers with no contact with chemical'industry in Arkhangelsk. Findings are both in main and reference groups general decrease in levels of cortisol, thyroxin;progesterone, testosterone, insulin, somatotropin and increased serum level of estradiol. With that, inside both groups, reliable tendencies to increased levels of cortisol, thyroxin, insulin, SSH and lower concentration of progesterone in the pulp and paper plant workers vs. the reference group members. Positive tendency was absence of abnormal concentrations of insulin, SSH and lower frequency of high cortisol levels in the pulp and paper plant workers nowadays.


Palm-up test and range of motion in flexion and external rotation provide best correlation with disability and perceived pain in patients with shoulder complaints.
The aim of this study was to find a reliable set of clinical tests to predict pain and disability in patients with shoulder pain. Shoulder pain is the second most frequent musculoskeletal complaint in the primary care setting and has a great impact in work and leisure activities. Patient reported outcomes measuring pain and disability are available, but they are time-consuming, often biased by psychological and sociological factors and depend on patient collaboration. This was an observational, cross-sectional study, including patients with shoulder pain aged 18 to 70 years. Patients filled in the questionnaires Disabilities of the Arm, Shoulder and Hand outcome measure (DASH) and Shoulder Pain and Disability Index (SPADI) pain scale. A Visual Analogue Scale (VAS) for current pain was applied and sociodemographic and clinical data were collected. Physical examination included the Jobe, Neer and palm-up signs, range of motion (ROM) of shoulder abduction, flexion and rotation (internal and external), both active and passive. An independent t-test to compare differences between groups and the Spearman's coefficient for evaluation of bivariate correlation were used. Linear regression analysis was applied to relevant predictors. Tests were two-tailed and p values < 0.05 were considered significant. A total of 127 patients were included. Female patients and those with a positive Jobe, Neer or palm-up tests, complaints on dominant side, no leisure activity involving shoulder effort, a history of previous shoulder tendinopathy or taking analgesics had significantly higher DASH scores. Age and all range of motion variables significantly correlated with DASH scores. A linear regression model with six dependent variables (Palm-up test, range of motion in active flexion and external rotation, age, gender and complaints on dominant side) produced the highest correlation (R = 0.665), explaining 44% of the variance of DASH score. A model based on few physical examination items and individual objective data like age, gender and dominancy, can help predict disability and perceived pain in shoulder disorders. Palm-up test and range of motion in active flexion, abduction and external rotation showed best correlation with the outcome, but abduction was found redundant for the obtained prediction model.


The incidence of concha bullosa and its relationship to nasal septal deviation and paranasal sinus disease.
The incidence of middle turbinate pneumatization, or concha bullosa, has been well described in the literature. However, to our knowledge, no study has evaluated concha bullosa in relation to nasal septal deviation. We sought to analyze the incidence of concha bullosa and any correlation with nasal septal deviation and paranasal sinus disease. Three neuroradiologists retrospectively reviewed findings of 1095 consecutive paranasal sinus CT studies conducted between 2001 and 2002. All examinations were performed for evaluation of a symptom referable to the sinonasal region. Paranasal sinus inflammatory disease was identified and graded as mild, moderate, or severe. Sphenoid, ethmoid, maxillary, and frontal sinuses were each graded separately on both sides. If a concha bullosa was present, it was graded in size as small, moderate, or large. If bilateral concha were present, sizes were compared and when one was larger, it was identified as dominant. When nasal septal deviation was present, it was graded as mild, moderate, or severe. The direction of nasal septal deviation was identified as the face of the convex surface. There was a clear association between the presence of a unilateral concha, or a dominant concha (in the case of bilateral concha), and the presence of nasal septal deviation (P < .0001). Moreover, there was a significant relationship between the presence of concha bullosa and deviation of the nasal septal to the contralateral side (P < .0001). This inverse association was present regardless of the size of the concha bullosa or degree of septal deviation. In every case, there was some preservation of air channels between the dominant concha and the nasal septum. Seventy-three percent of patients with concha bullosa had paranasal sinus inflammatory disease; 78% of patients without concha bullosa also had some form of inflammatory disease. Concha bullosa is a common anatomic variant. There is a strong association between the presence of a concha bullosa and contralateral deviation of the nasal septum. Nasal septal deviation away from the dominant concha, with preserved adjacent air channels, suggests that the deviation is not a direct result of mass effect from the concha. No increased incidence of paranasal sinus disease exists in patients with concha bullosa.


[Anesthetic management of a patient with Freeman-Sheldon syndrome].
The Freeman-Sheldon syndrome is a rare congenital myopathy and dysplasia that results in deformity of the face, hands, and feet. We describe here some problems in general anesthesia from the anesthetic management point of view. An 8-year-old girl with Freeman-Sheldon syndrome underwent surgery under general anesthesia for the correction of lip deformity and microstomia. Patients with this syndrome may present anesthetic problems involving difficulties in endotracheal intubation due to microstomia, micrognathia and neck rigidity, as well as postoperative respiratory complications and problems that relate to myogenetic morphology and myofunctional abnormalities. Preoperatively, we analyzed X-ray cephalograms to evaluate the difficulty of endotracheal intubation. Fiberscopic endotracheal intubation was performed; the time required was 55 minutes. On recovery from anesthesia and after becoming fully responsive, she was extubated in the operating room without any complications. Postoperative recovery was uneventful. Patients with Freeman-Sheldon syndrome should be managed by good preanesthetic preparation, and attention should be paid to postoperative respiratory complications due to the use of muscle relaxants and to securing intravenous access.


Successful treatment of stage III neuroblastoma based on prospective biologic staging: a Children's Cancer Group study.
To identify a biologically favorable and unfavorable subset of patients with Evans stage III neuroblastoma and to determine whether treatment stratification would improve the event-free survival (EFS) for high-risk patients and maintain excellent EFS for the lower-risk patients. Risk stratification was performed by age, MYCN gene copy number, Shimada histopathologic classification, and serum ferritin level. Lower-risk patients were treated on the less intensive Children's Cancer Group (CCG)-3881, whereas high-risk patients were treated on CCG-3891, which included more intensive multimodality therapy and, in some cases, autologous bone marrow transplantation (ABMT). Of 228 Evans stage III patients entered onto the study, 92% also met the definition of International Neuroblastoma Staging System (INSS) stage 3. One hundred forty-three patients met the lower-risk criteria, which included 89 patients less than 1 year of age and 54 patients 1 year of age or greater, and favorable biology, whereas 85 patients were 1 year of age or greater and biologically unfavorable. Biologically unfavorable patients 1 year of age or greater who underwent gross surgical resection had improved survival, whereas the outcome of infants or biologically favorable older patients did not change according to resection. The EFS rate at 4 years was 100% for the patients with favorable biology of any age, 90% for those less than 1 year of age but with at least one unfavorable characteristic, and 54% for Evans stage III patients 1 year of age or greater with unfavorable biology. Age, ferritin level, MYCN copy number, Shimada histopathology, primary site, and intraspinal extension were significant univariate prognostic factors for all patients, but only MYCN copy number and age were independent factors in multivariate analyses. The excellent survival of the biologically favorable group and the historically improved EFS of the biologically unfavorable group suggest that biologic staging should be used to define the prognosis and treatment of stage III neuroblastoma.


Emergent bistability: effects of additive and multiplicative noise.
Positive feedback and cooperativity in the regulation of gene expression are generally considered to be necessary for obtaining bistable expression states. Recently, a novel mechanism of bistability termed emergent bistability has been proposed which involves only positive feedback and no cooperativity in the regulation. An additional positive feedback loop is effectively generated due to the inhibition of cellular growth by the synthesized proteins. The mechanism, demonstrated for a synthetic circuit, may be prevalent in natural systems also as some recent experimental results appear to suggest. In this paper, we study the effects of additive and multiplicative noise on the dynamics governing emergent bistability. The calculational scheme employed is based on the Langevin and Fokker-Planck formalisms. The steady state probability distributions of protein levels and the mean first passage times are computed for different noise strengths and system parameters. In the region of bistability, the bimodal probability distribution is shown to be a linear combination of a lognormal and a Gaussian distribution. The variances of the individual distributions and the relative weights of the distributions are further calculated for varying noise strengths and system parameters. The experimental relevance of the model results is also pointed out.


Clostridium guangxiense sp. nov. and Clostridium neuense sp. nov., two phylogenetically closely related hydrogen-producing species isolated from lake sediment.
Two novel anaerobic, mesophilic, biohydrogen-producing bacteria, designated strains ZGM211T and G1T, were isolated from lake sediment. 16S rRNA and ATP synthase beta subunit (atpD) gene sequences and phylogenetic analysis of strains ZGM211T and G1T revealed an affiliation to the genus Clostridium sensu stricto (cluster I of the clostridia), with Clostridium acetobutylicum as the closest characterized species, showing the same sequence similarity of 96.4 % to the type strain (98.9 % between the two isolates). Cells of the two strains were rod shaped. Growth occurred at 20-45 °C, pH 4.0-8.0 and NaCl concentrations up to 2 % (w/v). Grown on glucose, the main fermentation products were H2, CO2, acetate and butyrate. The major fatty acids were C14 : 0 and C16 : 0. The DNA G+C contents of strains ZGM211T and G1T were 40.7 and 41.5 mol%, respectively. Based on phenotypic, chemotaxonomic and phylogenetic differences, strains ZGM211T (=CICC 24070T=BCRC 80950T) and G1T (=CICC 24069T=BCRC 80949T) are proposed as the type strains of novel species of the genus Clostridium with the names Clostridium guangxiense sp. nov. and Clostridium neuense sp. nov., respectively.


[Mechanism of action of vinpocetine].
Cavinton was introduced into the clinical practice some twenty years ago in Hungary for the treatment of cerebrovascular disorders and related symptoms. Since then, its active ingredient, vinpocetine, beside its therapeutical utilization, has become a reference compound in the pharmacological research of cognitive deficits caused by hypoxia and ischaemia as well as in the cellular and biochemical investigations related to cyclic nucleotides. In this review a survey is given on the experimental data obtained with vinpocetine and an attempt is made to outline the drug's mechanism of action. Early experiments with vinpocetine indicated five main pharmacological and biochemical actions: (1) selective enhancement of the brain circulation and oxygen utilization without significant alteration in parameters of systemic circulation, (2) increased tolerance of the brain toward hypoxia and ischemia, (3) anticonvulsant activity, (4) inhibitory effect on phosphodiesterase (PDE) enzyme and (5) improvement of rheological properties of the blood and inhibition of aggregation of thrombocytes. Later studies in various laboratories confirmed the above effects and clearly demonstrated that vinpocetine offers significant and direct neuroprotection both under in vitro and in vivo conditions. Evidence has been obtained that neuroprotective action vinpocetine is related to the inhibition of operation of voltage dependent neuronal Na(+)-channels, indirect inhibition of some molecular cascades initiated by the rise of intracellular Ca(2+)-levels and, to a lesser extent, inhibition of adenosine reuptake. Vinpocetine has been shown to be selective inhibitor of Ca(2+)-calmodulin dependent cGMP-PDE. It is assumed that this inhibition enhances intracellular a GMP levels in the vascular smooth muscle leading to reduced resistance of cerebral vessels and increase of cerebral flow. This effect might also beneficially contribute to the neuroprotective action.


Antibodies targeting human OX40 expand effector T cells and block inducible and natural regulatory T cell function.
Current cancer vaccines induce tumor-specific T cell responses without sustained tumor regression because immunosuppressive elements within the tumor induce exhaustion of effector T cells and infiltration of immune-suppressive regulatory T cells (Tregs). Therefore, much effort has been made to generate agonistic Abs targeting members of the TNFR superfamily, such as OX40, 4-1BB, and GITR, expressed on effector T cells and Tregs, to reinvigorate T cell effector function and block Treg-suppressive function. In this article, we describe the development of a panel of anti-human OX40 agonistic mouse mAbs that could promote effector CD4(+) and CD8(+) T cell proliferation, inhibit the induction of CD4(+) IL-10 -producing type 1 regulatory T cells, inhibit the expansion of ICOS(+)IL-10(+) Tregs, inhibit TGF-β-induced FOXP3 expression on naive CD4(+) T cells, and block natural Treg-suppressive function. We humanized two anti-human OX40 mAb clones, and they retained the potency of their parental clones. These Abs should provide broad opportunities for potential combination therapy to treat a wide realm of cancers and preventative vaccines against infectious diseases.


Intravenous catheter complications in the hand and forearm.
We studied the complications of peripheral intravenous (i.v.) catheters in the hand and forearm in a teaching hospital over a 3-year period. The records of 67 patients who developed i.v. catheter-related complications were reviewed. The most common sites for developing complications in order of frequency were the forearm, hand, wrist, and antecubital fossa. There were 56 minor and 11 major complications. More than 50% of minor complications occurred in the hand and wrist, and more than 50% of major complications occurred in the hand. In 68% of minor complications, the patients were aged 50 years or older and 68% were women. Minor complications comprised 26 intravenous infiltrations, 23 cases of thrombophlebitis, and 7 cases of cellulitis. Ninety percent of major complication patients were aged 50 or older and 82% were women. Major complications included septic thrombophlebitis in three; hematomas resulting in skin necrosis in two; and infiltration related complications in six, resulting in skin necrosis in two, compressive nerve lesions in two, digital stiffness in one, and compartment syndrome in one. Ten patients with major complications were over the age of 50 years and nine were women. Two patients receiving anticoagulation developed large dorsal subcutaneous space hematomas. Chemotherapeutic agents contributed to two minor complications and one major complication. The hand is a common site for minor and major i.v. catheter complications. Women and older patients are more susceptible to these complications. Peripheral i.v. line complications are not uncommon and can result in morbidity and increased health care costs from prolonged hospitalization, extended use of i.v. antibiotic therapy, and surgical intervention.


The Width of Invasion in Malignant Melanoma Is a Novel Prognostic Feature That Accounts for Outcome Better Than Breslow Thickness.
Breslow thickness (BT) is the cornerstone of malignant melanoma staging. However, to our knowledge no-one has ever assessed the horizontal width of invasion, measured microscopically, as a prognostic feature. This was investigated as a prognostic feature in this study. A retrospective cohort of 1329 melanoma cases was collected from patients presenting to a UK teaching hospital from January 1, 2004, to December 31, 2014. The main outcome was overall survival (OS). We found that width was associated with OS in multivariable analysis (hazard ratio=1.05, 95% confidence interval: 1.03-1.07, P<0.001) and was similarly significant for melanoma-specific survival and metastasis-free survival. Its presence rendered BT nonsignificant. The width was significantly associated with OS after adjustment for American Joint Committee on Cancer (AJCC), version 8 clinical tumor stage (hazard ratio=1.05, 95% confidence interval: 1.03-1.07, P<0.001), and bootstrap validation showed only slight model optimism. Similar associations were seen for melanoma-specific survival and metastasis-free survival. However, the combination of invasive width and BT did not account for the outcome as well as another novel histologic feature, tumor area, which was measured using the calculated tumor area method. In conclusion, this study is the first investigation of a novel histologic feature, invasive melanoma width, and demonstrates its strong independent association with outcome.


Temperature regulates the initiation of chasmothecia in powdery mildew of strawberry.
The formation of chasmothecia by the strawberry powdery mildew pathogen (Podosphaera aphanis) is widespread but often sporadic throughout the range of strawberry cultivation. In some production regions, notably in warmer climates, chasmothecia are reportedly rare. We confirmed that the pathogen is heterothallic, and that initiation of chasmothecia is not only dependent upon the presence of isolates of both mating types but also largely suppressed at temperatures >13°C. Compared with incubation at a constant temperature of 25°C, progressively more chasmothecia were initiated when temperatures were decreased to 13°C for progressively longer times. At lower temperatures, production of chasmothecia was associated with a decline in but not total cessation of conidial formation, and pairings of compatible isolates sporulated abundantly at 25°C. We developed mating-type markers specific to P. aphanis and used these to confirm the presence of both mating types in populations that had not yet initiated chasmothecia. The geographic discontinuity of chasmothecia production and the sporadic and seemingly unpredictable appearance of chasmothecia in P. aphanis are possibly due to the combined influence of heterothallism and suppression of chasmothecia formation by high temperatures.


Reasoning and concurrent timing: a study of the mechanisms underlying the effect of emotion on reasoning.
Negative emotions typically have an adverse effect on reasoning, especially analytic or logical reasoning. This effect can be explained using an attentional framework in which emotion detracts limited-capacity cognitive resources which are required for reasoning. Another possibility is that the effect of emotion on reasoning is mediated by arousal, as previous research has shown that physiological arousal can be associated with decreased reasoning performance. In this research, we used a dual-task paradigm combining a syllogistic reasoning task and a time production task. Prospective timing allows to disentangle the effects of attention and arousal: time productions should lengthen if emotion takes up cognitive resources that are therefore not available for timing, whereas time productions should shorten if emotional reasoning results from increased arousal. Results from two experiments confirm the adverse impact of emotion on logical reasoning performance. Reasoning about emotional contents led to lengthened time productions, which suggests that the capture of limited cognitive resources is the main factor accounting for the adverse effect of emotion on reasoning and not arousal.