Regional personality assessment through social media language.
We explore the personality of counties as assessed through linguistic patterns on social media. Such studies were previously limited by the cost and feasibility of large-scale surveys; however, language-based computational models applied to large social media datasets now allow for large-scale personality assessment. We applied a language-based assessment of the five factor model of personality to 6,064,267 U.S. Twitter users. We aggregated the Twitter-based personality scores to 2,041 counties and compared to political, economic, social, and health outcomes measured through surveys and by government agencies. There was significant personality variation across counties. Openness to experience was higher on the coasts, conscientiousness was uniformly spread, extraversion was higher in southern states, agreeableness was higher in western states, and emotional stability was highest in the south. Across 13 outcomes, language-based personality estimates replicated patterns that have been observed in individual-level and geographic studies. This includes higher Republican vote share in less agreeable counties and increased life satisfaction in more conscientious counties. Results suggest that regions vary in their personality and that these differences can be studied through computational linguistic analysis of social media. Furthermore, these methods may be used to explore other psychological constructs across geographies.


The role of the principle of double effect in ethics education at US medical schools and its potential impact on pain management at the end of life.
Because opioids can suppress respiratory drive, the principle of double effect (PDE) has been used to justify their use for terminally ill patients. Recent studies, however, suggest that the risk of respiratory depression in typical end-of-life (EOL) situations may be overstated and that heightened concern for this rare occurrence can lead to inadequate treatment of pain. The purpose of this study is to examine the role of the PDE in medical school ethics education, with specific reference to its potential impact on pain management at EOL. After obtaining institutional review board approval, an electronic survey was sent to ethics educators at every allopathic medical school in the USA. One-third of ethics educators felt that opioids were 'likely' to cause significant respiratory depression that could hasten death. Educators' opinions of opioid effects did not influence their view of the relevance of the PDE, with approximately 70% deeming it relevant to EOL care. Only 15% of ethics educators believed that associating the PDE with opioid use might discourage clinicians from optimally treating pain, out of concern for respiratory depression. This study demonstrates that a significant minority of ethics educators believe, contrary to current evidence, that opioids are 'likely' to cause significant respiratory depression that could hasten death in terminally ill patients. Yet, many of those who do not feel this is likely still rely on the PDE to justify this possibility, potentially (and unknowingly) contributing to clinical misperceptions and underutilisation of opioids at EOL.


Molecular basis of the interactions of the Nogo-66 receptor and its homolog NgR2 with myelin-associated glycoprotein: development of NgROMNI-Fc, a novel antagonist of CNS myelin inhibition.
Myelin-associated glycoprotein (MAG) is a sialic acid-binding Ig-family lectin that functions in neuronal growth inhibition and stabilization of axon-glia interactions. The ectodomain of MAG is comprised of five Ig-like domains and uses neuronal cell-type-specific mechanisms to signal growth inhibition. We show that the first three Ig-like domains of MAG bind with high affinity and in a sialic acid-dependent manner to the Nogo-66 receptor-1 (NgR1) and its homolog NgR2. Domains Ig3-Ig5 of MAG are sufficient to inhibit neurite outgrowth but fail to associate with NgR1 or NgR2. Nogo receptors are sialoglycoproteins comprised of 8.5 canonical leucine-rich repeats (LRR) flanked by LRR N-terminal (NT) and C-terminal (CT)-cap domains. The LRR cluster is connected through a stalk region to a membrane lipid anchor. The CT-cap domain and stalk region of NgR2, but not NgR1, are sufficient for MAG binding, and when expressed in neurons, exhibit constitutive growth inhibitory activity. The LRR cluster of NgR1 supports binding of Nogo-66, OMgp, and MAG. Deletion of disulfide loop Cys(309)-Cys(336) of NgR1 selectively increases its affinity for Nogo-66 and OMgp. A chimeric Nogo receptor variant (NgR(OMNI)) in which Cys(309)-Cys(336) is deleted and followed by a 13 aa MAG-binding motif of the NgR2 stalk, shows superior binding of OMgp, Nogo-66, and MAG compared with wild-type NgR1 or NgR2. Soluble NgR(OMNI) (NgR(OMNI)-Fc) binds strongly to membrane-bound inhibitors and promotes neurite outgrowth on both MAG and CNS myelin substrates. Thus, NgR(OMNI)-Fc may offer therapeutic opportunities following nervous system injury or disease where myelin inhibits neuronal regeneration.


Blending Emotions and Cross-Modality in Sonic Seasoning: Towards Greater Applicability in the Design of Multisensory Food Experiences.
Sonic seasoning refers to the way in which music can influence multisensory tasting experiences. To date, the majority of the research on sonic seasoning has been conducted in Europe or the USA, typically in a within-participants experimental context. In the present study, we assessed the applicability of sonic seasoning in a large-scale between-participants setting in Asia. A sample of 1611 participants tasted one sample of chocolate while listening to a song that evoked a specific combination of cross-modal and emotional consequences. The results revealed that the music's emotional character had a more prominent effect than its cross-modally corresponding attributes on the multisensory tasting experience. Participants expressed a higher buying intention for the chocolate and rated it as having a softer texture when listening to mainly positive (as compared to mainly negative) music. The chocolates were rated as having a more intense flavor amongst those participants listening to 'softer' as compared to 'harder' music. Therefore, the present study demonstrates that music is capable of triggering a combination of specific cross-modal and emotional effects in the multisensory tasting experience of a chocolate.


Cooler butterflies lay larger eggs: developmental plasticity versus acclimation.
We use a full factorial design to investigate the effects of maternal and paternal developmental temperature, as well as female oviposition temperature, on egg size in the butterfly Bicyclus anynana. Butterflies were raised at two different temperatures and mated in four possible sex-by-parental-temperature crosses. The mated females were randomly divided between high and low oviposition temperatures. On the first day after assigning the females to different temperatures, only female developmental temperature affected egg size. Females reared at the lower temperature laid larger eggs than those reared at a higher temperature. When eggs were measured again after an acclimation period of 10 days, egg size was principally determined by the prevailing temperature during oviposition, with females ovipositing at a lower temperature laying larger eggs. In contrast to widely used assumptions, the effects of developmental temperature were largely reversible. Male developmental temperature did not affect egg size in either of the measurements. Overall, developmental plasticity and acclimation in the adult stage resulted in very similar patterns of egg size plasticity. Consequently, we argue that the most important question when testing the significance of acclamatory changes is not at which stage a given plasticity is induced, but rather whether plastic responses to environmental change are adaptive or merely physiological constraints.


Leukaemia complicating treatment for Hodgkin's disease: the experience of the British National Lymphoma Investigation.
To determine the incidence of and risk factors for the development of secondary acute leukaemia and myelodysplasia in patients treated in British National Lymphoma Investigation's studies of Hodgkin's disease since 1970. 2676 Patients entered into Hodgkin's disease studies between February 1970 and November 1986. Data accrued up to November 1988 were analysed, ensuring a minimum follow up period of two years. Retrospective analysis of multicentre trial data by case-control and life table methods. 17 Cases of secondary leukaemia were recorded in this group of 2676 patients, giving an overall risk at 15 years of 1.7%. The risks of leukaemia after chemotherapy alone and chemotherapy with radiotherapy were not significantly different. The risk of leukaemia increased sharply with the amount of treatment given as measured by the number of attempts at treatment. The 15 year risks of leukaemia were 0.2%, 2.3%, and 8.1% for patients receiving one, two, or three or more attempts at treatment. The highest risk, 22.8% at 15 years, was observed in patients treated with lomustine (CCNU), and a case-control study suggested that this was an independent risk factor. The risk of secondary leukaemia was largely related to the overall quantity of treatment, although exposure to lomustine seemed to be an important risk factor. Treatment with both drugs and radiation was not more leukaemogenic than treatment with drugs alone. The greatest risk of secondary leukaemia was seen in multiply treated patients who were unlikely to be cured of Hodgkin's disease. Avoidance of secondary leukaemia should be a minor factor in the choice of treatment for Hodgkin's disease.


Conditional repair by locally switching the thermal healing capability of dynamic covalent polymers with light.
Healable materials could play an important role in reducing the environmental footprint of our modern technological society through extending the life cycles of consumer products and constructions. However, as most healing processes are carried out by heat alone, the ability to heal damage generally kills the parent material's thermal and mechanical properties. Here we present a dynamic covalent polymer network whose thermal healing ability can be switched 'on' and 'off' on demand by light, thereby providing local control over repair while retaining the advantageous macroscopic properties of static polymer networks. We employ a photoswitchable furan-based crosslinker, which reacts with short and mobile maleimide-substituted poly(lauryl methacrylate) chains forming strong covalent bonds while simultaneously allowing the reversible, spatiotemporally resolved control over thermally induced de- and re-crosslinking. We reason that our system can be adapted to more complex materials and has the potential to impact applications in responsive coatings, photolithography and microfabrication.


Burden of disease of people with epilepsy during an optimized diagnostic trajectory: costs and quality of life.
Diagnosing epilepsy can be lengthy and stressful, potentially leading to increased use of healthcare resources and a reduction in quality of life. This study aims to determine cost and quality of life before and after an optimized diagnostic procedure for people suspected of having epilepsy from a societal perspective with a follow-up of 12 months. In addition, this study aims to differentiate between people diagnosed with epilepsy during the follow-up of the study and the people who are diagnosed as not having epilepsy or for whom diagnosis is still uncertain. A questionnaire regarding the use of healthcare resources was used accompanied by the EQ-5D-3 L. Multiple imputations by chained equations with predictive mean matching was used to account for missing data. To investigate the uncertainty of the results, non-parametric bootstrapped (1000 times) was used. In total, 116 people were included in the study. Total average costs per patient made in the previous 3 months had decreased from €4594 before the optimized diagnostic trajectory to €2609 in the 12 months after the optimized diagnostic trajectory. Healthcare costs were the largest expense group (52-66%) and had decreased significantly from baseline measurement to 12 months after baseline (€2395 vs €1581). Productivity costs had decreased from €1367 to €442 per 3 months. Total annual costs were similar between people diagnosed with epilepsy during the follow-up of the study and the people who are diagnosed as not having epilepsy or for whom diagnosis is still uncertain. Quality of Life had significantly increased over the course of 12 months from 0.80 to 0.84 (Dutch tariff). This study indicates that an optimized diagnostic trajectory has positively influenced the use of healthcare resources and the quality of life in people with epilepsy. As chronic care patients make diverse costs, future research should identify the long-term costs after an optimized diagnostic trajectory for patients with epilepsy, possibly identifying patients who are at high risk of becoming high-cost users in the future for early intervention.


Role of PHGG as a dietary fiber: a review article.
Functional and metabolic effects of dietary fiber are recognized by the scientific, clinical and nutritional experts. Dietary fiber plays a very significant role in modifying the intestinal microbiota, exerting prebiotic effects such as stimulating the growth and/or function of beneficial intestinal microorganisms. Changes in the gut microbiota composition are classically considered as one of the many factors involved in the pathogenesis of either inflammatory bowel disease or irritable bowel syndrome. The use of particular food products with a prebiotic effect has thus been tested in clinical trials with the objective to improve the clinical activity and well-being of patients with such disorders. Partially Hydrolyzed Guar Gum (PHGG) is a natural dietary fiber (Benefibra™, Novartis CH Italy): it is a white powder, water-soluble, colorless and transparent in water solution and almost tasteless. PHGG is stable and soluble at various pH levels commonly found in foods as well as resistant to heat, acid, salt, high pressure and digestive enzymes. Low viscosity of PHGG provides a distinct advantage for the use of fiber in enteral feeding products to be administered through feeding tubes. It has been studied in adults, both healthy volunteers and patients, in different disorders such as constipation, irritable bowel syndrome (IBS), enteral nutrition, small intestine bacterial overgrowth (SIBO) and, very recently, in children suffering from functional abdominal pain according to the Rome III Criteria definition for functional gastrointestinal disorders (FGIDs). This review takes stock of the situation concerning what is known to date on PHGG as dietary fiber, in order to give the health care professionals, such as gastroenterologists, dieticians and general practitioners, a complete overview on its intrinsic characteristics, preclinical and clinical evaluations, uses in different situations as supportive therapy in the management of the main intestinal functional disorders both in adults and in children. All the papers on PHGG, published from the early 1990s of the Last Century to the Year 2013, have been considered. All types of publications have been included. PubMed, Medline, Ovid were the main sources adopted for data retrieving. PHGG has been studied in both animals and humans; its safety is well known and several clinical uses are well established. Concerning the modulation of metabolism in human, very little has been done to date and the studies have been focused, for the most part, on the functional diseases: PHGG has been proved to be useful in treating both IBS -C and D symptoms, not only in adults but also in children; data on constipation are relatively scarce and what can be deduced from the Literature is that the high concentration of fiber gives the PHGG the possibility of being used effectively in acceptable dosages (up to 22 g/day) even in situations such as chronic constipation. The use in clinical nutrition has revealed the flexibility of the compound which, owing to its peculiar characteristics, does not gel and remains liquid, PHGG can be used successfully in patients in enteral nutrition lowering the incidence of diarrhea. New open horizons can be glimpsed for SIBO treatment, lowering or maximizing the antibiotics use. Not all the fibers are the same: this is a fact. Promoting the specific knowledge of their characteristics is very important if healthcare professionals want to give their patients the best options for functional gastrointestinal disorders or nutritional needs. PHGG (Benefiber™ Novartis CH) has been proved to be safe and effective in promoting gut health.


Development of phytophotodermatitis in two cases related to Plantago lanceolata.
Plantago lanceolata, also known as snake's tongue, is a perennial herbaceous plant from the family Plantaginaceae. It is a species widely distributed both in Turkey and all over the world. Today, its fresh leaves are still used to soothe and suppress cough, externally for wound healing and draining abscesses. Phytophotodermatitis (PPD) is a dermal photosensitive reaction induced by the contact to or oral intake of a plant and subsequent exposure to sunlight. Its acute course is called phototoxic. In this paper, two cases developed phototoxic reaction with the consumption of Plantago lanceolata and subsequent exposure to the sunlight. These cases were presented since such effect of the plant has not been known previously and there is no resembling case in the literature.


Venous Thromboembolism and Cerebrovascular Events in Patients with Giant Cell Arteritis: A Population-Based Retrospective Cohort Study.
To investigate the incidence of venous thromboembolism (VTE) and cerebrovascular events in a community-based incidence cohort of patients with giant cell arteritis (GCA) compared to the general population. A population-based inception cohort of patients with incident GCA between January 1, 1950 and December 31, 2009 in Olmsted County, Minnesota and a cohort of non-GCA subjects from the same population were assembled and followed until December 31, 2013. Confirmed VTE and cerebrovascular events were identified through direct medical record review. The study population included 244 patients with GCA with a mean ± SD age at diagnosis of 76.2 ± 8.2 years (79% women) and an average length of follow-up of 10.2 ± 6.8 years. Compared to non-GCA subjects of similar age and sex, patients diagnosed with GCA had a higher incidence (%) of amaurosis fugax (cumulative incidence ± SE: 2.1 ± 0.9 versus 0, respectively; p = 0.014) but similar rates of stroke, transient ischemic attack (TIA), and VTE. Among patients with GCA, neither baseline characteristics nor laboratory parameters at diagnosis reliably predicted risk of VTE or cerebrovascular events. In this population-based study, the incidence of VTE, stroke and TIA was similar in patients with GCA compared to non-GCA subjects.


Autism from a biometric perspective.
The aim of this pilot study was to test autistic children, siblings and their parents using a biometric device based on the gas discharge visualization (GDV) technique in order to assess their psycho-emotional and physiological functional state based on the activity of the autonomic nervous system. We hypothesize that the biometric assessment based on GDV will enable us: (1) to evaluate some specific features associated with autism spectrum disorder (ASD) as well as to compare autistic children to their siblings and to controls; (2) to analyze the differences in individual values of parents of autistic children versus parents of normal children. Out of total of 48 acupuncture points present on ten fingertips of both hands and associated to organs/organ systems, autistic children differed significantly from controls (p < 0.05) in 36 (images without filter) and 12 (images with filter), siblings differed significantly from controls (p < 0.05) in 12 (images without filter) and seven (images with filter), autistic children differed significantly (p < 0.05) from siblings in eight (images without filter) and one (images with filter), fathers of autistic children differed significantly (p < 0.05) from controls in 14 (images without filter) and three (images with filter) and mothers of autistic children differed significantly (p < 0.05) from controls in five (images without filter) and nine (images with filter) acupuncture points. All compared groups have shown significant difference on both psycho-emotional (images without filter) and physiological (images with filter) levels. However, the differences between autistic children and controls expressed on psycho-emotional level were the most significant as compared to the other groups. Therefore, the activity of the sympathetic autonomic nervous system is significantly altered in children with autism. The biometric method based on GDV is a promising step in autism research that may lead towards creating a disease profile and identify unique signature/biomarker for autism. Further work should involve more participants in order to augment our findings.


Selective targeting of perivascular macrophages for clearance of beta-amyloid in cerebral amyloid angiopathy.
Cerebral amyloid angiopathy (CAA), the deposition of beta-amyloid (Abeta) peptides in leptomeningeal and cortical blood vessels, affects the majority of patients with Alzheimer's disease (AD). Evidence suggests that vascular amyloid deposits may result from impaired clearance of neuronal Abeta along perivascular spaces. We investigated the role of perivascular macrophages in regulating CAA severity in the TgCRND8 mouse model of AD. Depletion of perivascular macrophages significantly increased the number of thioflavin S-positive cortical blood vessels. ELISA confirmed that this increase was underscored by elevations in total vascular Abeta(42) levels. Conversely, stimulation of perivascular macrophage turnover reduced cerebral CAA load, an effect that was not mediated through clearance by microglia or astrocytes. These results highlight a function for the physiological role of perivascular macrophages in the regulation of CAA and suggest that selective targeting of perivascular macrophage activation might constitute a therapeutic strategy to clear vascular amyloid.


Anxiety and health-related quality of life among patients with low-tumor burden non-Hodgkin lymphoma randomly assigned to two different rituximab dosing regimens: results from ECOG trial E4402 (RESORT).
The purpose of this study was to compare illness-related anxiety among participants in the Rituximab Extended Schedule or Retreatment Trial (RESORT) randomly assigned to maintenance rituximab (MR) versus rituximab re-treatment (RR). A secondary objective was to examine whether the superiority of MR versus RR on anxiety depended on illness-related coping style. Patients (N = 253) completed patient-reported outcome (PRO) measures at random assignment to MR or RR (baseline); at 3, 6, 12, 24, 36, and 48 months after random assignment; and at rituximab failure. PRO measures assessed illness-related anxiety and coping style, and secondary end points including general anxiety, worry and interference with emotional well-being, depression, and health-related quality of life (HRQoL). Patients were classified as using an active or avoidant illness-related coping style. Independent sample t tests and linear mixed-effects models were used to identify treatment arm differences on PRO end points and differences based on coping style. Illness-related anxiety was comparable between treatment arms at all time points (P > .05), regardless of coping style (active or avoidant). Illness-related anxiety and general anxiety significantly decreased over time on both arms. HRQoL scores were relatively stable and did not change significantly from baseline for both arms. An avoidant coping style was associated with significantly higher anxiety (18% and 13% exceeded clinical cutoff points at baseline and 6 months, respectively) and poorer HRQoL compared with an active coping style (P < .001), regardless of treatment arm assignment. Surveillance until RR at progression was not associated with increased anxiety compared with MR, regardless of coping style. Avoidant coping was associated with higher anxiety and poorer HRQoL.


Microphysical Properties of Tropical Tropopause Layer Cirrus.
Pervasive cirrus clouds in the tropical tropopause layer (TTL) play an important role in determining the composition of stratospheric air through dehydration of tropospheric air entering the stratosphere. This dehydration affects Earth's energy budget and climate, yet uncertainties remain regarding the microphysical processes that govern TTL cirrus. TTL cirrus were sampled with the NASA Global Hawk UAV for over 30 hr in the Western Pacific in 2014 during the Airborne Tropical TRopopause EXperiment. In situ measurements by a Fast Cloud Droplet Probe and Hawkeye probe (combination Fast Cloud Droplet Probe, Two-Dimensional Stereo optical array probe, and Cloud Particle Imager) provided particle concentrations and sizing between 1- and 1,280-μm diameter and high resolution images for habit identification. We present the variability in ice concentrations, size distributions, and habits as functions of temperature, altitude, and time since convective influence. Observed ice particles were predominantly small and quasi-spheroidal in shape, with the percentage of quasi-spheroids increasing with decreasing temperature. In comparison to the large fraction of the population consisting of quasi-spheroids, faceted habits (columns, plates, rosettes, and budding rosettes) constituted a smaller percentage of the overall population and exhibited the opposite correlation with temperature. The trend of higher percentages of faceted crystals occurring at warmer temperatures may be due to diffusional growth or aggregation as particles descend through cloud, and/or the more rapid diffusional growth rate at warmer temperatures. Sampling was typically well away from deep convection, however, and very few aggregates were observed, so the trend of higher percentages of faceted habits is likely attributable to diffusional growth.


MRI signature in a novel mouse model of genetically induced adult oligodendrocyte cell death.
Two general pathological processes contribute to multiple sclerosis (MS): acute inflammation and degeneration. While magnetic resonance imaging (MRI) is highly sensitive in detecting abnormalities related to acute inflammation both clinically and in animal models of experimental autoimmune encephalomyelitis (EAE), the correlation of these readouts with acute and future disabilities has been found rather weak. This illustrates the need for imaging techniques addressing neurodegenerative processes associated with MS. In the present work we evaluated the sensitivity of different MRI techniques (T(2) mapping, macrophage tracking based on labeling cells in vivo by ultrasmall particles of iron oxide (USPIO), diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI)) to detect histopathological changes in a novel animal model making use of intrinsic, temporally and spatially controlled triggering of oligodendrocyte cell death. This mouse model allows studying the MRI signature associated to neurodegenerative processes of MS in the absence of adaptive inflammatory components that appear to be foremost in the EAE models. Our results revealed pronounced T(2) hyperintensities in brain stem and cerebellar structures, which we attribute to structural alteration of white matter by pronounced vacuolation. Brain areas were found devoid of significant macrophage infiltration in line with the absence of a peripheral inflammatory response. The significant decrease in diffusion anisotropy derived from DTI measures in these structures is mainly caused by a pronounced decrease in diffusivity parallel to the fiber indicative of axonal damage. Triggering of oligodendrocyte ablation did not translate into a significant increase in radial diffusivity. Only minor decreases in MT ratio have been observed, which is attributed to inefficient removal of myelin debris.


Emulating Human Tissues and Organs: A Bioprinting Perspective Toward Personalized Medicine.
The lack of in vitro tissue and organ models capable of mimicking human physiology severely hinders the development and clinical translation of therapies and drugs with higher in vivo efficacy. Bioprinting allow us to fill this gap and generate 3D tissue analogues with complex functional and structural organization through the precise spatial positioning of multiple materials and cells. In this review, we report the latest developments in terms of bioprinting technologies for the manufacturing of cellular constructs with particular emphasis on material extrusion, jetting, and vat photopolymerization. We then describe the different base polymers employed in the formulation of bioinks for bioprinting and examine the strategies used to tailor their properties according to both processability and tissue maturation requirements. By relating function to organization in human development, we examine the potential of pluripotent stem cells in the context of bioprinting toward a new generation of tissue models for personalized medicine. We also highlight the most relevant attempts to engineer artificial models for the study of human organogenesis, disease, and drug screening. Finally, we discuss the most pressing challenges, opportunities, and future prospects in the field of bioprinting for tissue engineering (TE) and regenerative medicine (RM).


The sul1 gene in Stenotrophomonas maltophilia with high-level resistance to trimethoprim/sulfamethoxazole.
Emerging resistance to trimethoprim/sulfamethoxazole (SXT) poses a serious threat to the treatment of Stenotrophomonas maltophilia infections. We determined the prevalence and molecular characteristics of acquired SXT resistance in recent clinical S. maltophilia isolates obtained from Korea. A total of 252 clinical isolates of S. maltophilia were collected from 10 university hospitals in Korea between 2009 and 2010. Antimicrobial susceptibility was determined by using the CLSI agar dilution method. The sul1, sul2, and sul3 genes, integrons, insertion sequence common region (ISCR) elements, and dfrA genes were detected using PCR. The presence of the sul1 gene and integrons was confirmed through sequence analysis. Among the 32 SXT-resistant isolates, sul1 was detected in 23 isolates (72%), all of which demonstrated high-level resistance (≥64 mg/L) to SXT. The sul1 gene (varying in size and structure) was linked to class 1 integrons in 15 of the 23 isolates (65%) harboring this gene. None of the SXT-susceptible isolates or the SXT-resistant isolates with a minimum inhibitory concentration of 4 and 8 mg/L were positive for sul1. Moreover, the sul2, sul3, and dfrA genes or the ISCR elements were not detected. The sul1 gene may play an important role in the high-level SXT resistance observed in S. maltophilia.


Biogenesis and function of fibrillin assemblies.
Fibrillin-1 and fibrillin-2 are large cysteine-rich glycoproteins that serve two key physiological functions: as supporting structures that impart tissue integrity and as regulators of signaling events that instruct cell performance. The structural role of fibrillins is exerted through the temporal and hierarchical assembly of microfibrils and elastic fibers, whereas the instructive role reflects the ability of fibrillins to sequester transforming growth factor beta (TGFbeta) and bone morphogenetic protein (BMP) complexes in the extracellular matrix. Characterization of fibrillin mutations in human patients and in genetically engineered mice has demonstrated that perturbation of either function manifests in disease. More generally, these studies have indicated that fibrillins are integral components of a broader biological network of extracellular, cell surface, and signaling molecules that orchestrate morphogenetic and homeostatic programs in multiple organ systems. They have also suggested that the relative composition of fibrillin-rich microfibrils imparts contextual specificity to TGFbeta and BMP signaling by concentrating the ligands locally so as to regulate cell differentiation within a spatial context during organ formation (positive regulation) and by restricting their bioavailability so as to modulate cell performance in a timely fashion during tissue remodeling/repair (negative regulation). Correlative evidence suggests functional coupling of the cell-directed assembly of microfibrils and targeting of TGFbeta and BMP complexes to fibrillins. Hence, the emerging view is that fibrillin-rich microfibrils are molecular integrators of structural and instructive signals, with TGFbeta and BMPs as the nodal points that convert extracellular inputs into discrete and context-dependent cellular responses.


Deletion of a Peptidylprolyl Isomerase Gene Results in the Inability of Caldicellulosiruptor bescii To Grow on Crystalline Cellulose without Affecting Protein Glycosylation or Growth on Soluble Substrates.
Caldicellulosiruptor bescii secretes a large number of complementary multifunctional enzymes with unique activities for biomass deconstruction. The most abundant enzymes in the C. bescii secretome are found in a unique gene cluster containing a glycosyl transferase (GT39) and a putative peptidyl prolyl cis-trans isomerase. Deletion of the glycosyl transferase in this cluster resulted in loss of detectable protein glycosylation in C. bescii, and its activity has been shown to be responsible for the glycosylation of the proline-threonine rich linkers found in many of the multifunctional cellulases. The presence of a putative peptidyl prolyl cis-trans isomerase within this gene cluster suggested that it might also play a role in cellulase modification. Here, we identify this gene as a putative prsA prolyl cis-trans isomerase. Deletion of prsA2 leads to the inability of C. bescii to grow on insoluble substrates such as Avicel, the model cellulose substrate, while exhibiting no differences in phenotype with the wild-type strain on soluble substrates. Finally, we provide evidence that the prsA2 gene is likely needed to increase solubility of multifunctional cellulases and that this unique gene cluster was likely acquired by members of the Caldicellulosiruptor genus with a group of genes to optimize the production and activity of multifunctional cellulases.IMPORTANCECaldicellulosiruptor has the ability to digest complex plant biomass without pretreatment and have been engineered to convert biomass, a sustainable, carbon neutral substrate, to fuels. Their strategy for deconstructing plant cell walls relies on an interesting class of cellulases consisting of multiple catalytic modules connected by linker regions and carbohydrate binding modules. The best studied of these enzymes, CelA, has a unique deconstruction mechanism. CelA is located in a cluster of genes that likely allows for optimal expression, secretion, and activity. One of the genes in this cluster is a putative isomerase that modifies the CelA protein. In higher eukaryotes, these isomerases are essential for the proper folding of glycoproteins in the endoplasmic reticulum, but little is known about the role of isomerization in cellulase activity. We show that the stability and activity of CelA is dependent on the activity of this isomerase.


Surgical correction of epiblepharon using thermal cauterization of the orbital septum and lash-rotating sutures.
Epiblepharon is a congenital eyelid anomaly frequently encountered in Asian infants and children. The purpose of this study was to describe the surgical technique of epiblepharon correction by applying both lash-rotating sutures in the inferior tarsus and the subcutaneous tissue of the upper skin flap and thermal cauterization in the septum. A retrospective, interventional study was performed on 75 patients who underwent surgical correction of epiblepharon between August 2006 and July 2007 by 1 surgeon. The upper skin incisional line was just below the eyelash line, and the delineated ellipse extended from just lateral to the punctum to the site of lash inversion. Dissection was carried out between the tarsal plate and orbital septum and the skin-pretarsal and preseptal orbicularis oculi muscle flap, thus exposing the tarsal plate and orbital septum. Thermal cauterization was applied to the orbital septum to create a cicatricial barrier adhesion between the preseptal orbicularis oculi muscle and the septum to minimize vertical overriding of the orbicularis oculi muscle. Three to 4 interrupted sutures were placed in the inferior tarsus and the subcutaneous tissue of the upper skin flap to rotate the direction of the lashes. The small amount of pretarsal orbicularis oculi muscle and redundant skin overlying the lower lid margin were removed. A total of 150 eyes (75 patients) were followed for 24.1 weeks (range, 4-12 months). Patients ranged in age from 2 to 13 years (median age, 7.3 years). All patients were diagnosed with bilateral epiblepharon, and surgery was performed on both eyelids. After a mean follow-up period of 14.1 weeks, no patients had recurrence, and all patients had good cosmetic results. Symptoms disappeared in all patients. There were no cases of lid retraction, wound dehiscence, or ectropion. Thermal cauterization of the orbital septum and lash-rotating sutures were very useful and effective for treating epiblepharon.


Associations of Biomechanical Properties of the Cornea With Environmental and Metabolic Factors in an Elderly Population: The ALIENOR Study.
The purpose of this study was to assess the associations of biomechanical properties of the cornea with metabolic and environmental factors in an elderly population. The ALIENOR (Antioxydants, Lipides Essentiels, Nutrition, and Maladies OculaiRes) study is a population-based study. In 2009-2010, 624 subjects, aged 74 years or more, underwent an eye examination, including intraocular pressure (IOP), central corneal thickness (CCT), and biomechanical properties of the cornea measurements using the Ocular Response Analyzer. Socio-demographic, lifestyle, and medical history data were collected using standardized questionnaires. Mean lifetime ambient ultraviolet (UV) exposure was estimated using residential history and statistics of UV radiation at each location using the Eurosun UV database. Mean age was 82.2 ± 4.3 years. Mean corneal hysteresis (CH), corneal resistance factor (CRF), and CCT were 9.4 ± 1.9, 9.8 ± 1.9 mm Hg, and 551.6 ± 36.8 μm, respectively. In the multivariate analysis, CH and CRF values were significantly lower in subjects older than 80 years (-0.56; 95% confidence interval [CI]: -0.89; -0.24); P < 0.001 and -0.48; 95% CI: -0.75;-0.20; P < 0.001, respectively), in subjects having higher ambient UV exposure (-0.50; 95% CI: -0.88; -0.12; P < 0.01; and -0.46; 95% CI: -0.78; -0.13); P < 0.05, respectively), and in subjects with high plasma LDL cholesterol (CH: -0.46; 95% CI: -0.86; -0.03; P < 0.05; and CRF: -0.37; 95% CI: -0.72; -0.008; P < 0.05). Central corneal thickness was significantly higher in former smokers than in never smokers (+11.01; 95% CI: 0.48; 21.55; P < 0.05) and was not significantly associated with age, ambient UV exposure, diabetes, or LDL cholesterol. Biomechanical properties of the cornea are modified by metabolic and lifetime environmental factors, especially UV exposure. The manner these factors may influence onset and progression of ocular diseases or IOP measurements need further investigation.


The Q Exactive HF, a Benchtop mass spectrometer with a pre-filter, high-performance quadrupole and an ultra-high-field Orbitrap analyzer.
The quadrupole Orbitrap mass spectrometer (Q Exactive) made a powerful proteomics instrument available in a benchtop format. It significantly boosted the number of proteins analyzable per hour and has now evolved into a proteomics analysis workhorse for many laboratories. Here we describe the Q Exactive Plus and Q Exactive HF mass spectrometers, which feature several innovations in comparison to the original Q Exactive instrument. A low-resolution pre-filter has been implemented within the injection flatapole, preventing unwanted ions from entering deep into the system, and thereby increasing its robustness. A new segmented quadrupole, with higher fidelity of isolation efficiency over a wide range of isolation windows, provides an almost 2-fold improvement of transmission at narrow isolation widths. Additionally, the Q Exactive HF has a compact Orbitrap analyzer, leading to higher field strength and almost doubling the resolution at the same transient times. With its very fast isolation and fragmentation capabilities, the instrument achieves overall cycle times of 1 s for a top 15 to 20 higher energy collisional dissociation method. We demonstrate the identification of 5000 proteins in standard 90-min gradients of tryptic digests of mammalian cell lysate, an increase of over 40% for detected peptides and over 20% for detected proteins. Additionally, we tested the instrument on peptide phosphorylation enriched samples, for which an improvement of up to 60% class I sites was observed.


Milk for small infants.
This study investigated weight patterns of infants born SGA, in relation to two different feeding regimens during hospital stay. We compared 21 SGA infants prescribed 200 mL/kg milk on day 2, with 21 infants, prescribed 170 mL/kg on day 9. The infants fed according to the proactive nutrition policy tolerated large volumes of milk and showed lower weight loss. A proactive nutrition policy demonstrably reduces weight loss in SGA infants.


A multi-site comparison of environmental characteristics to support workplace walking.
This study assessed the environmental characteristics of ten universities, comparing the extent to which physical infra-structures are able to support a route-based walking intervention. Following protocol standardization between and within sites, major pedestrian routes at main suburban campuses in seven countries (Australia, Canada, England, Northern Ireland, Scotland, Spain and the United States) were audited by researchers using an established inventory (March-June 2008). The inventory assessed key characteristics (e.g. size and employee number) and nine specific items (pedestrian facilities, vehicle conflicts, crossings, route-maintenance, walkway width, roadway buffer, universal accessibility, aesthetics and cover), scored on a five-point scale (1=very poor; 5=excellent). Item scores for each route, were combined and weighted, to provide indicators of low (score of 20-39), fair (score of 40-69), or good (score of 70-100) physical infra-structure support. Sites varied in area (range of 7-1000 acres) and employee numbers (range of 700-7500 employees). Audits reported good support for route-based walking at seven sites (overall route score range=72.5+/-13.9-82.2+/-17.4), fair support at two sites (overall route score of 69.1+/-11.7 and 61.7+/-14.6), and low support at one site (overall route score of 22.1+/-7.3). Study methods highlight a valuable audit process, while findings identify the need to improve aspects of physical infra-structure at sites where the built environment may be less conducive for route-based walking.


[Temperament traits associated with bipolar affective disorder: an integrative literature review].
Studies have suggested an association between temperament characteristics and adjustment and psychiatric disorders, describing them as different manifestations of vulnerability to psychopathology. The objective of this study was to conduct an integrative review of the literature on temperament traits typical of bipolar patients in relation to the general population. A systematic search was conducted on the MEDLINE, PsycINFO and LILACS databases, using the headings bipolar disorder, temperament and/or personality, between January 2000 and December 2010. The search was performed in January 2011. A total of 199 articles were identified for potential inclusion in the review. After application of the exclusion criteria, a total of 15 articles were selected and their full texts analyzed. Review of the selected studies revealed heterogeneity in terms of sample profile and specific temperament traits assessed with the appropriate instruments. Temperament traits in bipolar patients are identified based on different theoretical models. The results of five studies consistently showed that neuroticism is a distinct personality trait in the temperament profile of bipolar patients. Future reviews should use more specific keywords and limit the search to studies with a longitudinal design.


Preoperative Distress Predicts Persistent Pain After Breast Cancer Treatment: A Prospective Cohort Study.
Persistent pain after breast cancer treatment (PPBCT) affects 25% to 60% of breast cancer survivors and is recognized as a clinical problem, with 10% to 15% reporting moderate to severe pain several years after treatment. Psychological comorbidity is known to influence pain perception, and evidence links signs of depression and anxiety with development of PPBCT. The purpose of this study was to assess preoperative distress as a predictive factor for development of PPBCT. Between October 2008 and October 2009, 426 women diagnosed with primary breast cancer, undergoing surgery at the Department of Breast Surgery, Rigshospitalet, Denmark, were invited to participate in the study. Patients filled out a questionnaire preoperatively, and 4 and 8 months after surgery. Preoperative distress was measured with the Distress Thermometer (DT; 11-point scale, 0-10). We examined the association between severe preoperative distress (using DT ≥7) and moderate to severe PPBCT 8 months after diagnosis using a logistic regression model. A total of 357 patients participated in this study and 291 (82%) returned all follow-up questionnaires. Preoperative distress was significantly associated with moderate to severe PPBCT at 8 months, with an adjusted odds ratio (OR) of 2.05 (95% CI, 1.18-3.59; P=.01), and at 4 months, with an OR of 2.23 (95% CI, 1.23-4.05; P=.01). Preoperative distress was associated with PPCBT, suggesting distress as an independent risk factor for PPBCT. Preoperative identification of patients at risk for PPBCT allows for further research in psychological and pharmacological treatment of this condition.


Roles of the fructans from leaf sheaths and from the elongating leaf bases in the regrowth following defoliation of Lolium perenne L.
The study of carbohydrate metabolism in perennial ryegrass (Lolium perenne L. cv. Bravo) during the first 48 h of regrowth showed that fructans from elongating leaf bases were hydrolysed first whereas fructans in mature leaf sheaths were degraded only after a lag of 1.5 h. In elongating leaf bases, the decline in fructan content occurred not only in the differentiation zone (30-60 mm from the leaf base), but also in the growth zone. Unlike other soluble carbohydrates, the net deposition rate of fructose remained positive and even rose during the first day following defoliation. The activity of fructan exohydrolase (FEH; EC 220.127.116.11) was maximal in the differentiation zone before defoliation and increased in all segments, but peaked in the growth zone after defoliation. These data strongly indicate that fructans stored in the leaf growth zone were hydrolysed and recycled in that zone to sustain the refoliation immediately after defoliation. Despite the depletion of carbohydrates, leaves of defoliated plants elongated at a significantly higher rate than those of undefoliated plants, during the first 10 h of regrowth. This can be partly attributed to the transient increase in water and nitrate deposition rate. The results are discussed in relation to defoliation tolerance.


2019 HRS/EHRA/APHRS/LAHRS focused update to 2015 expert consensus statement on optimal implantable cardioverter-defibrillator programming and testing.
The 2015 HRS/EHRA/APHRS/SOLAECE Expert Consensus Statement on Optimal Implantable Cardioverter-Defibrillator Programming and Testing provided guidance on bradycardia programming, tachycardia detection, tachycardia therapy, and defibrillation testing for implantable cardioverter-defibrillator (ICD) patient treatment. The 32 recommendations represented the consensus opinion of the writing group, graded by Class of Recommendation and Level of Evidence. In addition, Appendix B provided manufacturer-specific translations of these recommendations into clinical practice consistent with the recommendations within the parent document. In some instances, programming guided by quality evidence gained from studies performed in devices from some manufacturers was translated such that this programming was approximated in another manufacturer's ICD programming settings. The authors found that the data, although not formally tested, were strong, consistent, and generalizable beyond the specific manufacturer and model of ICD. As expected, because these recommendations represented strategic choices to balance risks, there have been reports in which adverse outcomes were documented with ICDs programmed to Appendix B recommendations. The recommendations have been reviewed and updated to minimize such adverse events. Notably, patients who do not receive unnecessary ICD therapy are not aware of being spared potential harm, whereas patients in whom their ICD failed to treat life-threatening arrhythmias have their event recorded in detail. The revised recommendations employ the principle that the randomized trials and large registry data should guide programming more than anecdotal evidence. These recommendations should not replace the opinion of the treating physician who has considered the patient's clinical status and desired outcome via a shared clinical decision-making process.


Atmospheric plasma inactivation of foodborne pathogens on fresh produce surfaces.
A study was conducted to determine the effect of one atmosphere uniform glow discharge plasma (OAUGDP) on inactivation of Escherichia coli O157:H7, Salmonella, and Listeria monocytogenes on apples, cantaloupe, and lettuce, respectively. A five-strain mixture of cultured test organisms was washed, suspended in phosphate buffer, and spot inoculated onto produce (7 log CFU per sample). Samples were exposed inside a chamber affixed to the OAUGDP blower unit operated at a power of 9 kV and frequency of 6 kHz. This configuration allows the sample to be placed outside of the plasma generation unit while allowing airflow to carry the antimicrobial active species, including ozone and nitric oxide, onto the food sample. Cantaloupe and lettuce samples were exposed for 1, 3, and 5 min, while apple samples were exposed for 30 s, 1 min, and 2 min. After exposure, samples were pummeled in 0.1% peptone water-2% Tween 80, diluted, and plated in duplicate onto selective media and tryptic soy agar and incubated as follows: E. coli O157:H7 (modified eosin methylene blue) and Salmonella (xylose lysine tergitol-4) for 48 h at 37 degrees C, and L. monocytogenes (modified Oxford medium) at 48 h for 32 degrees C. E. coli O157:H7 populations were reduced by >1 log after 30-s and 1-min exposures and >2 log after a 2-min exposure. Salmonella populations were reduced by >2 log after 1 min. Three- and 5-min exposure times resulted in >3-log reduction. L. monocytogenes populations were reduced by 1 log after 1 min of exposure. Three- and 5-min exposure times resulted in >3- and >5-log reductions, respectively. This process has the capability of serving as a novel, nonthermal processing technology to be used for reducing microbial populations on produce surfaces.


MMP-1 and Pro-MMP-10 as potential urinary pharmacodynamic biomarkers of FGFR3-targeted therapy in patients with bladder cancer.
The aim of this study was to identify noninvasive pharmacodynamic biomarkers of FGFR3-targeted therapies in bladder cancer to facilitate the clinical development of experimental agent targeting FGFR3. Potential soluble pharmacodynamic biomarkers of FGFR3 were identified using a combination of transcriptional profiling and biochemical analyses in preclinical models. Two matrix metalloproteinases (MMP), MMP-1 and MMP-10, were selected for further studies in human bladder cancer xenograft models treated with a specific anti-FGFR3 monoclonal antibody, R3Mab. Serum and urinary levels of MMP-1 and MMP-10 were determined in healthy donors and patients with bladder cancer. The modulation of MMP-1 and MMP-10 by R3Mab in patients with bladder cancer was further evaluated in a phase I dose-escalation study. MMP-1 and MMP-10 mRNA and protein were downmodulated by FGFR3 shRNA and R3Mab in bladder cancer cell lines. FGFR3 signaling promoted the expression and secretion of MMP-1 and pro-MMP-10 in a MEK-dependent fashion. In bladder cancer xenograft models, R3Mab substantially blocked tumor progression and reduced the protein levels of human MMP-1 and pro-MMP-10 in tumor tissues as well as in mouse serum. Furthermore, both MMP-1 and pro-MMP-10 were elevated in the urine of patients with advanced bladder cancer. In a phase I dose-escalation trial, R3Mab administration resulted in an acute reduction of urinary MMP-1 and pro-MMP-10 levels in patients with bladder cancer. These findings reveal a critical role of FGFR3 in regulating MMP-1 and pro-MMP-10 expression and secretion, and identify urinary MMP-1 and pro-MMP-10 as potential pharmacodynamic biomarkers for R3Mab in patients with bladder cancer.


Elevated surface temperature depresses survival of banner-tailed kangaroo rats: will climate change cook a desert icon?
Modest increases in global temperature have been implicated in causing population extirpations and range shifts in taxa inhabiting colder environs and in ectotherms whose thermoregulation is more closely tied to environmental conditions. Many arid-adapted endotherms already experience conditions at their physiological limits, so it is conceivable that they could be similarly affected by warming temperatures. We explored how climatic variables might influence the apparent survival of the banner-tailed kangaroo rat (Dipodomys spectabilis), a rodent endemic to the Chihuahuan Desert of North America and renowned for its behavioral and physiological adaptations to arid environments. Relative variable weight, strength of variable relationships, and other criteria indicated that summer, diurnal land surface temperature (SD_LST) was the primary environmental driver of apparent survival in these arid-adapted rodents. Higher temperatures had a negative effect on apparent survival, which ranged from 0.15 (SE = 0.04) for subadults to 0.50 (SE = 0.07) for adults. Elevated SD_LST may negatively influence survival through multiple pathways, including increased water loss and energy expenditure that could lead to chronic stress and/or hyperthermia that could cause direct mortality. Land surface temperatures are predicted to increase by as much 6.5°C by 2099, reducing apparent survival of adults to ~0.15 in some regions of the species' range, possibly causing a shift in their distribution. The relationship between SD_LST and survival suggests a mechanism whereby physiological tolerances are exceeded resulting in a reduction to individual fitness that may ultimately cause a shift in the species' range over time.


Reorganization of myofilament proteins and decreased cGMP-dependent protein kinase in the human uterus during pregnancy.
Excessive or premature contractions of uterine smooth muscle may contribute to preterm labor. Contractile stimuli induce myosin and actin filament interactions through calcium-dependent myosin phosphorylation. The mechanisms that maintain myometrial quiescence until term are not well established, but may include control of calcium levels by nitric oxide and cGMP signaling and thin filament (caldesmon and calponin) regulation. Previously, we reported that myometrial tissues from pregnant rats are not responsive to cGMP due to decreases in cGMP-dependent protein kinase. Considering the well documented differences in the endocrinology of parturition among species, this study was conducted to test the hypothesis that the levels and subcellular distribution of caldesmon, calponin, and cGMP-dependent protein kinase are regulated with the hormonal milieu of human pregnancy. Whereas cGMP-dependent protein kinase was significantly reduced in the human uterus during pregnancy, caldesmon expression was significantly increased, and both caldesmon and calponin were redistributed to a readily extractable subcellular pool. These data suggest that cGMP-dependent protein kinase does not mediate gestational quiescence. Redistribution of thin filament-associated proteins, however, may alter uterine smooth muscle tone or the cytoskeletal framework of myocytes to maintain gestation despite the substantial distention that accompanies all intrauterine pregnancies.


Potassium-modulated secretion of immunoreactive melanocyte-stimulating hormone and endorphin from mouse neuro-intermediate lobes: evidence for stimulus-secretion uncoupling and rate sensitivity.
A multi-chamber perifusion system, capable of detecting transient secretory events, was used to define the roles of stepwise changes and gradients of K+ concentration in modulation of alpha-MSH and endorphin secretion. Fifteen dispersed mouse neuro-intermediate lobes per chamber were perifused with Dulbecco's Modified Eagle Medium at 0.5 ml/min. One-min fractions were collected. Ten min of 67 mM K+ elicited an immediate, very brief 4-fold increase in secretion of both hormones. Surprisingly, the return to normal K+ elicited a similar increase in secretion. Ten min K+-free medium produced an immediate decrease in secretion. Exposure to a 10-min 0-67 mM K+ gradient did not produce an increase in secretion; however, the stepwise return to normal K+, identical to that in the first experiment, elicited an immediate, brief increase in secretion. 1) The rapid decline in secretory activity during 67 mM K+ cannot be explained either by "down regulation" of receptors, since this secretagogue is not receptor-mediated, or by depletion of labile hormone, since a second secretory episode occurred immediately following termination of high K+. This suggests that some other cellular mechanism "uncouples" stimulus-secretory mechanisms. 2) Although depolarization with high K+ and hyperpolarization with K+-free medium were associated with increases and decreases, respectively, in secretion, it appears that it is the rate of ion flux rather than polarization which is responsible for stimulus-secretion coupling.


MiR-27 as a prognostic marker for breast cancer progression and patient survival.
MicroRNA-27a (miR-27a) is thought to be an onco-microRNA that promotes tumor growth and metastasis by downregulating ZBTB10. The potential predictive value of miR-27a was studied in breast cancer patients. The expression of miR-27a and ZBTB10 was examined in 102 breast cancer cases using in situ hybridization (ISH) and immunohistochemistry techniques and were evaluated semi-quantitatively by examining the staining index. The Correlation of miR-27a and ZBTB10 expression was analyed by Spearman Rank Correlation. The association of miR-27a and ZBTB10 expression with clinicopathological characteristics was analyzed using the χ(2) test, and their effects on patient survival were analyzed by a log-rank test and the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were used to evaluate the prognostic values of miR-27a and ZBTB10. miR-27a was markedly up-regulated in invasive breast cancers that expressed low levels of ZBTB10 (P<0.001). A reverse correlation between miR-27a and ZBTB10 was also observed in breast cancer tissue samples (r(s) = -0.478, P<0.001). Furthermore, the expression of miR-27a and ZBTB10 was significantly correlated with clinicopathological parameters, including tumor size, lymph node metastasis and distant metastasis (P<0.05), but not with receptor status. Patients with high miR-27a or low ZBTB10 expression tended to have significantly shorter disease-free survival times (57 months and 53 months, respectively, P <0.001) and overall survival times (58 months and 55 months, respectively, P <0.001). Univariate and multivariate analysis showed that both miR-27a and ZBTB10 were independent prognostic factors of disease-free survival in breast cancer patients (P <0.001), while only miR-27a was an independent predictor of overall survival (P <0.001). High miR-27a expression is associated with poor overall survival in patients with breast cancer, which suggests that miR-27a could be a valuable marker of breast cancer progression.


Genomic insights into the taxonomic status of the three subspecies of Bacillus subtilis.
Bacillus subtilis contains three subspecies, i.e., subspecies subtilis, spizizenii, and inaquosorum. As these subspecies are phenotypically indistinguishable, their differentiation has relied on phylogenetic analysis of multiple protein-coding gene sequences. B. subtilis subsp. inaquosorum is a recently proposed taxon that encompasses strain KCTC 13429(T) and related strains, which were previously classified as members of subspecies spizizenii. However, DNA-DNA hybridization (DDH) values among the three subspecies raised a question as to their independence. Thus, we evaluated the taxonomic status of subspecies inaquosorum using genome-based comparative analysis. In contrast to the previous experimental values of DDH, the inter-genomic relatedness inferred by average nucleotide identity (ANI) values indicated that subspecies inaquosorum and spizizenii were sufficiently different from subspecies subtilis and hence raised the possibility that the former two could be classified as separate species from B. subtilis. The genome-based tree also supported the separation of the two subspecies from B. subtilis. The exclusive presence of a subtilin synthesis system in subspecies spizizenii was a remarkable genetic characteristic that could even distinguish subspecies spizizenii from subspecies inaquosorum in addition to the low ANI values (<95%). Conclusively, the genome-based data obtained in this study demonstrated that subspecies inaquosorum and spizizenii are clearly distinguished from subspecies subtilis, and raises the possibility that these two subspecies could be classified as separate species from B. subtilis. In addition, the low ANI values between subspecies inaquosorum and spizizenii and the exclusive presence of subtilin synthesis genes in subspecies spizizenii also suggest circumscription of these two subspecies at the species level.


Cardioversion for atrial fibrillation - how to prevent thromboembolic complications?
Cardioversion is an essential component of rhythm control strategy for atrial fibrillation. The thromboembolic risk of cardioversion is well established and the mechanisms behind the phenomenon have been comprehensively described. There are several clinical aspects that are important to take into consideration when assessing the safety of cardioversion. Before proceeding to cardioversion, the probability of early treatment failure and antiarrhythmic treatment options to prevent recurrences should be carefully evaluated to avoid the risks of repeated futile cardioversions. Effective periprocedural anticoagulation is the mainstay in thromboembolic complication prevention and the first week after rhythm conversion is the most vulnerable period in this respect. Early timing of cardioversion appears to be another important measure to decrease the risk of thromboembolic complications. Transoesophageal echocardiography is useful in clinical scenarios where early cardioversion is desirable due to debilitating clinical symptoms and a short duration of arrhythmia or the adequacy of preceding anticoagulation is uncertain. However, it does not lessen the need for effective anticoagulation after cardioversion. This review summarizes the recent scientific discoveries to improve the safety of cardioversion for atrial fibrillation. Key messages Cardioversion for atrial fibrillation entails a significant risk of thromboembolic complications, especially during the first week after the procedure. The intensity of periprocedural anticoagulation and the timing of cardioversion appear to be significant determinants of the risk of thromboembolism. Awareness of the clinical aspects influencing cardioversion safety should be raised.


"Get the Balance Right": Pathological Significance of Autophagy Perturbation in Neuromuscular Disorders.
Recent research has revealed that autophagy, a major catabolic process in cells, is dysregulated in several neuromuscular diseases and contributes to the muscle wasting caused by non-muscle disorders (e.g. cancer cachexia) or during aging (i.e. sarcopenia). From there, the idea arose to interfere with autophagy or manipulate its regulatory signalling to help restore muscle homeostasis and attenuate disease progression. The major difficulty for the development of therapeutic strategies is to restore a balanced autophagic flux, due to the dynamic nature of autophagy. Thus, it is essential to better understand the mechanisms and identify the signalling pathways at play in the control of autophagy in skeletal muscle. A comprehensive analysis of the autophagic flux and of the causes of its dysregulation is required to assess the pathogenic role of autophagy in diseased muscle. Furthermore, it is essential that experiments distinguish between primary dysregulation of autophagy (prior to disease onset) and impairments as a consequence of the pathology. Of note, in most muscle disorders, autophagy perturbation is not caused by genetic modification of an autophagy-related protein, but rather through indirect alteration of regulatory signalling or lysosomal function. In this review, we will present the mechanisms involved in autophagy, and those ensuring its tight regulation in skeletal muscle. We will then discuss as to how autophagy dysregulation contributes to the pathogenesis of neuromuscular disorders and possible ways to interfere with this process to limit disease progression.


High mobility, printable, and solution-processed graphene electronics.
The ability to print graphene sheets onto large scale, flexible substrates holds promise for large scale, transparent electronics on flexible substrates. Solution processable graphene sheets derived from graphite can form stable dispersions in solutions and are amenable to bulk scale processing and ink jet printing. However, the electrical conductivity and carrier mobilities of this material are usually reported to be orders of magnitude poorer than that of the mechanically cleaved counterpart due to its higher density of defects, which restricts its use in electronics. Here, we show that by optimizing several key factors in processing, we are able to fabricate high mobility graphene films derived from large sized graphene oxide sheets, which paves the way for all-carbon post-CMOS electronics. All-carbon source-drain channel electronics fabricated from such films exhibit significantly improved transport characteristics, with carrier mobilities of 365 cm(2)/(V.s) for hole and 281 cm(2)/(V.s) for electron, measured in air at room temperature. In particular, intrinsic mobility as high as 5000 cm(2)/(V.s) can be obtained from such solution-processed graphene films when ionic screening is applied to nullify the Coulombic scattering by charged impurities.


Azithromycin versus placebo for the treatment of HIV-associated chronic lung disease in children and adolescents (BREATHE trial): study protocol for a randomised controlled trial.
Human immunodeficiency virus (HIV)-related chronic lung disease (CLD) among children is associated with substantial morbidity, despite antiretroviral therapy. This may be a consequence of repeated respiratory tract infections and/or dysregulated immune activation that accompanies HIV infection. Macrolides have anti-inflammatory and antimicrobial properties, and we hypothesised that azithromycin would reduce decline in lung function and morbidity through preventing respiratory tract infections and controlling systemic inflammation. We are conducting a multicentre (Malawi and Zimbabwe), double-blind, randomised controlled trial of a 12-month course of weekly azithromycin versus placebo. The primary outcome is the mean change in forced expiratory volume in 1 second (FEV1) z-score at 12 months. Participants are followed up to 18 months to explore the durability of effect. Secondary outcomes are FEV1 z-score at 18 months, time to death, time to first acute respiratory exacerbation, number of exacerbations, number of hospitalisations, weight for age z-score at 12 and 18 months, number of adverse events, number of malaria episodes, number of bloodstream Salmonella typhi infections and number of gastroenteritis episodes. Participants will be followed up 3-monthly, and lung function will be assessed every 6 months. Laboratory substudies will be done to investigate the impact of azithromycin on systemic inflammation and on development of antimicrobial resistance as well as impact on the nasopharyngeal, lung and gut microbiome. The results of this trial will be of clinical relevance because there are no established guidelines on the treatment and management of HIV-associated CLD in children in sub-Saharan Africa, where 80% of the world's HIV-infected children live and where HIV-associated CLD is highly prevalent. ClinicalTrials.gov, NCT02426112 . Registered on 21 April 2015.


Effect of Mobile Phone Radiation on Cardiovascular Development of Chick Embryo.
The biological effects on cardiovascular development of chicken embryos were examined after radiation exposure using mobile phone (900 MHz; specific absorption rate˜1.07 W/kg) intermittently 3 h per day during incubation. Samples were selected by morphological and histological methods. The results showed the rate of embryonic mortality and cardiac deformity increased significantly in exposed group (P < 0.05). No any histological pathological changes were observed on Day 5-7 (D5-D7) of incubation. A higher distribution of lipid droplets was unexpectedly present in myocardial tissue from the exposure groups on D10-D13. Soon afterwards, myofilament disruption, atrioventricular valve focal necrosis, mitochondria vacuolization and atrial natriuretic peptide (ANP) decrease appeared on D15-D21 of incubation. Comet assay data showed the haemocyte mean tail in the exposed group was significantly larger than that of the control (P < 0.01). The arterial vascular wall of exposed group was thicker (P < 0.05) than that of the control on D13, which was reversed to normal in later stages. Our findings suggest that long-term exposure of MPR may induce myocardium pathological changes, DNA damage and increased mortality; however, there was little effect on vascular development.


Prospective assessment of complications associated with ultrasound activated resorbable pin osteosynthesis in pediatric craniofacial surgery: preliminary results.
Ultrasound activated resorbable pin osteosynthesis (UARPO) has recently shown favourable results in operations on children suffering for craniosynostosis. However, data on complications coming with this new technique in children suffering from craniosynostoses are scarce and have only been assessed retrospectively so far. It has been the aim of the present study to prospectively follow up children undergoing craniosynostosis surgery with a focus on complications related to UARPO materials. Ten pediatric patients (3 female/7 male) were operated due to craniosynostosis at an average age of 9.1±3.8 months using UARPO (SonicWeld/Resorb-X, KLS Martin, Tuttlingen, Germany). Clinical followup evaluations were carried out 1, 3, 6, 9, 12 and 18 months after surgery according to signs of local infection, stability of the remodeled cranial vault and the palpability of the osteosynthesis material. If secondary surgery was necessary, the indication was documented and evaluated by histological and wound smear examinations. No intra-operative or postoperative complications during the inpatient period occurred. 3 patients needed secondary operation due to a localized chronic swelling at the former incision site which developed 3, 9 and 12 months after the operation. Histological examinations yielded a giant cell formation surrounding the resorbable materials in all cases. Additionally, the wound smear showed a bacterial infection in one site. The current prospective study is the first in the field. It reveals a high percentage of delayed foreign body reactions with UARPO, bearing the need of secondary surgery. It seems that this high complication rate found in the present prospective study may weigh out the advantages of UARPO.


Personalizing Psychological Treatment Along the IBD Journey: From Diagnosis to Surgery.
Personalized medicine is becoming a widespread effort to provide the right treatment to the right patient at the right time. However, it lacks of consideration for nonmedical factors, such as patient preferences and psychosocial factors, which should not be avoided. The present study summarizes the psychosocial difficulties experienced by patients with inflammatory bowel disease (IBD) during different phases of the disease in order to identify methods to assess psychosocial risk factors and personalize treatment strategies. To reach this goal, the quantitative literature is matched with the patients' perspective, offering a broad overview of psychosocial risk factors that IBD patients experience. Quantitative results offer strong evidences for specific psychosocial risk factors in IBD and for weak results of psychosocial interventions, but show a lack of individually tailored researches, instruments and interventions, increasing the distance between the research findings and clinical practice. At the same time, qualitative findings show important, though veiled information uncovered by the quantitative research (e.g., identity recovery, fight for control, sexual concerns), which may be used as a starting point for further explorations. The present study suggests a need to adopt individualized therapeutic approach and deliver psychological therapies while taking into account patients' experiences and preferences.


Effects of intranasal oxytocin on emotional face processing in women.
The neuropeptide oxytocin (OXT) has previously been found to reduce amygdala reactivity to social and emotional stimuli in healthy men. The present study aimed to investigate the effect of intranasally administered OXT on brain activity in response to social emotional stimuli of varying valence in women. In a functional magnetic-resonance imaging study, sixteen women were presented with fearful, angry, happy and neutral facial expressions after a single dose of 24IU OXT or a placebo administration in a within-subject design. Group analysis revealed that the blood-oxygen-level-dependent (BOLD) signal was enhanced in the left amygdala, the fusiform gyrus and the superior temporal gyrus in response to fearful faces and in the inferior frontal gyrus in response to angry and happy faces following OXT treatment. This effect was independent of fixation pattern to specific sections of the facial stimuli as revealed by eye tracking and independent of basal plasma levels of OXT, estradiol, and progesterone. The results are at odds with the previously reported effects found in men. Future studies should include both sexes to determine a possible sexual dimorphism in the neural effects of OXT, considering gonadal steroids and OXT receptor affinity.


When fever is not malaria in Latin America: a systematic review.
In malaria-endemic countries, febrile episodes caused by diseases other than malaria are a growing concern. However, limited knowledge of the prevalent etiologic agents and their geographic distributions restrict the ability of health services to address non-malarial morbidity and mortality through effective case management. Here, we review the etiology of fever in Latin America (LA) between 1980 and 2015 and map significant pathogens commonly implicated in febrile infectious diseases. A literature search was conducted, without language restrictions, in three distinct databases in order to identify fever etiology studies that report laboratory-confirmed fever-causing pathogens that were isolated from usually sterile body sites. Data analyses and mapping was conducted with Tableau Desktop (version 2018.2.3). Inclusion criteria were met by 625 publications corresponding to data relative to 34 countries. Studies using serology (n = 339) predominated for viral infections, culture (n = 131) for bacteria, and microscopy (n = 62) for fungi and parasites. The pathogen groups most frequently reported were viral infections (n = 277), bacterial infections (n = 265), parasitic infections (n = 59), fungal infections (n = 47), and more than one pathogen group (n = 24). The most frequently reported virus was dengue virus (n = 171), followed by other arboviruses (n = 55), and hantavirus (n = 18). For bacteria, Staphylococcus spp. (n = 82), Rickettsia spp. (n = 70), and Leptospira spp. (n = 55) were frequently reported. Areas with biggest gaps on etiology of fever were apparent. This review provides a landscape of pathogens causing febrile illness other than malaria in LA for over 30 years. Our findings highlight the need to standardize protocols and report guidelines for fever etiology studies for better comparability of results and improved interpretation. Lastly, we should improve existing national laboratory surveillance systems, especially from low- to middle-income countries, to inform global fever policy priorities and timely identify emerging infections threats. PROSPERO systematic review registration number: CRD42016049281.


Long-term exposure to ethanol increases the number and function of muscarinic M1 receptors in human neuroblastoma cells.
The effect of long-term ethanol exposure on muscarinic receptors was investigated in human neuroblastoma SH-SY5Y cells. Exposure to 100 mM ethanol for 4 days enhanced both peak and steady-state levels of carbachol-stimulated inositol 1,4,5-bisphosphate increase. An ethanol concentration of 50 mM was sufficient for an enhancement of this event. The carbachol-stimulated decrease in [3H]inositol-labeled [3H]phosphatidylnositol 4,5-bisphosphate and increase [3H]inositol trisphosphate and [3H]inositol bisphosphate were also potentiated in ethanol-treated cells, which demonstrated that the receptor-stimulated activation of phospholipase C is augmented. Experiments with pirenzepine showed that carbachol-stimulated inositol 1,4,5-trisphosphate increase is mediated via M1 receptors both in ethanol-treated and control cells. Ethanol exposure for 2 or 4 days also caused an increase in [3H]N-methylscopolamine and [3H]quinuclidinyl benzilate binding sites and elevation of [3H]pirenzepine binding, which indicated that the number of muscarinic M1 receptors is increased in ethanol-treated SH-SY5Y cells. These results demonstrate that long-term exposure to ethanol potentiates muscarinic M1 receptor-stimulated activation of phospholipase C in SH-SY5Y cells. This is likely to be explained by an increased number of muscarinic M1 receptors.


Investigation of the role of the BAM complex and SurA chaperone in outer-membrane protein biogenesis and type III secretion system expression in Salmonella.
In Escherichia coli, the assembly of outer-membrane proteins (OMP) requires the BAM complex and periplasmic chaperones, such as SurA or DegP. Previous work has suggested a potential link between OMP assembly and expression of the genes encoding type-III secretion systems. In order to test this hypothesis, we studied the role of the different lipoproteins of the BAM complex (i.e. BamB, BamC, BamD and BamE), and the periplasmic chaperones SurA and DegP, in these two phenotypes in Salmonella. Analysis of the corresponding deletion mutants showed that, as previously described with the DeltabamB mutant, BamD, SurA and, to a lesser extent, BamE play a role in outer-membrane biogenesis in Salmonella Enteritidis, while the membrane was not notably disturbed in DeltabamC and DeltadegP mutants. Interestingly, we found that BamD is not essential in Salmonella, unlike its homologues in Escherichia coli and Neisseria gonorrhoeae. In contrast, BamD was the only protein required for full expression of T3SS-1 and flagella, as demonstrated by transcriptional analysis of the genes involved in the biosynthesis of these T3SSs. In line with this finding, bamD mutants showed a reduced secretion of effector proteins by these T3SSs, and a reduced ability to invade HT-29 cells. As DeltasurA and DeltabamE mutants had lower levels of OMPs in their outer membrane, but showed no alteration in T3SS-1 and flagella expression, these results demonstrate the absence of a systematic link between an OMP assembly defect and the downregulation of T3SSs in Salmonella; therefore, this link appears to be related to a more specific mechanism that involves at least BamB and BamD.


GLP-1 receptor agonists show neuroprotective effects in animal models of diabetes.
Enzyme-resistant receptor agonists of the incretin hormone glucagon-like peptide-1 (GLP-1) have shown positive therapeutic effects in people with type 2 diabetes mellitus (T2DM). T2DM has detrimental effects on brain function and impairment of cognition and memory formation has been described. One of the underlying mechanisms is most likely insulin de-sensitization in the brain, as insulin improves cognitive impairments and enhances learning. Treatment with GLP-1 receptor agonists improves memory formation and impairment of synaptic plasticity observed in animal models of diabetes-obesity. Furthermore, it has been shown that diabetes impairs growth factor signalling in the brain and reduces energy utilization in the cortex. Inflammation and apoptotic signalling was also increased. Treatment with GLP-1 receptor agonists improved neuronal growth and repair and reduced inflammation and apoptosis as well as oxidative stress. In comparison with the diabetes drug metformin, GLP-1 receptor agonists were able to improve glycemic control and reverse brain impairments, whereas metformin only normalized blood glucose levels. Clinical studies in non-diabetic patients with neurodegenerative disorders showed neuroprotective effects following administration with GLP-1 receptor agonists, demonstrating that neuroprotective effects are independent of blood glucose levels.


Construct-level predictive validity of educational attainment and intellectual aptitude tests in medical student selection: meta-regression of six UK longitudinal studies.
Measures used for medical student selection should predict future performance during training. A problem for any selection study is that predictor-outcome correlations are known only in those who have been selected, whereas selectors need to know how measures would predict in the entire pool of applicants. That problem of interpretation can be solved by calculating construct-level predictive validity, an estimate of true predictor-outcome correlation across the range of applicant abilities. Construct-level predictive validities were calculated in six cohort studies of medical student selection and training (student entry, 1972 to 2009) for a range of predictors, including A-levels, General Certificates of Secondary Education (GCSEs)/O-levels, and aptitude tests (AH5 and UK Clinical Aptitude Test (UKCAT)). Outcomes included undergraduate basic medical science and finals assessments, as well as postgraduate measures of Membership of the Royal Colleges of Physicians of the United Kingdom (MRCP(UK)) performance and entry in the Specialist Register. Construct-level predictive validity was calculated with the method of Hunter, Schmidt and Le (2006), adapted to correct for right-censorship of examination results due to grade inflation. Meta-regression analyzed 57 separate predictor-outcome correlations (POCs) and construct-level predictive validities (CLPVs). Mean CLPVs are substantially higher (.450) than mean POCs (.171). Mean CLPVs for first-year examinations, were high for A-levels (.809; CI: .501 to .935), and lower for GCSEs/O-levels (.332; CI: .024 to .583) and UKCAT (mean = .245; CI: .207 to .276). A-levels had higher CLPVs for all undergraduate and postgraduate assessments than did GCSEs/O-levels and intellectual aptitude tests. CLPVs of educational attainment measures decline somewhat during training, but continue to predict postgraduate performance. Intellectual aptitude tests have lower CLPVs than A-levels or GCSEs/O-levels. Educational attainment has strong CLPVs for undergraduate and postgraduate performance, accounting for perhaps 65% of true variance in first year performance. Such CLPVs justify the use of educational attainment measure in selection, but also raise a key theoretical question concerning the remaining 35% of variance (and measurement error, range restriction and right-censorship have been taken into account). Just as in astrophysics, 'dark matter' and 'dark energy' are posited to balance various theoretical equations, so medical student selection must also have its 'dark variance', whose nature is not yet properly characterized, but explains a third of the variation in performance during training. Some variance probably relates to factors which are unpredictable at selection, such as illness or other life events, but some is probably also associated with factors such as personality, motivation or study skills.


Decellularized Adipose Tissue Hydrogel Promotes Bone Regeneration in Critical-Sized Mouse Femoral Defect Model.
Critical-sized bone defects fail to heal and often cause non-union. Standard treatments employ autologous bone grafting, which can cause donor tissue loss/pain. Although several scaffold types can enhance bone regeneration, multiple factors limit their level of success. To address this issue, this study evaluated a novel decellularized human adipose tissue (DAT) hydrogel as an alternative. In this study, DAT hydrogel alone, or in combination with adipose-derived stromal/stem cells (ASC), osteo-induced ASCs (OIASC), and hydroxyapatite were tested for their ability to mediate repair of a critical-sized (3 mm) femoral defect created in C57BL/6 mice. Micro-computed tomography results showed that all DAT hydrogel treated groups significantly enhanced bone regeneration, with OIASC + hydroxyapatite treated group displaying the most robust bone regeneration. Histological analyses revealed that all treatments resulted in significantly higher tissue areas with the relative mineralized tissue area significantly increased at 12 weeks; however, cartilaginous content was lowest among treatment groups with OIASC. Immunohistochemical analyses showed that DAT hydrogel enhanced collagen I and osteopontin expression, while the addition of OIASCs to the hydrogel reduced collagen II levels. Thus, DAT hydrogel promotes bone regeneration in a critical-sized femoral defect model that is further enhanced in the presence of OIASCs and hydroxyapatite.


Fenhexamid Resistance in Botrytis cinerea from Strawberry Fields in the Carolinas Is Associated with Four Target Gene Mutations.
Botrytis cinerea, the causal agent of gray mold disease, is one of the most important pathogens of strawberry. Its control in commercial strawberry fields is largely dependent on the application of fungicides during bloom and fruit maturation. The hydroxyanilide fenhexamid is one of the most frequently used fungicides in the southeast of the United States for gray mold control. It inhibits the 3-ketoreductase (Erg27) of the ergosterol biosynthesis pathway and, due to this site-specific mode of action, is at risk for resistance development. Single-spore isolates were collected from 11 commercial strawberry fields in North and South Carolina and subjected to a conidial germination assay that distinguished sensitive from resistant phenotypes. Of the 214 isolates collected, 16.8% were resistant to fenhexamid. Resistance was found in three of four locations from North Carolina and in four of seven locations from South Carolina, indicating that resistance was widespread. Mutations in Erg27 (T63I, F412S, F412C, and F412I) were associated with resistance, with F412S the predominant and most widespread mutation. In this study, mutations T63I and F412C in field isolates of B. cinerea are described for the first time. Detached fruit studies showed that field rates of Elevate 50 WDG (fenhexamid) controlled sensitive but not resistant isolates carrying any of the four mutations. Resistant isolates produced the same lesion size and number of sporulating lesions on fruit sprayed with Elevate 50 WDG as on untreated controls, showing the fungicide's loss of efficacy against those isolates. A rapid polymerase chain reaction method was developed to quickly and reliably distinguish isolates sensitive or resistant to fenhexamid in the Carolinas and to determine the mutation associated with resistance. The presence of fenhexamid-resistant strains in B. cinerea from strawberry fields in the Carolinas must be considered in future resistance management practices for sustained gray mold control.


The behaviour of 134Cs, 60Co, and 85Sr radionuclides in marine environmental sediment.
This work describes experimental investigations and modelling studies on the sorption of radionuclides 134Cs, 60Co, and 85Sr by certain marine sediments within Egypt. The chemical composition of the marine sediments was determined. The soluble salts were measured for the sediments and the concentrations of the released cations, Al3+, Fe3+, and Si4+, were measured for the sediment materials in 0.1 M NaClO4 aqueous solution at different hydrogen ion concentrations. The two main factors that control the uptake of the radionuclides onto the sediment are the pH and the exchangeable capacities of the sediment materials. Surface complex model was used to estimate the surface charge densities and the electric surface potential of the marine sediment materials. These two parameters were calculated at the surface capacity sites of the sediment materials. The desorption of the adsorbed cations was determined by means of selective consecutive extraction tests using different chemical reagents including (1) 1 M MgCl2 (pH 7), (2) 1 M ammonium oxalate (pH 3-5), (3) 0.04 M NH2OH,HCl in 25% acetic acid (pH 3-4), (4) H2O2 in 5% HNO3(pH 2-3), and (5) digestion with nitric acid followed by hydrofluoric and perchloric acids (pH 2).


Dynamic changes in transcripts during regeneration of the secondary vascular system in Populus tomentosa Carr. revealed by cDNA microarrays.
Wood is the end product of secondary vascular system development, which begins from the cambium. The wood formation process includes four major stages: cell expansion, secondary wall biosynthesis, lignification, and programmed cell death. Transcriptional profiling is a rapid way to screen for genes involved in these stages and their transitions, providing the basis for understanding the molecular mechanisms that control this process. In this study, cDNA microarrays were prepared from a subtracted cDNA library (cambium zone versus leaf) of Chinese white poplar (Populus tomentosa Carr.) and employed to analyze the transcriptional profiles during the regeneration of the secondary vascular system, a platform established in our previous study. Two hundred and seven genes showed transcript-level differences at the different regeneration stages. Dramatic transcriptional changes were observed at cambium initiation, cambium formation and differentiation, and xylem development, suggesting that these up- or downregulated genes play important roles in these stage transitions. Transcription factors such as AUX/IAA and PINHEAD, which were previously shown to be involved in meristem and vascular tissue differentiation, were strongly transcribed at the stages when cambial cells were initiated and underwent differentiation, whereas genes encoding MYB proteins and several small heat shock proteins were strongly transcribed at the stage when xylem development begins. Employing this method, we observed dynamic changes in gene transcript levels at the key stages, including cambium initiation, cambium formation and differentiation, and xylem development, suggesting that these up- or downregulated genes are strongly involved in these stage transitions. Further studies of these genes could help elucidate their roles in wood formation.


Expression and significance of FXYD-3 protein in gastric adenocarcinoma.
FXYD-3, also known as Mat-8, is a member of the FXYD protein family. It was reported that this protein can associate with and modify the transport properties of Na, K-ATPase, and may play an important role in a variety of physiological and pathological states. This protein is up-regulated in certain types of cancers (such as breast, prostate and pancreatic cancer), but down-regulated in other types of cancers (such as colon and kidney cancer). No study has been performed in gastric cancer; therefore, the aim of this project was to investigate FXYD-3 expression and its clinicopathological significance in gastric adenocarcinoma. FXYD-3 protein was examined by immunohistochemistry in normal gastric mucous (n= 29) and gastric adenocarcinoma (n=51), obtained from surgical resection of gastric cancer patients. FXYD-3 protein was present in the cytoplasm of normal gastric epithelial cells or gastric cancer cells. The rate of FXYD-3 strong expression was significantly higher in cancer (51% of 51) than in normal mucosa (10% of 29, X<formula>;{2}</formula>=13.210, p < 0.0001). FXYD-3 expressed strongly in ulcerative/infiltrating types of cancers compared to polypoid/fungating ones (X<formula>;{2}</formula>=5.765, p=0.016). However, FXYD-3 expression was not correlated with patient's gender, age, tumor size, lymph node status and histological grade (p > 0.05). Conclosion: Up-regulated expression of FXYD-3 protein may be involved in tumourgenesis and invasion of gastric adenocarcinoma.


Crystal structure of chlorido-(η(2)-phenyl iso-thio-cyanate-κ(2) C,S)-mer-tris-(tri-methyl-phosphane-κP)iridium(I).
The molecule of the title compound, [IrCl(C7H5NS)(C3H9P)3], is a distorted octa-hedral iridium complex with three PMe3 ligands arranged in a meridional geometry, a chloride ion cis to all three PMe3 groups and the phenyl iso-thio-cyanate ligand bonded in an η(2)-fashion through the C and S atoms. The C atom is trans to the chloride ion and the S atom is responsible for a significant deviation from an ideal octa-hedral geometry. The geometric parameters for the metal-complexing phenyl isothiocyanate group are compared with other metal-complexed phenyl iso-thio-cyanates, as well as with examples of uncomplexed aryl iso-thio-cyanates.


Topsoil drying combined with increased sulfur supply leads to enhanced aliphatic glucosinolates in Brassica juncea leaves and roots.
The decrease of water availability is leading to an urgent demand to reduce the plants' water supply. This study evaluates the effect of topsoil drying, combined with varying sulfur (S) supply on glucosinolates in Brassica juncea in order to reveal whether a partial root drying may already lead to a drought-induced glucosinolate increase promoted by an enhanced S supply. Without decreasing biomass, topsoil drying initiated an increase in aliphatic glucosinolates in leaves and in topsoil dried roots supported by increased S supply. Simultaneously, abscisic acid was determined, particularly in dehydrated roots, associated with an increased abscisic acid concentration in leaves under topsoil drying. This indicates that the dehydrated roots were the direct interface for the plants' stress response and that the drought-induced accumulation of aliphatic glucosinolates is related to abscisic acid formation. Indole and aromatic glucosinolates decreased, suggesting that these glucosinolates are less involved in the plants' response to drought.


Comparative Effect of Lisinopril and Fosinopril in Mitigating Learning and Memory Deficit in Scopolamine-Induced Amnesic Rats.
Lisinopril and fosinopril were compared on scopolamine-induced learning and memory deficits in rats. A total of eighty-four male Wistar rats were divided into seven groups. Group I received 2% gum acacia orally for 4 weeks, group II received normal saline, and group III received scopolamine (2 mg/kg/ip) as single dose. Groups IV and V received lisinopril ( 0.225 mg/kg and 0.45 mg/kg), while Groups VI and VII received fosinopril (0.90 mg/kg and 1.80 mg/kg), respectively, orally for four weeks, followed by scopolamine (2 mg/kg/ip) given 45 minutes prior to experimental procedure. Evaluation of learning and memory was assessed by using passive avoidance, Morris water maze, and elevated plus maze tests followed by analysis of hippocampal morphology and quantification of the number of surviving neurons. Scopolamine induced marked impairment of memory in behavioral tests which correlated with morphological changes in hippocampus. Pretreatment with fosinopril 1.80 mg/kg was found to significantly ameliorate the memory deficits and hippocampal degeneration induced by scopolamine. Fosinopril exhibits antiamnesic activity, indicating its possible role in preventing memory deficits seen in dementia though the precise mechanism underlying this effect needs to be further evaluated.