Innate immune recognition of Yersinia pseudotuberculosis type III secretion.
Specialized protein translocation systems are used by many bacterial pathogens to deliver effector proteins into host cells that interfere with normal cellular functions. How the host immune system recognizes and responds to this intrusive event is not understood. To address these questions, we determined the mammalian cellular response to the virulence-associated type III secretion system (T3SS) of the human pathogen Yersinia pseudotuberculosis. We found that macrophages devoid of Toll-like receptor (TLR) signaling regulate expression of 266 genes following recognition of the Y. pseudotuberculosis T3SS. This analysis revealed two temporally distinct responses that could be separated into activation of NFkappaB- and type I IFN-regulated genes. Extracellular bacteria were capable of triggering these signaling events, as inhibition of bacterial uptake had no effect on the ensuing innate immune response. The cytosolic peptidoglycan sensors Nod1 and Nod2 and the inflammasome component caspase-1 were not involved in NFkappaB activation following recognition of the Y. pseudotuberculosis T3SS. However, caspase-1 was required for secretion of the inflammatory cytokine IL-1beta in response to T3SS-positive Y. pseudotuberculosis. In order to characterize the bacterial requirements for induction of this novel TLR-, Nod1/2-, and caspase-1-independent response, we used Y. pseudotuberculosis strains lacking specific components of the T3SS. Formation of a functional T3SS pore was required, as bacteria expressing a secretion needle, but lacking the pore-forming proteins YopB or YopD, did not trigger these signaling events. However, nonspecific membrane disruption could not recapitulate the NFkappaB signaling triggered by Y. pseudotuberculosis expressing a functional T3SS pore. Although host cell recognition of the T3SS did not require known translocated substrates, the ensuing response could be modulated by effectors such as YopJ and YopT, as YopT amplified the response, while YopJ dampened it. Collectively, these data suggest that combined recognition of the T3SS pore and YopBD-mediated delivery of immune activating ligands into the host cytosol informs the host cell of pathogenic challenge. This leads to a unique, multifactorial response distinct from the canonical immune response to a bacterium lacking a T3SS.


Trends in managed care contracting among U.S. hospitals.
This article describes the changing profile of hospitals initiating managed care contracts as of 1992. Based on statistical tests, early contractors rank higher on profitability, case mix, bed size, affiliation, and urban location. In contrast, recent and noncontractors are predominantly rural, freestanding hospitals with low case mix, low profitability, high subacute services, and government ownership. A number of lessons for the future are drawn and a stage-by-stage approach to studying managed care issues is proposed.


Low temperature-induced modifications in cell ultrastructure and localization of phenolics in winter oilseed rape (Brassica napus L. var. oleifera L.) leaves.
Acclimation of winter oilseed plants in the cold (i.e. at temperatures >0 degrees C) followed by short exposure to sub-lethal freezing temperatures resulted in pronounced ultrastructural changes of leaf epidermal and mesophyll cells. The following major changes were observed upon acclimation at 2 degrees C: increased thickness of cell walls; numerous invaginations of plasma membranes; the appearance of many large vesicles localized in the cytoplasm in close proximity to the central vacuole; the occurrence of abundant populations of microvesicles associated with the endoplasmic reticulum (ER) cisternae or located in the vicinity of dictyosomes; and the occurrence of paramural bodies and myelin-like structures. In addition, large phenolic deposits were observed in the vicinity of the plasma membrane and membrane-bound organelles such as chloroplasts, large vesicles or cytoplasm/tonoplast interfaces. Transient freezing (-5 degrees C for 18 h) of the cold-acclimated leaves led to reversible disorganization of the cytoplasm and to pronounced structural changes of the cellular organelles. Chloroplasts were swollen, with the stroma occupying one half of their volume and the thylakoid system being displaced to the other half. Large phenolic aggregates disappeared but distinct layers of phenolic deposits were associated with mitochondrial membranes and with chloroplast envelopes. In frost-thawed cells recovered at 2 degrees C for 24 h, dictyosomes and dictyosome- or ER-derived small vesicles reappeared in the ribosome-rich cytoplasm. Aberrations in the structure of chloroplasts and mitochondria were less pronounced. Few phenolic deposits were seen as small grains associated with chloroplast envelopes and vesicle membranes. These observations demonstrate that plants undergo different changes in cell ultrastructure depending on whether they are subjected to chilling or freezing temperatures. Results are discussed in relation to membrane recycling and the possible role of phenolics during the first and second stages of plant acclimation at low temperature.


Parental exposure to tebuconazole causes thyroid endocrine disruption in zebrafish and developmental toxicity in offspring.
Azole fungicides are one class of the most extensively applied current-use pesticides. Tebuconazole is a common azole fungicide that has been frequently detected in aquatic ecosystems, thus raising concerns about its ecological safety. However, adverse effects of tebuconazole remain largely unknown, especially with regard to endocrine function in aquatic organisms. In the present study, sexually immature zebrafish were exposed to different concentrations of tebuconazole (0.05, 0.20 and 0.50 mg/L) for 60 days in order to test for transgenerational toxicity on the thyroid endocrine system. Thyroid hormone homeostasis, neuronal, and cardiovascular development were investigated in the F1 generation, which were reared in tebuconazole-free water. In the F0 generation, exposure to 0.20 and 0.50 mg/L tebuconazole reduced both thyroxine (T4) and 3,5,3'-triiodothyronine (T3) levels in females, while the T3 levels were unchanged in males. Decreased heart rate was found in F1 larvae, as well as diminished T4 levels in F1 eggs/larvae. We also observed significantly increased expression of ugt1ab mRNA in two generations of zebrafish. Moreover, expression of mRNA associated with neuronal development (e.g. α1-tubulin, mbp, gap43) and cardiovascular development (e.g. cacna1ab, tnncal) were significantly downregulated in F1 larvae at 5 and 10 dpf. In addition, tebuconazole was detected in F1 eggs following parental exposure, indicating maternal transfer. This study demonstrated that tebuconazole can be transferred to offspring from exposed parents, causing thyroid endocrine disruption and developmental toxicity.


Peroxisome proliferator-activated receptor alpha deficiency impairs regulatory T cell functions: Possible application in the inhibition of melanoma tumor growth in mice.
Regulatory T (Treg) cells are important to induce and maintain immunological self-tolerance. Although the progress accomplished in understanding the functional mechanism of Treg cells, intracellular molecules that control the mechanisms of their suppressive capacity are still on investigation. The present study showed that peroxisome proliferator-activated receptor-alpha deficiency impaired the suppressive activity of Treg cells on CD4+CD25- and CD8+ T cell proliferation. In Treg cells, PPARα gene deletion also induced a decrease of migratory abilities, and downregulated the expression of chemokine receptors (CCR-4, CCR-8 and CXCR-4) and p27KIP1 mRNA. Treg cells from PPARα-/- mice also lost their anergic property. Since low Treg activity, as observed in PPARα-/- mice, is known to be associated with the inhibition of tumor growth, we inoculated these mice with B16 melanoma cells and assessed tumor proliferation. In PPARα-/- mice, cancer growth was significantly curtailed, and it was correlated with high expression of granzyme B and perforin mRNA in tumor bed. Degranulation of cytolytic molecules by CD8+ T cells, assessed by a perforin-release marker CD107a expression, was higher in PPARα-/- mice than that in wild-type mice. Tumor-infiltrating lymphocytes (TIL) in melanoma tumors in PPARα-/- mice exhibited high pro-inflammatory Th1 phenotype. Consistently, adoptive transfer into lymphopenic RAG2-/- mice of total PPARα-/-splenic T cells inhibited more the growth rate of B16 tumor than the wild type splenic T cells. Our findings suggest that PPARα deficiency, by diminishing Treg cell functions and upregulating pro-inflammatory T cell phenotype, exerts an in vivo anti-cancer properties.


Determinants of driving under the influence of alcohol or drugs among latino immigrants in miami-dade county, florida.
Little is known about the pre- and postimmigration drinking and drunk- and drugged-driving behavior of Latino immigrants. Despite showing risky drinking behaviors, many recent immigrants of low socioeconomic status (SES) do not drive while impaired by alcohol (DWI) due largely to limited access to a vehicle. This effort examines the DWI and driving while impaired by drugs (DWID) behaviors of Latino immigrants who have access to a vehicle. Data came from an ongoing longitudinal sample of Latino immigrants to Miami-Dade County, Florida. Bivariate analyses and logistic regression were applied. Preimmigration DWI and DWID was the best predictor of postimmigration DWI and DWID. Future interventions should make efforts to (a) identify immigrants who had DWI and DWID in their country of origin and (b) design and deliver specific and culturally relevant messages to persuade them not to engage in DWI and DWID after immigration.


Choosing algorithms for TB screening: a modelling study to compare yield, predictive value and diagnostic burden.
To inform the choice of an appropriate screening and diagnostic algorithm for tuberculosis (TB) screening initiatives in different epidemiological settings, we compare algorithms composed of currently available methods. Of twelve algorithms composed of screening for symptoms (prolonged cough or any TB symptom) and/or chest radiography abnormalities, and either sputum-smear microscopy (SSM) or Xpert MTB/RIF (XP) as confirmatory test we model algorithm outcomes and summarize the yield, number needed to screen (NNS) and positive predictive value (PPV) for different levels of TB prevalence. Screening for prolonged cough has low yield, 22% if confirmatory testing is by SSM and 32% if XP, and a high NNS, exceeding 1000 if TB prevalence is ≤0.5%. Due to low specificity the PPV of screening for any TB symptom followed by SSM is less than 50%, even if TB prevalence is 2%. CXR screening for TB abnormalities followed by XP has the highest case detection (87%) and lowest NNS, but is resource intensive. CXR as a second screen for symptom screen positives improves efficiency. The ideal algorithm does not exist. The choice will be setting specific, for which this study provides guidance. Generally an algorithm composed of CXR screening followed by confirmatory testing with XP can achieve the lowest NNS and highest PPV, and is the least amenable to setting-specific variation. However resource requirements for tests and equipment may be prohibitive in some settings and a reason to opt for symptom screening and SSM. To better inform disease control programs we need empirical data to confirm the modeled yield, cost-effectiveness studies, transmission models and a better screening test.


Respiratory function and treatment in dogs with acute respiratory distress syndrome: 19 cases (1985-1993).
To characterize respiratory function and treatment in dogs with findings compatible with those of human adult respiratory distress syndrome (ARDS) and to evaluate the application in dogs of clinical for diagnosis of ARDS. Retrospective review of medical records. 19 dogs with acute respiratory distress syndrome. Arterial blood pH was 7.30 +/- 0.59 (mean +/- SD). Nine dogs had metabolic acidosis. In nonmechanically ventilated dogs, PaCO2 was 15.0 to 54.9 mm of Hg. Respiratory acidosis developed in 2 mechanically ventilated dogs. Hypoxemia was observed in 4 of 5 dogs breathing room air. In 4 mechanically ventilated dogs, oxygenation was inadequate, despite use of > 60% inspired O2 and positive end-expiratory pressure in 3 dogs. Alveolar-to-arterial oxygen tension gradients were widened in 4 dogs breathing room air and in 6 dogs ventilated with 100% O2. Ten dogs were mechanically ventilated; ventilatory rate was 18 to 60 breaths/min. Tidal volume was 12 +/- 3.8 ml/kg of body weight in 4 dogs, minute ventilation > 400 ml/kg/min in 2 dogs, and peak airway pressures > 25 cm of H2O in 6 dogs. Positive end-expiratory pressure was used in 8 dogs. Pneumothorax was detected in 5 ventilated dogs. Human clinical criteria for diagnosis of ARDS were fulfilled in 7 dogs. Fluid treatment consisted of IV crystalloids and synthetic colloids. Drugs most often administered were antibiotics and loop diuretics. Human clinical criteria for identification of ARDS may be helpful in diagnosis of acute respiratory distress syndrome in dogs.


NISPLAN--projecting hospital beds and hospital stays.
The paper describes a computer model for projections of hospital stays and hospital beds, developed by NIS Health Services Research in Norway. The model takes into account demographic changes, changes in medical technology, needs for hospital services, morbidity and hospital structure and population preferences as to choice of hospital. It has been used in several projects in Norway, both by central and local authorities.


The Oral Risk Assessment and Early Intervention System--a clinician's tool for integrating the bio/psycho/social risk into oral disease interventions.
An association between oral diseases and systemic diseases has been suspected for centuries. More recently, investigation has provided insight into the impact of psychologic factors, social value systems, beliefs about disease processes and predictive treatment outcomes. Historically, dentistry has focused primarily on the restoration of physical function rather than broader multifactorial issues that impact long-term health maintenance. Dental patients are a complex interaction of biologic susceptibilities, lifestyle behaviors, values, and disease risk variables, which require an interdisciplinary approach to provide optimal health care. This article provides information-processing tools to assist clinicians in developing appropriate patient interventions by employing on Oral Risk Assessment and Early Intervention System.


Enhanced near-infrared absorption in graphene with multilayer metal-dielectric-metal nanostructure.
A multilayer metal-dielectric-metal nanostructure is proposed to enhance the absorption in graphene in a near-infrared region. The main feature of the structure is the generation of strong magnetic response within the dielectric spacer, which is directly related to absorption enhancement in graphene to over 22 times higher than that of free-standing monolayer graphene. We also show that absorption enhancement in graphene can be easily controlled by adjusting the geometry of the propose structure. The simple structural configuration and the flexible tunability in absorption enhancement are beneficial for practical fabrication and future applications in graphene-based active optoelectronic devices.


Semiconductor laser-induced fluorescence detection in picoliter volume flow cells.
A visible semiconductor laser-induced fluorescence detection system for ultratrace chemical analysis of nanoliter-to-picoliter samples is optimized and characterized in detail. With low-power semiconductor lasers emitting at 675 and 639 nm for excitation, the best limit of detection is 8000 molecules for a model fluorescent compound (1,1',3,3,3',3'-hexamethylindotricarbocyanine iodide) in an ethanol solution. Fused silica capillaries with inner diameters between 250 and 11 microm were employed as picoliter volume flow cells, which permits the use of the system in miniaturized separation techniques such as packed and open tubular liquid chromatography and capillary electrophoresis.


Inhibitory effect of natural phenolic lipids upon NAD-dependent dehydrogenases and on triglyceride accumulation in 3T3-L1 cells in culture.
Alkylresorcinols are phenolic lipids present at levels of 0.03-0.15% in wheat and rye grains and almost 10 times higher in respective bran products. Despite numerous studies on the influence of dietary fibers on the regulation of energy metabolism, this issue still remains controversial. The objective of our current studies was to investigate whether 5-n-alk(en)ylresorcinols, natural phenolic components of high fiber human diets, may be considered as natural regulators of excessive fat accumulation. Our studies revealed that 5-n-alk(en)ylresorcinols isolated from wheat and rye bran inhibit glycerol-3-phosphate dehydrogenase, the key enzyme in triglyceride synthesis in adipocytes, specifically and effectively. Further in vitro studies showed that these compounds also prevent triglyceride accumulation in 3T3-L1 cells. The most effective compound in both systems was 5-n-heneicosylresorcinol. The results indicate that the potential to prevent triglyceride accumulation increases with the hydrophobicity of the phenolic inhibitor.


Focal Accumulation of ROS Can Block Pyricularia oryzae Effector BAS4-Expression and Prevent Infection in Rice.
The reactive oxygen species (ROS) burst is the most common plant immunity mechanism to prevent pathogen infection, although the exact role of ROS in plant immunity has not been fully elucidated. We investigated the expression and translocation of Oryza sativa respiratory burst oxidase homologue B (OsRBOHB) during compatible and incompatible interactions between rice epidermal cells and the pathogenic fungus Pyricularia oryzae (syn. Magnaporthe oryzae). We characterized the functional role of ROS focal accumulation around invading hyphae during P. oryzae infection process using the OsRBOHB inhibitor diphenyleneiodonium (DPI) and the actin filament polymerization inhibitor cytochalasin (Cyt) A. OsRBOHB was strongly induced during incompatible rice-P. oryzae interactions, and newly synthesized OsRBOHB was focally distributed at infection sites. High concentrations of ROS focally accumulated at the infection sites and suppressed effector biotrophy-associated secreted (BAS) proteins BAS4 expression and invasive hyphal growth. DPI and Cyt A abolished ROS focal accumulation and restored P. oryzae effector BAS4 expression. These results suggest that ROS focal accumulation is able to function as an effective immune mechanism that blocks some effectors including BAS4-expression during P. oryzae infection. Disruption of ROS focal accumulation around invading hyphae enables successful P. oryzae colonization of rice cells and disease development.


Commode design for frail and disabled people.
Commode use carries a significant risk of falls for frail older people. Traditional commode design is often inadequate. Working with manufacturers can bring essential design changes.


Determinants of universal adolescent hepatitis B vaccine uptake.
The UK is currently considering the introduction of universal hepatitis B vaccination. This study of determinants of vaccine uptake among school based adolescents shows that living in areas of high deprivation, commonly associated with injecting drug risk behaviours, was the most important factor, with statistically significant lower odds of receiving three doses. This was less pronounced for receipt of two doses. Thus, there are implications for future policy; if universal vaccination is approved, a licensed two dose schedule would be most appropriate in this setting.


Development of a central auditory test battery for adults.
There is little standardized test material in Dutch to document central auditory processing disorders (CAPDs). Therefore, a new central auditory test battery was composed and standardized for use with adult populations and older children. The test battery comprised seven tests (words in noise, filtered speech, binaural fusion, sentences in noise, dichotic digits, frequency and duration patterns, backward masking) and a questionnaire. Descriptive statistics obtained from 28 Dutch adults with normal hearing are presented. Eleven of the subjects were retested. The test-retest results showed that the variability between subjects was not due to systematic effects. Except for the backward masking test, the results were comparable with data from other studies. As most test scores did not follow a normal distribution, cut-off scores are recommended to evaluate individual subjects. Experiments on subjects with suspected CAPDs are in progress to validate the test battery and to see whether the number of tests can be reduced.


A novel method of tunnel creation using intraoperative optical coherence tomography-guided deep anterior lamellar keratoplasty.
The big bubble technique has become the technique of choice for performing deep anterior lamellar keratoplasty (DALK) since its inception in 2002. The main challenge with this technique is in achieving a big bubble while preventing inadvertent perforation of the Descemet's membrane. Although femtosecond lasers have increased the safety, accuracy, and predictability of corneal dissection in DALK, the challenge of achieving a big bubble still exists. To overcome this challenge, Zeimer Z8 Femto LDV has launched a new software module for DALK, which has an added advantage of real-time optical coherence tomography-assisted femtosecond tunnel creation for achieving a big bubble.


Multi-Scale Nanoarchitectured Fibrous Networks for High-Performance, Self-Sterilization, and Recyclable Face Masks.
Airborne particulate matter (PM) pollutants, especially with nanoscale size, have caused serious public health issues. The global demand for high-performance and recyclable face masks is increasing dramatically, especially during the COVID-19 pandemic. However, present masks suffer from low-efficiency interception of PM0.3 /pathogen, limited air permeability, and incapacity to reuse and recycle. Here, multi-scale nanoarchitectured nanofiber/carbon nanotube (NF/CNT) networks are constructed by a needleless-electrospinning/spraying-netting strategy, enabling well-dispersed CNT networks (diameter ≈ 25 nm) welded on charged nanofibrous scaffolds (diameter > 100 nm) layer by layer. The optimized NF/CNT networks possess a fluffy structure with narrow-distribution small pores (size ≈ 400 nm), "free molecular flow" behavior, and electrostatic adsorption property, thereby exhibiting high filtration efficiency (>99.994% PM0.3 removal) and low resistance (<0.05% atmosphere pressure). Furthermore, they demonstrate reliable and ultra-fast photothermal-driven self-sterilization (>99.986% in 5 min) under 1 sun and electrothermal-driven self-sterilization (>99.9999% in 2 min) in sunless scenes owing to their unique nanoarchitecture. Most importantly, the abandoned NF/CNT filters can be fully recycled as high-performance solar vapor generators to desalinate seawater (3.56 L m-2 d-1 ). This work offers a fascinating solution to reduce disease transmission, resource consumption, and environmental burdens.


Double Whammy: Rare Case of Infected Chronic Seroma Due to Bacterial Translocation From Biliary Sepsis.
We present a case of infected chronic seroma post ventral hernia repair using the Rives-Stoppa technique likely from bacterial translocation from ascending cholangitis. After definitive treatment with endoscopic retrograde cholangiopancreatography (ERCP) and drainage of obstructed gallstones, she continued to show signs of sepsis. Percutaneous drainage of seroma was diagnostic for infection, where Escherichia coli (E. coli) was cultured and coupled with IV antibiotics, her infection was treated. To the best of our knowledge, this is the first case of seroma infection from biliary sepsis, and there are no cases of infected seroma from a secondary infection in the literature.


Polycrystalline Boron-doped Diamond Electrolyte-solution-gate Field-effect Transistor Applied to the Measurement of Water Percentage in Ethanol.
A polycrystalline diamond electrolyte-solution-gate field-effect transistor (BDD-SGFET) was successfully applied to the analysis of water content in ethanol. Due to the use of a no-gate-insulator FET, the developed sensor showed a four-times-faster response than the conventional Si-FET, and a ten-times-faster response than a glass electrode. The output voltage showed good linearity with respect to the water content. This result is of practical importance because the traditional water content measurement methods are impractical due to their slow response.


Increased transplanted organs from the use of a standardized donor management protocol.
The organ shortage has resulted in increasing recipient waiting lists and waiting-list deaths. The increased use of expanded donors has been associated with increased discarding of procured organs because of poor organ function. A structured donor management algorithm or critical pathway was tested to determine its effect on the donor management and procurement process. A pilot study examined donors from 88 critical care units in 10 organ procurement organizations managed under the critical pathway and compared them to retrospective data collected at those same pilot sites. The total number of organs both procured and transplanted per 100 donors was significantly greater (p <0.01) in the critical pathway group when compared to the control group. There was no significant difference in 1-year graft survival for any of the organs recovered, and no significant difference in the rate of delayed graft function in the kidneys transplanted. Use of a structured donor management algorithm results in significant increases in organs procured and organs transplanted without any reduction in the quality of the organs being transplanted.


A portable hand-held device for quantifying and standardizing tremor assessment.
We describe the results of a hand-held device for quantifying tremor in the upper extremity. The specific aims of the study were to evaluate: (1) the reliability of the device to record tremor frequency and amplitude; (2) the relationship between observer ratings of tremor severity and spectral power derived from the instrument; (3) the effects of limb posture on tremor properties recorded by the instrument; and (4) whether scores from the instrument can discriminate types of tremor with sufficient accuracy to be of diagnostic value. Results from 242 subjects with tremor showed significant effects of limb posture on tremor frequency detected by the device which could not be revealed using traditional observer severity ratings. Subjects with tremor associated with idiopathic Parkinson's disease were distinguished from patients with drug-induced parkinsonian tremor with 83% accuracy. These and other findings on instrument validity demonstrate that tremor assessment can be performed using standard quantitative procedures which overcome many of the limitations inherent in subjective observer ratings. The portability of this instrument, referred to as the Tremorometer, makes it a useful tool for multi-site collaborative studies in community settings.


A unified formalism for estimating photon absorbed fractions in spherical biovolumes: analytical equations without fitting parameters.
A new analytical formalism, previously developed for estimating electron-absorbed fractions, was extended for estimating photon absorbed fractions in soft-tissue spheres, containing uniformly distributed photon-emitter. Analytical equations were formulated for calculating values of photon-absorbed fractions. The method involves a rescaling procedure with transformation of real biological sizes to unitless effective ones, combining information of photon energy, object's size, and material. Rescaling was applied to large published datasets of photon absorbed fractions in soft-tissue spheres, computed with Monte Carlo codes. A new effect was demonstrated in which the rescaled data formed a single smooth 'unified curve' with saturation. The unified curve for photon absorbed fractions was described analytically, using simple equations without fitting parameters. The new method was tested for a wide range of spheres-from 1 mg up to 1000 kg, and wide range of photon energies-from 0.02 up to 5 MeV. For larger spheres, a close agreement between analytical values and Monte Carlo datasets was demonstrated. For small biovolumes, analytical equations predict higher values than available Monte Carlo data. The unified formalism is now available for direct calculating radiation absorbed fractions in soft-tissue spherical organs and organisms without Monte Carlo codes.


Guanidinylated polyethyleneimine-polyoxypropylene-polyoxyethylene conjugates as gene transfection agents.
Conjugates of linear and branched polyethyleneimine (PEI) and monoamine polyether Jeffamine M-2070 (PO/EO mol ratio 10/31, 2000 Da) were synthesized through polyether activation by cyanuric chloride followed by attachment to PEI and guanidinylation by 1H-pyrazole-carboxamidine hydrochloride. The resulting guanidinylated PEI-polyether conjugates (termed gPEI-Jeffamine) efficiently complexed plasmid DNA, and their polyplexes possessed enhanced colloidal stability in the presence of serum proteins. In vitro studies with mammalian CHO-1, 3T3, and Cos-7 cell lines demonstrated improved transfection efficiency of the pCMVbeta-gal plasmid/gPEI-Jeffamine polyplexes. The guanidinylation of the amino groups of PEI and the conjugation of PEI with the Jeffamine polyether enhanced the conjugates' interaction with genetic material and reduced the cytotoxicity of the polyplexes in experiments with the L929 cell line.


Visualization of semantic indexing similarity over MeSH.
We present an interactive visualization system for the evaluation of indexing results of the MEDLINE data-base over the Medical Subject Headings (MeSH) structure in a graphical radial-tree layout. It displays indexing similarity measurements with 2D color coding and a 3D height field permitting the evaluation of the automatic Medical Text Indexer (MTI), compared with human indexers.


HuD Binds to and Regulates Circular RNAs Derived From Neuronal Development- and Synaptic Plasticity-Associated Genes.
The RNA-binding protein (RBP) HuD is involved in neuronal differentiation, regeneration, synaptic plasticity and learning and memory. RBPs not only bind to mRNAs but also interact with several types of RNAs including circular RNAs (circRNAs), a class of non-coding RNAs generated by pre-mRNA back-splicing. This study explored whether HuD could regulate the expression of neuronal circRNAs. HuD controls target RNA's fate by binding to Adenylate-Uridylate Rich Elements (AREs). Using bioinformatics analyses, we found HuD-binding ARE-motifs in about 26% of brain-expressed circRNAs. By RNA immunoprecipitation (RIP) from the mouse striatum followed by circRNA arrays, we identified over 600 circRNAs bound to HuD. Among these, 226 derived from genes where HuD also bound to their associated mRNAs including circHomer1a, which we previously characterized as a synaptic HuD target circRNA. Binding of HuD to two additional plasticity-associated circRNAs, circCreb1, and circUfp2, was validated by circRNA-specific qRT-PCR. Interestingly, we found that circUpf2 is also enriched in synaptosomes. Pathway analyses confirmed that the majority of HuD-bound circRNAs originate from genes regulating nervous system development and function. Using striatal tissues from HuD overexpressor (HuD-OE) and knock out (KO) mice for circRNA expression analyses we identified 86 HuD-regulated circRNAs. These derived from genes within the same biological pathways as the HuD RIP. Cross-correlation analyses of HuD-regulated and HuD-bound circRNAs identified 69 regulated in either HuD-OE or HuD-KO and 5 in both sets. These include circBrwd1, circFoxp1, and circMap1a, which derive from genes involved in neuronal development and regeneration, and circMagi1 and circLppr4, originating from genes controlling synapse formation and linked to psychiatric disorders. These circRNAs form competing endogenous RNA (ceRNA) networks including microRNAs and mRNAs. Among the HuD target circRNAs, circBrwd1 and circFoxp1 are regulated in an opposite manner to their respective mRNAs. The expressions of other development- and plasticity-associated HuD target circRNAs such as circSatb2, cirHomer1a and circNtrk3 are also altered after the establishment of cocaine conditioned place preference (CPP). Collectively, these data suggest that HuD interactions with circRNAs regulate their expression and transport, and that the ensuing changes in HuD-regulated ceRNA networks could control neuronal differentiation and synaptic plasticity.


UDP-arabinopyranose mutase gene expressions are required for the biosynthesis of the arabinose side chain of both pectin and arabinoxyloglucan, and normal leaf expansion in Nicotiana tabacum.
Plant cell walls are composed of polysaccharides such as cellulose, hemicelluloses, and pectins, whose location and function differ depending on plant type. Arabinose is a constituent of many different cell wall components, including pectic rhamnogalacturonan I (RG-I) and II (RG-II), glucuronoarabinoxylans (GAX), and arabinoxyloglucan (AXG). Arabinose is found predominantly in the furanose rather than in the thermodynamically more stable pyranose form. The UDP-arabinopyranose mutases (UAMs) have been demonstrated to convert UDP-arabinopyranose (UDP-Arap) to UDP-arabinofuranose (UDP-Araf) in rice (Oryza sativa L.). The UAMs have been implicated in polysaccharide biosynthesis and developmental processes. Arabinose residues could be a component of many polysaccharides, including branched (1→5)-α-arabinans, arabinogalactans in pectic polysaccharides, and arabinoxyloglucans, which are abundant in the cell walls of solanaceous plants. Therefore, to elucidate the role of UAMs and arabinan side chains, we analyzed the UAM RNA interference transformants in tobacco (Nicotiana tabacum L.). The tobacco UAM gene family consists of four members. We generated RNAi transformants (NtUAM-KD) to down-regulate all four of the UAM members. The NtUAM-KD showed abnormal leaf development in the form of a callus-like structure and many holes in the leaf epidermis. A clear reduction in the pectic arabinan content was observed in the tissue of the NtUAM-KD leaf. The arabinose/xylose ratio in the xyloglucan-rich cell wall fraction was drastically reduced in NtUAM-KD. These results suggest that UAMs are required for Ara side chain biosynthesis in both RG-I and AXG in Solanaceae plants, and that arabinan-mediated cell wall networks might be important for normal leaf expansion.


Segmentation and volume quantification of epicardial adipose tissue in computed tomography images.
Many cardiovascular diseases are closely related to the composition of epicardial adipose tissue (EAT). Accurate segmentation of EAT can provide a reliable reference for doctors to diagnose the disease. The distribution and composition of EAT often have significant individual differences, and the traditional segmentation methods are not effective. In recent years, deep learning method has been gradually introduced into EAT segmentation task. The existing EAT segmentation methods based on deep learning have a large amount of computation and the segmentation accuracy needs to be improved. Therefore, the purpose of this paper is to develop a lightweight EAT segmentation network, which can obtain higher segmentation accuracy with less computation and further alleviate the problem of false-positive segmentation. First, the obtained computed tomography was preprocessed. That is, the threshold range of EAT was determined to be -190, -30 HU according to prior knowledge, and the non-adipose pixels were excluded by threshold segmentation to reduce the difficulty of training. Second, the image obtained after thresholding was input into the lightweight RDU-Net network to perform the training, validating, and testing process. RDU-Net uses a residual multi-scale dilated convolution block in order to extract a wider range of information without changing the current resolution. At the same time, the form of residual connection is adopted to avoid the problem of gradient expansion or gradient explosion caused by too deep network, which also makes the learning easier. In order to optimize the training process, this paper proposes PNDiceLoss, which takes both positive and negative pixels as learning targets, fully considers the class imbalance problem, and appropriately highlights the status of positive pixels. In this paper, 50 CCTA images were randomly selected from the hospital, and the commonly used Dice similarity coefficient (DSC), Jaccard similarity, accuracy (ACC), specificity (SP), precision (PC), and Pearson correlation coefficient are used as evaluation metrics. Bland-Altman analysis results show that the extracted EAT volume is consistent with the actual volume. Compared with the existing methods, the segmentation results show that the proposed method achieves better performance on these metrics, achieving the DSC of 0.9262. The number of false-positive pixels has been reduced by more than half. Pearson correlation coefficient reached 0.992, and linear regression coefficient reached 0.977 when measuring the volume of EAT obtained. In order to verify the effectiveness of the proposed method, experiments are carried out in the cardiac fat database of VisualLab. On this database, the proposed method also achieved good results, and the DSC value reached 0.927 in the case of only 878 slices. A new method to segment and quantify EAT is proposed. Comprehensive experiments show that compared with some classical segmentation algorithms, the proposed method has the advantages of shorter time-consuming, less memory required for operations, and higher segmentation accuracy. The code is available at https://github.com/lvanlee/EAT_Seg/tree/main/EAT_seg.


Cyst Formation from Virulent RH Strain of Toxoplasma gondii Tachyzoite: In Vitro Cultivation.
This study was performed to induce conversion of RH strain tachyzoites of Toxoplasma gondii to bradyzoites by pH changing of the culture medium. HeLa cell monolayers were infected at a 1:1 tachyzoite to cell ratio. Four hours after infection, the culture medium was removed and replaced with culture medium and 5% FCS, adjusted to pH 8 with NaOH. The culture was maintained at 37 °C without CO2 until the end of the experiment. Cyst-like structures were collected and stained with periodic acid schiff (PAS) staining method. The soluble antigens of cyst-like structures of RH strain, in addition to RH tachyzoite, bradyzoites of avirulent Tehran strain and uninfected HeLa cells were electrophoresed on 12.5% polyacrylamide gel. The gel was stained by coomassie brilliant blue R-250. Four days after infection of HeLa cells with tachyzoites of T. gondii, RH strain, cyst- like structures were noticed and stained with PAS. In the SDS-PAGE, protein bands of these structures had some differences with tachyzoites of RH strain, but there was quite similarity between protein bands of these structures and tissue cysts (bradyzoites) of Tehran strains. P34 and P36 (bradyzoite-specific proteins) were observed only in T. gondii bradyzoites of RH (cyst like structures) and bradyzoites of Tehran strains. Alkalization of culture medium to pH 8 induced expression of bradyzoite- specific proteins and production of RH cysts in cell culture.


A complete carbon-nanotube-based on-chip cooling solution with very high heat dissipation capacity.
Heat dissipation is one of the factors limiting the continuous miniaturization of electronics. In the study presented in this paper, we designed an ultra-thin heat sink using carbon nanotubes (CNTs) as micro cooling fins attached directly onto a chip. A metal-enhanced CNT transfer technique was utilized to improve the interface between the CNTs and the chip surface by minimizing the thermal contact resistance and promoting the mechanical strength of the microfins. In order to optimize the geometrical design of the CNT microfin structure, multi-scale modeling was performed. A molecular dynamics simulation (MDS) was carried out to investigate the interaction between water and CNTs at the nanoscale and a finite element method (FEM) modeling was executed to analyze the fluid field and temperature distribution at the macroscale. Experimental results show that water is much more efficient than air as a cooling medium due to its three orders-of-magnitude higher heat capacity. For a hotspot with a high power density of 5000 W cm(-2), the CNT microfins can cool down its temperature by more than 40 °C. The large heat dissipation capacity could make this cooling solution meet the thermal management requirement of the hottest electronic systems up to date.


On the Red Antenna States of Photosystem I Mutants from Cyanobacteria Synechocystis PCC 6803.
To identify the molecular composition of the low-energy states in cyanobacterial Photosystem I (PSI) of Synechocystis PCC6803, we focus on high-resolution (low-temperature) absorption, emission, resonant, and nonresonant hole-burned spectra obtained for wild-type (WT) PSI and three PSI mutants. In the Red_a mutant, the B33 chlorophyll (Chl) is added to the B31-B32 dimer; in Red_b, histidine 95 (His95) on PsaB (which coordinates Mg in the B7 Chl within the His95-B7-A31-A32-cluster) is replaced with glutamine (Gln), while in the Red_ab mutant, both mutations are made. We show that the C706 state (B31-B32) changes to the C710 state (B31-B32-B33) in both Red_a and Red_ab mutants, while the C707 state in WT Synechocystis (localized on the His95-B7-A31-A32 cluster) is modified to C716 in both Red_b and Red_ab. Excitation energy transfer from C706 to the C714 trap in the WT PSI and Red_b mutant is hampered as reflected by a weak emission at 712 nm. Large electron-phonon coupling strength (exposed via resonant hole-burned spectra) is consistent with a strong mixing of excited states with intermolecular charge transfer states leading to significantly red-shifted emission spectra. We conclude that excitation energy transfer in PSI is controlled by fine-tuning the electronic states of a small number of highly conserved red states. Finally, we show that mutations modify the protein potential energy landscape as revealed by different shapes and shifts of the blue- and red-shifted antiholes.


Cytochrome P450 2A5 and bilirubin: mechanisms of gene regulation and cytoprotection.
Bilirubin (BR) has recently been identified as the first endogenous substrate for cytochrome P450 2A5 (CYP2A5) and it has been suggested that CYP2A5 plays a major role in BR clearance as an alternative mechanism to BR conjugation by uridine-diphosphate glucuronyltransferase 1A1. This study investigated the mechanisms of Cyp2a5 gene regulation by BR and the cytoprotective role of CYP2A5 in BR hepatotoxicity. BR induced CYP2A5 expression at the mRNA and protein levels in a dose-dependent manner in primary mouse hepatocytes. BR treatment also caused nuclear translocation of Nuclear factor-E2 p45-related factor 2 (Nrf2) in hepatocytes. In reporter assays, BR treatment of primary hepatocytes transfected with a Cyp2a5 promoter-luciferase reporter construct resulted in a 2-fold induction of Cyp2a5 reporter activity. Furthermore, cotransfection of the hepatocytes with a Nrf2 expression vector without BR treatment resulted in an increase in Cyp2a5 reporter activity of approximately 2-fold and BR treatment of Nrf2 cotransfectants further increased reporter activity by 4-fold. In addition, site-directed mutation of the ARE in the reporter construct completely abolished both the BR- and Nrf2-mediated increases in reporter activity. The cytoprotective role of CYP2A5 against BR-mediated apoptosis was also examined in Hepa 1-6 cells that lack endogenous CYP2A5. Transient overexpression of CYP2A5 partially blocked BR-induced caspase-3 cleavage in Hepa 1-6 cells. Furthermore, in vitro degradation of BR was increased by microsomes from Hepa 1-6 cells overexpressing CYP2A5 compared to control cells transfected with an empty vector. Collectively, these results suggest that Nrf2-mediated CYP2A5 transactivation in response to BR may provide an additional mechanism for adaptive cytoprotection against BR hepatotoxicity.


Helicobacter pylori: bacterial strategy for incipient stage and persistent colonization in human gastric niches.
Helicobacter pylori (H. pylori) undergoes decades long colonization of the gastric mucosa of half the population in the world to produce acute and chronic gastritis at the beginning of infection, progressing to more severe disorders, including peptic ulcer disease and gastric cancer. Prolonged carriage of H. pylori is the most crucial factor for the pathogenesis of gastric maladies. Bacterial persistence in the gastric mucosa depends on bacterial factors as well as host factors. Herein, the host and bacterial components responsible for the incipient stages of H. pylori infection are reviewed and discussed. Bacterial adhesion and adaptation is presented to explain the persistence of H. pylori colonization in the gastric mucosa, in which bacterial evasion of host defense systems and genomic diversity are included.


Post-transplant lymphoproliferative disorders and Epstein-Barr virus DNAemia in a cohort of lung transplant recipients.
Post-transplant lymphoproliferative disorders (PTLD) are serious complications in lung transplant recipients. No consensus on EBV DNAemia levels predictive of PTLD has been reached. In addition, in many instances EBV DNAemia is determined in patients with suggestive symptoms only. The characteristics of five patients with PTLD as well as the prevalence of EBV DNAmia in a cohort of 137 consecutive patients receiving lung transplantation are described. Twenty-six out of 137 patients (18.9%) were excluded from the analysis because lost at follow-up or dead from PTLD-independent reasons within three months of transplantation. EBV DNA in peripheral blood mononuclear cells (PBMC) was determined in 83/111 patients (74.8%) because of potential PTLD-related symptoms, while 28 patients (25.2%) showed no symptoms and were not examined. EBV DNAemia was positive in 53/83 patients (63.8%), and negative in 30/83 patients (36.2%). PTLD was diagnosed in five (4.5%) patients at a median time of 270 (range 120-870) days following transplantation. All five PTLD (three large B-cell lymphomas, one Hodgkin lymphoma and one possible pre-neoplastic lesion) were potentially associated with EBV infection. However, only 3/5 patients with PTLD had detectable EBV DNAemia: < 1,000 copies EBV DNA/1 × 10⁵ PBMC in one patient and > 1,000 copies EBV DNA/1 × 10⁵ PBMC in two patients. A systematic multidisciplinary (clinical, radiologic, virologic and histologic) approach is mandatory for the diagnosis and management of PTLD in lung transplant recipients, while monitoring of symptomatic patients only may provide an incomplete or late picture of the clinical problem. In addition, staining for EBV antigens and quantification of EBV DNA in biopsy specimens should always be performed to understand the role of EBV infection in the pathogenesis of PTLD.


The effectiveness of helplines for the treatment of alcohol and illicit substance use.
While tobacco helplines (quitlines) are thought to be effective, helplines which treat other substance use do not have an established evidence base. A review was conducted of the literature on illicit drug or alcohol (IDA) helplines. The literature search was conducted in five databases. Studies prior to 2014 were included if published in English, and involved the use of a telephone counselling helpline for the treatment of illicit drug or alcohol use. Review papers, opinion pieces, letters or editorials, case studies, published abstracts and posters were excluded. Initial searching identified 2178 articles and after removing duplicates and those meeting the exclusion criteria, there were 36 publications for review. A total of 29 articles provided descriptive information about 19 different IDA helplines which operated in the US (42%), Europe (21%), Australia (21%), Asia (11%) and Canada (5%). These services reported monthly call rates from 3.7 to over 23,000 calls per month. A total of nine articles provided evaluative information on eight different IDA helplines: four articles included a comparison of treatment outcomes against a control group and five articles included information on treatment satisfaction or service utilisation. Together they provide some evidence that these services are effective. Although there was little consistency in the measures used between articles which assessed helpline satisfaction, all but one reported high satisfaction. Although the evidence is mainly supportive of IDA helplines, further work is required to compare treatment outcomes in randomized groups.


Chemical dependency in students with and without learning disabilities.
To determine if students with learning disabilities (LD) demonstrate a higher frequency of chemical dependency than students without learning disabilities (NLD), a total of 191 adolescents with LD (101 males and 90 females) were given the Substance Abuse Subtle Screening Inventory (SASSI). The sample consisted of 88 students with LD and 103 NLD students between the ages of 12 and 18. The SASSI is an objectively scored self-report inventory that accurately classifies adolescents as chemically dependent (CD) or not chemically dependent (NCD). A significantly higher proportion of students with LD than NLD students were classified as CD. Of the 30 students who were classified as CD, 70% were students with LD. A discriminant analysis indicated that the presence or absence of a learning disability was a better predictor of classification as CD or NCD than gender, ethnicity, age, socioeconomic status, or family composition. The implications for evaluation and educational planning for students with learning disabilities are discussed.


Experimental evidence and DFT studies of next-nearest-neighbor magnetic interactions through diamagnetic 3d and 4d ions.
The copper template effect allows the preparation of tridentate ligands that chelate copper ions, leaving unoccupied the fourth basal coordination position and at least one axial position of the copper coordination polyhedron. Two such cationic complexes, [LCu](+) and [L(1)Cu](+) (L(-) = 2-{(E)-[(2-aminoethyl)imino]methyl}phenoxo] and L(1-) = 2-{(E)-[(2-aminopropyl)imino]methyl}phenoxo), react with diamagnetic polycyanometalate tectons such as Ni(CN)(4)(2-) or Ag(CN)(2)(-) to yield different neutral 1D complexes. In {[(LCu)(2)Ni(CN)(4)]}(n) (1) the four cyano nitrogen atoms are involved in coordination with copper ions in such a manner that each copper atom is pentacoordinated and linked to two cyano functions that occupy axial and equatorial coordination positions. Two L(1)Cu(+) cationic entities are linked, through their equatorial plane, to two trans cyano groups of the Ni(CN)(4)(2-) tecton in complex [(L(1)Cu)(2)Ni(CN)(4)] (2), the two uncoordinated cyano groups being involved in hydrogen bonds. 2 is a racemate, a S stereoisomer being associated with a R one in each [(L(1)Cu)(2)Ni(CN)(4)] unit. Zigzag Cu-Ag chains are present in [(LCu)Ag(CN)(2)] (3), where the copper centers are pentacoordinated and connected to the cyano groups in an alternate axial-equatorial coordination scheme. A bidimensional structure is developed by interchain argentophilic interactions. In complex 4, {(L(1)CuMeOH)(L(1)Cu)[Ag(CN)(2)](2)}, two L(1)Cu units are connected by a NC-Ag-CN bridge in an equatorial position. These resulting units exhibit argentophilic interactions with [Ag(CN(2))](-) entities that are monocoordinated in the equatorial position to the next unit, ultimately leading to a chain. Weak Cu-Cu magnetic interactions are detected in the four compounds, antiferromagnetic in the case of equatorial-equatorial copper interactions, ferromagnetic for orthogonal interacting copper orbitals (axial-equatorial interactions), while axial-axial bridges are characterized by an absence of interaction. The presence of weak ferromagnetic interactions through large NC-Ni-CN or NC-Ag-CN bridges (Cu···Cu distances larger than 10 Å) furnishes experimental evidence for the existence of next-nearest-neighbor interactions through diamagnetic centers. DFT calculations do confirm the existence of these magnetic transmission pathways through the diamagnetic metal bridge.


Precision spectroscopy using a partially stabilized frequency comb.
We present a simple method for precision spectroscopy using an optical frequency comb. One mode of a 1 GHz repetition rate mode-locked Ti:sapphire laser is offset-locked to an Rb-stabilized diode laser. This partially stabilized frequency comb stays locked, unattended, for hours at a time. Using the measured offset frequency and repetition rate, we calculate the frequency of each comb mode with absolute uncertainty of about 10 kHz in a 10 s measurement window. We demonstrate the capabilities and limitations of this approach with measurements in Rb, Cs, and Ca.


Workplace strategies for the control of work-related risks.
The prevention of work-related diseases and disorders, including those of neuropsychobehavioral nature, calls for integrated action to improve both job content and the working environment. Recent international labor standards have highlighted the importance of a good safety and health management system that ensures the assessment of risks and the appropriate control of these risks. Internationally, programs to cope with work-related risks place an increasing emphasis on participatory management of preventive measures, practical methods of risk assessment, and immediate improvements with the support of action-oriented training and information. Psychosocial factors, work performance, and job content need special attention. Workplace strategies must be developed by active participation of employers and workers, with their informed consent. These strategies and linked training activities should build on local practice and achievements rather than administrative models and be geared to the real local needs. In coping with the neurobehavioral effects, international sharing of positive experiences is useful especially with respect to: (i) providing information on potential neurobehavioral effects including labeling, safety datasheets, and precautions; (ii) providing practical advice about locally achieved improvements; (iii) providing action-oriented training; and (iv) creating opportunities for participatory workplace improvements.


Hand-raising a spectral tarsier (Tarsius tarsier) at the Ueno Zoological Gardens.
On February 10, 2008, a newborn male spectral tarsier (Tarsius tarsier) was found on the floor of the indoor exhibit room in the Small Mammal House of the Ueno Zoological Gardens. The dam showed no signs of providing maternal care and therefore we decided to hand-raise the infant. Its birth weight was 18.7 g. We placed the dam and infant in an incubator and gave 12.5-25% formula (for kittens), until the 145th day after birth. We limited the volume of formula intake to avoid excessive intake and to prevent diarrhea. For nutrition enrichment, we added a chicken liver homogenate to the formula 1-3 times per day. The infant was given a sunbath for 10 min on the 28th day. He showed no serious decline in health, except for diarrhea that occurred during the first few days after birth. He ate a small cricket for the first time on the 50th day and easily caught mealworms on his own on the 105th day. Gradual changes in feeding times, formula concentration, and the nutritionally enriched formula were essential for successfully hand-raising the tarsier.


The dynamics of meaningful social interactions and the emergence of collective knowledge.
Collective knowledge as a social value may arise in cooperation among actors whose individual expertise is limited. The process of knowledge creation requires meaningful, logically coordinated interactions, which represents a challenging problem to physics and social dynamics modeling. By combining two-scale dynamics model with empirical data analysis from a well-known Questions &Answers system Mathematics, we show that this process occurs as a collective phenomenon in an enlarged network (of actors and their artifacts) where the cognitive recognition interactions are properly encoded. The emergent behavior is quantified by the information divergence and innovation advancing of knowledge over time and the signatures of self-organization and knowledge sharing communities. These measures elucidate the impact of each cognitive element and the individual actor's expertise in the collective dynamics. The results are relevant to stochastic processes involving smart components and to collaborative social endeavors, for instance, crowdsourcing scientific knowledge production with online games.


Signal-averaging ECGs: an update.
ECRI has recently received many inquiries about ECG signal averaging and its clinical applications. The following report examines the current applications and state of development of this rapidly evolving technology.


Chrono-optimization of the time of evening administration with unequally divided twice-daily theophylline.
The effect of different times of evening administration (2000 hr versus 2200 hr) of sustained-release aminophylline (Euphyllin CR) on pharmacokinetics and lung functions was investigated in 30 patients presenting with moderately severe asthma. The study protocol followed a randomized three-period change-over design including a placebo period. As the dosing of the investigated SR-formulation is circadian rhythm adapted, the major part of the daily dose, namely 2/3, is affected by the change in time of administration. With regard to the nocturnal peak expiratory flow (PEF), no statistically significant difference between the times of evening administration was detected. However, the concomitant requirement for corticosteroids and inhaled beta-2-mimetics complicates the assessment of the relative clinical efficacy of the major dosing of theophylline during the 24 hr even though this drug is usually not given as a monotherapy in severe patients with reversible airway obstruction.


Self-assembled double ladder structure formed inside carbon nanotubes by encapsulation of H8Si8O12.
Unique low-dimensional SiO(2)-based nanomaterials can be encapsulated and synthesized inside the nanometer-scale one-dimensional internal spaces of carbon nanotubes (CNTs). In this study, various single-walled CNTs (SWNTs) and double-walled CNTs (DWNTs) having different diameters are used as containers for cubic octameric H(8)Si(8)O(12) molecules. High-resolution transmission electron microscopy (HRTEM), Fourier transform infrared (FT-IR) spectroscopy, and Raman spectroscopy observations revealed that, depending on the diameter of the CNTs, two types of structures are formed inside the SWNTs and DWNTs: In the case of those CNTs having inner diameters ranging from 1.2 to 1.4 nm, a new ordered self-assembled structure composed of H(8)Si(4n)O(8n-4) molecules was formed through the transformation of H(8)Si(8)O(12); however, in the case of CNTs having inner diameters larger than 1.7 nm, a disordered structure was formed. This behavior may indicate that strong interactions occur between the CNTs and the encapsulated H(8)Si(4n)O(8n-4) molecules.


Vitamin B-6 deficiency alters rat enterocyte calcium homeostasis but not duodenal transport.
Isolated enterocytes were used as differential transporting cells to examine calcium homeostasis in control and vitamin B-6-deficient rats. Kinetic analysis of calcium fluxes, as well as biochemical determinations, indicated that enterocytes from control animals had high concentrations of cytosol ionized calcium (318.5 +/- 22.4 nmol/L) and a large pool of exchangeable calcium (2.72 nmol/mg protein, or 86% of total cell calcium). Vitamin B-6 deficiency resulted in a 44% reduction in total cellular calcium (1.71 +/- 0.24 vs. 3.07 +/- 0.29 nmol/mg protein), a 69% reduction in total exchangeable calcium (0.85 vs. 2.72 nmol/mg protein) and a 56% reduction in cytosol ionized calcium concentration (141.4 +/- 13.5 vs. 318.5 +/- 22.4 nmol/L). Calcium fluxes between all cellular compartments were markedly diminished as a result of vitamin B-6 deficiency. However, vitamin B-6 deficiency did not affect the basic morphological or functional features of the enterocytes, such as cell viability, cell volume, membrane permeability and protein content. Moreover, intestinal calcium transport in vivo was not affected during vitamin B-6 deficiency, perhaps due to the greater paracellular ion movement compensating for the lower transcellular transport.


Variability over 1 week in the urinary concentrations of metabolites of diethyl phthalate and di(2-ethylhexyl) phthalate among eight adults: an observational study.
Phthalates are metabolized and eliminated in urine within hours after exposure. Several reports suggest that concentrations of phthalate metabolites in a spot urine sample can provide a reliable estimation of exposure to phthalates for up to several months. We examined inter- and intraperson and inter- and intraday variability in the concentrations of monoethyl phthalate (MEP), the major metabolite of diethyl phthalate, commonly used in personal care products, and mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), a metabolite of di(2-ethylhexyl) phthalate (DEHP), a polyvinyl chloride plasticizer of which diet is the principal exposure source, among eight adults who collected all urine voids (average, 7.6 samples/person/day) for 1 week. We analyzed the urine samples using online solid-phase extraction coupled to isotope dilution-high-performance liquid chromatography-tandem mass spectrometry. Regardless of the type of void (spot, first morning, 24-hr collection), for MEP, interperson variability in concentrations accounted for > 75% of the total variance. By contrast, for MEHHP, within-person variability was the main contributor (69-83%) of the total variance. Furthermore, we observed considerable intraday variability in the concentrations of spot samples for MEHHP (51%) and MEP (21%). MEP and MEHHP urinary concentrations varied considerably during 1 week, but the main contributors to the total variance differed (interday variability, MEHHP; interperson variability, MEP) regardless of the sampling strategy (spot, first morning, 24-hr collection). The nature of the exposure (diet vs. other lifestyle factors) and timing of urine sampling to evaluate exposure to phthalates should be considered. For DEHP and phthalates to which people are mostly exposed through diet, collecting 24-hr voids for only 1 day may not be advantageous compared with multiple spot collections. When collecting multiple spot urine samples, changing the time of collection may provide the most complete approach to assess exposure to diverse phthalates.


Simultaneous measurement of refractive index and temperature based on intensity demodulation using matching grating method.
A solution refractive index (SRI) and temperature simultaneous measurement sensor with intensity-demodulation system based on matching grating method were demonstrated. Long period grating written in a photonic crystal fiber (LPG-PCF), provides temperature stable and wavelength dependent optical intensity transmission. The reflective peaks of two fiber Bragg gratings (FBGs), one of which is etched then sensitive to both SRI and temperature, another (FBG2) is only sensitive to temperature, were located in the same linear range of the LPG-PCF's transmission spectrum. An identical FBG with FBG2 was chosen as a matching FBG. When environments (SRI and temperature) change, the wavelength shifts of the FBGs are translated effectively to the reflection intensity changes. By monitoring output lights of unmatching and matching paths, the SRI and temperature were deduced by a signal processing unit. Experimental results show that the simultaneous refractive index and temperature measurement system work well. The proposed sensor system is compact and suitable for in situ applications at lower cost.


Prognostic value of Hanifin and Rajka's feature sets in adult atopic dermatitis patients.
Prognostication of the course of atopic dermatitis (AD) is of special importance in prophylaxis of this disease. The aim of the study was to describe the AD minor feature sets, according to Hanifin and Rajka, on the basis of which one can predict the occurrence of extensive skin lesions, allergic rhinitis, atopic bronchial asthma, cataracts, hand and/or foot dermatitis, food intolerance, urticaria and elevated IgE serum in AD patients. Two-hundred-fifty-four patients were included in the study. Minor feature sets of prognostic value were selected using the MANOVA method in conjunction with the discriminant analysis. On the basis of the above sets, one can predict: involvement of more than 60% of body surface, occurrence of allergic rhinitis, elevated serum IgE, cataracts, atopic bronchial asthma, food intolerance and urticaria with the probability ratio of 90.8%, 82.8%, 79.9%, 78.4%, 77.3%, 77.1% and 76.1% respectively. In the examined group, no association was found between hand and/or foot dermatitis and the tendency towards skin infection.


The relationship between ventricular electrical delay and left ventricular remodelling with cardiac resynchronization therapy.
The aim of the present study was to evaluate the relationship between left ventricular (LV) electrical delay, as measured by the QLV interval, and outcomes in a prospectively designed substudy of the SMART-AV Trial. This was a multicentre study of patients with advanced heart failure undergoing cardiac resynchronization therapy (CRT) defibrillator implantation. In 426 subjects, QLV was measured as the interval from the onset of the QRS from the surface ECG to the first large peak of the LV electrogram. Left ventricular volumes were measured by echocardiography at baseline and after 6 months of CRT by a blinded core laboratory. Quality of life (QOL) was assessed by a standardized questionnaire. When separated by quartiles based on QLV duration, reverse remodelling response rates (>15% reduction in LV end systolic volume) increased progressively from 38.7 to 68.4% and QOL response rate (>10 points reduction) increased from 50 to 72%. Patients in the highest quartile of QLV had a 3.21-fold increase (1.58-6.50, P = 0.001) in their odds of a reverse remodelling response after correcting for QRS duration, bundle branch block type, and clinical characteristics by multivariate logistic regression analysis. Electrical dyssynchrony, as measured by QLV, was strongly and independently associated with reverse remodelling and QOL with CRT. Acute measurements of QLV may be useful to guide LV lead placement.


Dissection of evolutionary networks to assess their role in the evolution of robustness, function, and diversification.
Biological systems are remarkably robust in the face of environmental, mutational, and developmental perturbations. Analyses of molecular networks reveal recurrent features, such as modularity, that have been implicated in robustness and evolvability. Multiple theoretical models account for these features, yet few empirical tests of these models exist. Here I develop a set of broadly applicable methodologies to enable expanded empirical evaluation of model predictions. The methodologies focus on the inference and analysis of networks that depict evolutionary correlations among characters. I apply these methodologies to analyze an evolutionary network at a larger scale of organization among 42 stem anatomical and morphological characters of 52 species in the genus Adenia (Passifloraceae). I evaluate a model predicting that modular evolutionary networks will evolve in response to environmental change. The evolutionary network of Adenia is modular and "small-world," and the three diagnosed modules correspond roughly to functions of transport, storage, and mechanical support. The phylogenetically informed analyses suggest that the storage module is more impacted by environmental change than expected by chance. These results corroborate the hypothesis that modularity reduces the impact of environmental change, but this result requires further empirical evaluation that can be aided by the proposed methods in additional study systems.


Social and economic factors responsible for environmental performance: A global analysis.
Several factors influence the environmental performance simultaneously but ethnic fractionalization, political freedom, financial development and institutional quality have a substantial impact to explain the environmental performance across economies. This study focuses to explore that how environmental performance is affected by these economic, political and social indicators by using the annual data of 163 developed and developing countries covering the time period of 1996-2016.The data is collected from World Development Indicators, World Governance Indicators, Freedom House and Cline Centre. The stationarity of variables is analyzed through LLC, IPS and ADF Fisher Chi-square test. Before applying panel ARDL approach to find out the long run relationship among variables, order of integration is determined through Pedroni's cointegration test. The findings of study highlight that ethnic diversity; institutional quality and political freedom play a significant role to decrease CO2emissions while energy consumption, GDP growth and financial development are increasing the environmental degradation. Ethnic diversity is a source of creative and innovative approaches about problem solving of environmental degradation. Political freedom allows people to participate in decision making that posits much compliance with environmental agreements. The foreign direct investment is attracted by good quality institutions which cause to advent of more environment friendly technology along with attractions for further innovations that may helpful to reduce CO2 emissions. Contrary, GDP growth, financial development and energy consumption enhance the industrialization and urbanization leading to increase the level of CO2 emissions. It is suggested for policy makers that cohesion among different ethnic groups; improving institutional quality; providing political freedom to people and inclusive financial sector will acknowledge the less pollutant environment.


Effect of feeding clofibrate-containing diet on the hepatic NAD+ level in rats.
Feeding rats with a diet containing 0.25% clofibrate for 2 weeks elevated the hepatic NAD+ and total nicotinate levels significantly. Other peroxisome proliferators, such as 2-(4-chlorophenoxy)propionic acid and di(2-ethylhexyl)phthalate, had similar effects. When rats were fed the control diet without clofibrate for 1 week after 2 weeks of the clofibrate diet, the hepatic NAD+ level returned to the control value. Muscular NAD+ content was not affected by the peroxisome proliferators. The results were discussed in relation to induction of peroxisomal beta-oxidation enzymes by the peroxisome proliferators.


Virus-induced interferon production in human leukocytes: a low responder to one virus can be a high responder to another virus.
We measured the amounts of interferon (IFN) induced by four wild-type strains and two attenuated vaccine strains of poliovirus, testing each virus in 12-58 separate batches of human peripheral blood leukocytes. There were big and consistent differences in the mean amounts of IFN formed by leukocytes from different donors in response to all these polioviruses. Almost invariably, the wild-type polioviruses gave rise to more IFN than the corresponding attenuated strains, but overall, the amounts induced by one strain of poliovirus were proportional to those induced by another. There were indications of similar correlations with six different influenza viruses and with three strains of herpes simplex virus. In contrast, there was no correlation between the IFN yields induced with a poliovirus, three other enteroviruses, and various other viruses. These results suggest that the leukocytes from a given individual have a capacity to form IFN in vitro that is determined both by the genetic make-up of that individual and the particular virus concerned. If the same phenomenon applies to IFN production by cells in vivo, it may have a role in pathogenesis of viral infections.


Restorative care for palliative patients: a retrospective clinical audit of outcomes for patients admitted to an inpatient palliative care unit.
Restorative care in palliative care is a subset of rehabilitation that aims to improve quality of life through restoration or maintenance of physical functions. Outcomes for restorative care programmes delivered by palliative care units have not adequately been assessed. The objectives are to examine the outcomes of a restorative care programme in an inpatient palliative care unit, including discharge destination, performance status changes and length of stay. Retrospective clinical audit of consecutive patients admitted to Calvary Health Care Bethlehem in Melbourne, Australia, principally for restorative care from July 2010 to December 2011. 79 admissions met inclusion criteria. Mean age was 76.5 years (SD=11.14) and 43 (54%) were men. 75 (95%) patients had a malignant diagnosis; of these, the majority had lung cancer (24%). 16 patients (20%) were discharged home, 51 (65%) died and 12 (15%) were transferred. Of the patients discharged home, only 6 (38% of those discharged home) improved their performance status. Those discharged home had a significantly shorter length of stay (17 days compared to 39 days; p<0.05). Patients discharged home also had significantly better Australia-modified Karnofsky Performance Status (AKPS) and Resource Utilisation Groups-Activities of Daily Living (RUG-ADL) scores on admission than others (both p<0.05). The majority of patients referred for restorative care died during admission, with only a minority discharged home. Patients discharged most commonly experienced maintenance and not improvement in performance status. A successful discharge home following restorative care was associated with a shorter length of stay. Implications and recommendations for successful restorative care will be discussed.


Reference gene selection for real-time quantitative PCR analysis of the mouse uterus in the peri-implantation period.
The study of uterine gene expression patterns is valuable for understanding the biological and molecular mechanisms that occur during embryo implantation. Real-time quantitative RT-PCR (qRT-PCR) is an extremely sensitive technique that allows for the precise quantification of mRNA abundance; however, selecting stable reference genes suitable for the normalization of qRT-PCR data is required to avoid the misinterpretation of experimental results and erroneous analyses. This study employs several mouse models, including an early pregnancy, a pseudopregnancy, a delayed implantation and activation, an artificial decidualization and a hormonal treatment model; ten candidate reference genes (PPIA, RPLP0, HPRT1, GAPDH, ACTB, TBP, B2M, 18S, UBC and TUBA) that are found in uterine tissues were assessed for their suitability as internal controls for relative qRT-PCR quantification. GeNorm(PLUS), NormFinder, and BestKeeper were used to evaluate these candidate reference genes, and all of these methods identified RPLP0 and GAPDH as the most stable candidates and B2M and 18S as the least stable candidates. However, when the different models were analyzed separately, the reference genes exhibited some variation in their expression levels.


[My fingers itch, but my hands are bound. An exploratory psychosomatic study of patients with dyshidrosis of the hands (cheiropompholyx)].
The purpose of a pilot study with 20 patients, suffering from dyshidrotic exzema of the hands, was to investigate the relevance of a psychosomatic approach for its etiology and therapy. A set of psychological and allergological tests revealed the following results. - 10 patients suffered from a contact allergy (epicutaneous test), 6 of them were allergic to nickel - the patients were less aggressive and more permissive (Freiburger Personality Inventory; FPI) as compared to a standard population. They reported more somatic complaints (HHM) as healthy subjects. - the results of a semistructured interview support the hypothesis, that the dyshidrotic exzema often has an expressive function: the patients present their dependency conflict in a symbolic manner by means of their hands. They try to take their life in their own hands; autonomous actions however are hampered by their own dependency needs. The development of the dyshidrotic symptoms corresponds to the autonomy, which has been achieved with regard to the individual conflict of ambivalence. According to our findings the contact with nickel is not predominant, neither causative nor triggering, factor. Following the psychosomatic concept of Engel and Schmale, the authors discuss the pathogenesis of dyshidrosis with the meaning of a complication of (pregenital) conversion, with the hands as the part affected.


[Effect of integrin-linked kinase on the growth of prostate cancer in nude mice].
To investigate the effect of the integrin-linked kinase (ILK) small interfering RNA (siRNA) on prostate cancer in nude mice by orthotopic injection of human cell line DU145. The cultured human cell line DU145 was knocked down for ILK using a siRNA .Cellular ILK expression was quantified by RT-PCR and Western blot analysis. Moreover, cell attachment, invasiveness and microfilament dynamics assays were performed. Furthermore, the impact of the ILK siRNA on the prostate cancer was tested using a nude mice model in which prostate cancer was induced by orthotopic injection of human prostate cancer cell line DU145.Gross tumor volume of prostate in nude mice,cell differentiation,the state of apoptosis and proliferation were tested after 5 weeks of injection. The expression of ILK was suppressed significantly by siRNA, cellular mRNA and protein of ILK decreased 87% and 81% separately. The knockdown of ILK also induced the attachment and invasiveness of DU145 cell growing down. The tumor volume, cell differentiation, apoptosis index and proliferation index of prostate in nude mice of ILK siRNA orthotopic injection model were significantly smaller, better, increased and decreased separately than those in control group. Targeting inhibition of ILK not only decreases attachment and invasiveness of human DU145 cells, but also suppresses the growth and development of prostate cancer of orthotopic injection human DU145 cell line model in nude mice.


Valorization of grape (Vitis vinifera) byproducts. Antioxidant and biological properties of polyphenolic fractions differing in procyanidin composition and flavonol content.
Many byproducts and wastes generated by agroindustries contain polyphenols with potential application as food antioxidants and preventive agents against skin cancer and other diseases. The performance of polyphenolic fractions from Parellada grape (Vitis vinifera) pomace as antioxidants in different physicochemical environments was tested. Fractions containing oligomers with mean degree of polymerization between 3 and 4 and percentage galloylation ca. 30% were the most potent free radical scavengers and efficient antioxidants in an oil-in-water emulsion. A fraction including glycosylated flavonols was also efficient in the emulsion. All the fractions showed low aquatic toxicity and weak influence on proliferation of human melanoma cells.


[Correction of prominent malar complex by L-type osteotomy].
To present a new method for correction of prominent malar complex by L-shaped osteotomy through an intraoral incision. Based on the anatomical characteristics of the malar complex, we designed a new L-shaped osteotomy for malar eminence reduction. The procedure includes oblique incision of the upper part of the mala, vertical incision of the anterior part of the mala and "greenstick" fracture of the zygomatic arches. According to the severity of malar prominence, we resect part of the anterior-inferior part of the mala and lower the malar complex. This method was used in 39 patients with prominent malar complex. Of them, 32 were symmetrical and 7 were unsymmetrical. All the patients obtained good results. L-shaped osteotomy for correction of prominent malar complex is a relatively ideal surgical method with the advantages of simpler manipulation, fewer complications, better result, and ensuring the intactness of the structural characteristics of the malar complex.


Findings on the portable chest radiograph correlate with fluid balance in critically ill patients.
Fluid balance concerns occur daily in critically ill patients, complicated by difficulties assessing intravascular volume. Chest radiographs (CXRs) quantify pulmonary edema in acute lung injury (ALI) and total blood volume in normal subjects. We hypothesized that CXRs would reflect temporal changes in fluid balance in critically ill patients. Standardized scoring of 133 supine, portable, anteroposterior CXRs. Outcomes included subjective and objective measures of intravascular volume and pulmonary edema. Academic university medical center and affiliated Veterans Affairs hospital. Thirty-seven patients with ALI receiving mechanical ventilation blindly randomized to treatment with diuretics and colloids or dual placebo for 5 days. Treated patients experienced a 3.3-L diuresis and 10-kg weight loss during the 5-day period. A significant correlation was observed in all patients between changes in vascular pedicle width (VPW) and net intake/output (r = 0.50, p = 0.01) or weight (r = 0.51, p = 0.01). The correlation between VPW and fluid balance was greatest for weight changes in the treatment group alone (r = 0.71, p = 0.005). Pulmonary artery occlusion pressure correlated highly with changes in VPW (r = 0.70, p < 0.001). After day 1, CXRs revealed significant between-group differences in VPW without changes in cardiothoracic ratio or subjective measures of edema. The proportion of patients with VPW < 70 mm did not differ at baseline but was significantly more in the treatment group on all subsequent days (p < 0.05). We conclude that temporal fluid balance changes are reflected on commonly utilized portable CXRs. Objective radiographic measures of intravascular volume may be more appropriate indicators of fluid balance than subjective measures, with VPW appearing most sensitive. If systematically quantitated, serial CXRs provide a substantial supplement to other clinically available data for the purpose of fluid management in critically ill patients.


[Dynamic measurement of volume of atelectasis area in the evaluation of the prognosis of patients with moderate-to-severe acute respiratory distress syndrome].
To assess the impact of not inflated lung tissue (NILT) volume on the prognosis of patients with moderate-to-severe acute respiratory distress syndrome (ARDS). The clinical data of 131 patients with moderate-to-severe ARDS admitted to the intensive care unit (ICU) of Tianjin Third Central Hospital from March 2016 to June 2019 were collected. The basic data of patients, including gender, age, body mass index (BMI), causes of ARDS, acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score and oxygenation index (PaO2/FiO2), were collected. The CT imaging data of patients on the 1st and 7th day in the ICU were collected. According to the CT value, they were divided into hyperventilated areas (-1 000 to -900 HU), normal ventilation areas (-899 to -500 HU), poorly ventilated areas (-499 to -100 HU), and atelectasis area (-99 to 100 HU). The total lung volume and the percentage of NILT to the total lung volume (NILT%) were calculate. At the same time, duration of mechanical ventilation, length of ICU stay, total length of hospital stay were collected. According to the 28-day follow-up, they were divided into survival group and death group. Multivariate Logistic regression analysis was used to determine the risk factors for 28-day death in ARDS patients. The receiver operating characteristic (ROC) curve was drawn, the area under ROC curve (AUC) and 95% confidence interval (95%CI) were calculated to determine the accuracy of NILT% in predicting the 28-day prognosis of ARDS patients, and the NILT% threshold was used for subgroup analysis of patients. Among the 131 patients with moderate-to-severe ARDS, patients were excluded for more than 48 hours after ARDS diagnosis, repeated admission to ICU due to ARDS, the ICU duration less than 7 days, death within 72 hours of admission, chronic interstitial lung disease or congestive heart failure, no chest CT examination within 7 days of admission to ICU, and no specimen collection within 2 hours of admission to ICU. Finally, a total of 53 patients were enrolled in the analysis. Of the 53 patients, 31 patients survived and 22 patients died. The 28-day mortality was 41.5%. Compared with the survival group, patients in the death group were older (years old: 65.32±11.29 vs. 55.77±14.23), and had a higher SOFA score (11.68±3.82 vs. 8.39±2.23) with significant differences (both P < 0.05), while there were no significant differences in gender, BMI, ARDS cause, APACHE II score and PaO2/FiO2 between the two groups. There was no significant difference in CT value, total lung volume and NILT% between the two groups at 1st day after admission to ICU; NILT% on day 7 after admission to ICU in the death group was significantly higher than that in the survival group [(28.95±8.40)% vs. (20.35±5.91)%, P < 0.01], but there was no significant difference in CT value and total lung volume between the two groups. Multivariate Logistic regression analysis showed that the 28-day prognosis of ARDS was related to age, SOFA score and NILT% independently [age: odds ratio (OR) = 0.892, 95%CI was 0.808-0.984, P = 0.023; SOFA score: OR = 0.574, 95%CI was 0.387-0.852, P = 0.006; NILT%: OR = 0.841, 95%CI was 0.730-0.968, P = 0.016]. ROC curve analysis showed that 7-day NILT% could predict the 28-day prognosis of patients with moderate-to-severe ARDS, and AUC was 0.810 (95%CI was 0.678-0.952, P < 0.01). The NILT% threshold was 15.50%, sensitivity was 95.5%, specificity was 80.6%, positive predictive value was 85.7%, and negative predictive value was 74.6%. According to the 7-day NILT% threshold, a subgroup analysis of patients was performed, and 7-day NILT% > 15.50% was defined as a high-risk clinical prognosis, and ≤ 15.50% was a low-risk. Compared with low-risk patients (n = 7), the duration of mechanical ventilation, the length of ICU stay and total length of hospital stay in high-risk patients (n = 46) were significantly prolonged [duration of mechanical ventilation (days): 9.37±6.14 vs. 4.43±1.72, length of ICU stay (days): 12.11±5.85 vs. 7.57±1.13, total length of hospital stay (days): 18.39±5.87 vs. 11.29±2.22, all P < 0.05]. The 7-day NILT% > 15.50% of patients with moderate-to-severe ARDS after ICU admission is related to poor prognosis.


[Demonstration of transposition in Portulaca grandiflora (HOOK)].
The gene C of Portulaca grandiflora encodes a product required for the synthesis of flower pigment. The cmI allele gives white flowers with violet spots and sectors. It is also germinally unstable and can give rise to a series of cm alleles conferring different flower color phenotypes. These findings suggest that allele C may be rendered genetically unstable as a consequence of transposable element insertion and excision.


Severe human infections caused by Vibrio metschnikovii.
Vibrio metschnikovii is largely distributed in the aquatic environment; human infections are rarely observed. A fatal case of septicemia in a patient with liver cirrhosis, renal insufficiency, and diabetes is described. A second case in a 82-year-old woman with septicemia, respiratory problems, and infected leg lesions is reported; she was successfully treated.


Medication adherence for 90-day quantities of medication dispensed through retail and mail order pharmacies.
To examine relative medication adherence of patients filling 90-day supplies of maintenance medications using retail and mail order channels. It was hypothesized that adherence rates would not differ across the 2 channels. A cross-sectional retrospective analysis was conducted using de-identified pharmacy claims data from a large pharmacy benefit manager (PBM) database over a 2-year period (January 2008 to August 2010). Patients who were continuously eligible for at least 12 months during this time frame, with benefit plan designs that allowed filling of 90-day supplies either at retail or by mail order pharmacy, were selected. Adherence was measured by medication possession ratio (MPR) within a 1-year period. Propensity score matching was employed to minimize differences between the Retail-90 group and Mail Order-90 group. Overall, patients filling 90-day prescriptions for 9 therapeutic groups (antiasthmatics and bronchodilators, antidepressants, antidiabetics, antihyperlipidemics, antihypertensives, beta blockers, calcium channel blockers, diuretics, and thyroid agents) at retail pharmacies demonstrated a propensity score–matched average MPR that was statistically higher than for patients filling prescriptions via mail order (77.0% vs 76.0%). There were no significant differences in MPR (post-matching) between 90-day retail and mail order channels for individual therapeutic groups, except for antidiabetics (80.2% vs 83.1%). On a propensity-matched basis, patients who fill maintenance prescriptions at retail have a slightly, but statistically significantly, higher MPR than patients who fill their prescriptions by mail


Auto-transplantation in the restorative management of traumatized anterior teeth: a case report.
Auto-transplantation can be used to replace missing anterior teeth following traumatic injuries. This technique has the advantage (over other forms of treatment) of maintaining alveolar bone height which allows orthodontic and further restorative intervention by way of implants later in life. Careful restorative management of transplanted teeth is vital to their long-term survival as inadequate maintenance post transplant may result in root resorption and eventual tooth loss. This paper describes the restorative management of two cases following transplantation. Dental practitioners should be aware of the option to auto-transplant teeth as part of an overall treatment plan and the subsequent interventions often required.


[Choroidal vessels alterations in treated and untreated diabetic rats].
To evaluate the diabetic alterations and the impact of short and long-term medical treatment on them. Thirty Wistar rats were divided into 3 groups: control (GC), diabetic (DG), and treated diabetic (TG) and the observations were made 1 month (M1) and 12 months (M2) after diabetes induction. Diabetes was induced by intravenous alloxan (42 mg/kg). The treated group received acarbose orally and insulin by subcutaneous injection. Eyes were prepared for transmission electron microscopy, specifically for ultrastructure of the Bruch membrane and choroidal vessels. Ultrastructural examination of the diabetic rat choroid showed deposits in the Bruch membrane and accumulation of vesicles, glycogen and dense bodies in endothelial cell cytoplasm. The most affected group was that of the diabetics on month 12 (GDM2). The treated diabetics showed the least alterations on month 12 (GTM2). Diabetic rats develop degenerative alterations in the Bruch membrane and choroidal vessels. These alterations are more evident in animals submitted to chronic disease, but they are also present in acute disease. Degenerative processes were not avoided with short-term treatment. Long-term treatment inhibited the progress of these processes.


A New Feature Ensemble with a Multistage Classification Scheme for Breast Cancer Diagnosis.
A new and effective feature ensemble with a multistage classification is proposed to be implemented in a computer-aided diagnosis (CAD) system for breast cancer diagnosis. A publicly available mammogram image dataset collected during the Image Retrieval in Medical Applications (IRMA) project is utilized to verify the suggested feature ensemble and multistage classification. In achieving the CAD system, feature extraction is performed on the mammogram region of interest (ROI) images which are preprocessed by applying a histogram equalization followed by a nonlocal means filtering. The proposed feature ensemble is formed by concatenating the local configuration pattern-based, statistical, and frequency domain features. The classification process of these features is implemented in three cases: a one-stage study, a two-stage study, and a three-stage study. Eight well-known classifiers are used in all cases of this multistage classification scheme. Additionally, the results of the classifiers that provide the top three performances are combined via a majority voting technique to improve the recognition accuracy on both two- and three-stage studies. A maximum of 85.47%, 88.79%, and 93.52% classification accuracies are attained by the one-, two-, and three-stage studies, respectively. The proposed multistage classification scheme is more effective than the single-stage classification for breast cancer diagnosis.


Luciferase assembly after transport into mammalian microsomes involves molecular chaperones and peptidyl-prolyl cis/trans-isomerases.
The assembly of a heterodimeric luciferase was studied after de novo synthesis of corresponding precursor proteins in reticulocyte lysate and concomitant transport into dog pancreas microsomes. This cytosolic luciferase from a prokaryotic organism (Vibrio harveyi) was specifically used as a model protein to investigate (i) whether the eukaryotic cytosol and the microsomal lumen have similar folding capabilities and (ii) whether the requirements of a polypeptide for certain molecular chaperones and folding catalysts are determined by the polypeptide or the intracellular compartment. The two luciferase subunits were fused to the preprolactin signal peptide. Data indicate that efficient assembly of luciferase occurs in the mammalian microsomes. Furthermore, it was observed that luciferase assembly can be separated in time from synthesis and membrane transport, depends on ATP hydrolysis, is partially sensitive to cyclosporin A and FK506, and in the absence of lumenal proteins is less efficient as compared with the presence of lumenal proteins. Thus, heterodimeric luciferase depends on functionally related molecular chaperones and folding catalysts during its assembly in either the eukaryotic cytosol or the microsomal lumen.


Microarray analysis reveals a potential role of lncRNA expression in remote ischemic preconditioning in myocardial ischemia-reperfusion injury.
The challenge to avoid or reduce cardiopulmonary bypass-related injuries in cardiovascular surgery remains a major issue. Remote ischemic preconditioning (RIPC) remains a promising strategy whose clinical applications appear to be significantly more realistic and extensive as compared with other conservative or surgical strategies. However, considering its underlying mechanism(s) are still unclear, novel ideas and methods must be explored to enhance its potential in clinical applications. Long noncoding RNAs (LncRNAs) are a kind of RNAs that have been implicated in the occurrence and development of cardiovascular diseases. The differently expressed LncRNAs and their biological effects during RIPC have not been explored previously. In this study, mouse and human LncRNA microarrays were used to investigate the expression signatures of LncRNAs and mRNAs in the myocardial tissue after RIPC. Therafter, homology comparisons were used to screen homologous genes from differentially expressed LncRNAs. Competing endogenous RNA (ceRNA) mechanism analysis were employed to find the matching relationship among homologous LncRNA, mRNA and microRNA. 554 differentially expressed mouse LncRNAs (281 up-regulated/273 down-regulated) and 1392 differentially expresssed human LncRNAs (635 up-regulated/757 down-regulated) were selected for further analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to quantify these LncRNAs, homology comparison and ceRNA mechanism analysis provided a pair of homologous LncRNAs (ENST00000574727 & ENSMUST00000123752) for further research investigation. Overall, in this study, a number of differentially expressed LncRNAs were identified which may play an important role the regulation of both inflammation and cell proliferation. The findings may thus unveil the mystery of RIPC and discover a novel protective mechanism for the mitigation of cardiovascular ischemia-reperfusion disease.


Molecular and histologic evaluation of idiopathic hyperextension of the metacarpophalangeal and metatarsophalangeal joints in adult llamas.
To determine the molecular and histologic characteristics of hyperextension of the metacarpophalangeal and metatarsophalangeal joints in adult llamas. 12 adult llamas (6 with bilateral hyperextension of the metacarpophalangeal or metatarsophalangeal joints [affected] and 6 age- and sex-matched clinically normal control llamas). Llamas were euthanized, and specimens of superficial digital flexor tendon, deep digital flexor tendon, and suspensory ligament were obtained from 4 areas and snap frozen in liquid nitrogen or suspended in neutral-buffered 10% formalin. Histologic evaluation of collagen fiber orientation, elastin content, and proteoglycan content was performed by use of Masson trichrome, picrosirius red, Verhoeff, and Alcian blue stains. Total RNA was isolated from frozen suspensory ligament specimens. Gene expression of collagen types I and III, lysyl oxidase, and matrix metalloproteinase-13 was evaluated with a real-time quantitative reverse transcriptase PCR assay. Gene expression of collagen types I and III, lysyl oxidase, and matrix metalloproteinase-13 in suspensory ligaments was similar between affected and control llamas. Collagen orientation and elastin content of the flexor tendons and suspensory ligaments were also similar between the groups. Proteoglycan content was low in most specimens but was focally increased in discrete lesions of suspensory ligaments in 2 affected and 2 control llamas. Hyperextension of the metacarpophalangeal or metatarsophalangeal joints in llamas did not appear to be caused by degeneration or inflammation of the suspensory ligament. Although focal proteoglycan accumulation existed in the suspensory ligaments of 2 affected llamas, widespread abnormal connective tissue proteoglycan accumulation was not found.