Analysis of LSD in human body fluids by high-performance liquid chromatography, fluorescence spectroscopy and radioimmunoassay.
A scheme of analysis is described in which the particular advantages of high-performance liquid chromatography (HPLC), fluorescence spectroscopy and radioimmunoassay (RIA) are exploited to the greatest effect. RIA affords a rapid and sensitive preliminary screening method, while the subsequent HPLC analysis using fluorimetric detection yields quantitative chromatographic evidence together with characteristic fluorescence spectra. Fractionation of samples by HPLC followed by RIA of the fractions gives further confirmation of the presence of LSD and its metabolites. The combined methodology has been applied to the analysis of LSD in body fluids for forensic and clinical purposes. Levels down to 0.5 ng of LSD per ml can be detected using the minimum of sample.


Calcium, phosphorus and magnesium balance: FM 85 fortification of human milk does not meet mineral needs of extremely low birthweight infants.
Extremely low birthweight (<1000 g) infants are growing rapidly and their nutritional requirements for calcium, phosphorus, magnesium are high. Prospective, mineral balance. The study was carried out at the Department of Neonatology, Virchow-Hospital, Charité Berlin and the Department of Molecular Trace Element Research, Hahn-Meitner-Institute Berlin. Nineteen infants <1000 g birthweight were admitted, nine infants dropped out and 10 infants (birthweight 730-995 g), fed fortified human milk were included. We collected infant's urine and feces for 72 h, a sample of human milk and infant's blood at 7 and 12 weeks of age. Elements were measured by inductively coupled plasma atomic emission spectrophotometry. Mean (s.d.) mineral concentration in milk was low especially at 12 weeks: calcium 9.88 (+/-3.58) mmol/l, phosphorus 7.02 (+/-3.81) mmol/l, magnesium 1.59 (+/-0.54) mmol/l. Calcium retention was minimal or negative during the study, whereas phosphorus and magnesium balances were positive. Caffeine and diuretics increased mineral excretion. Serum alkaline phosphatase was mostly <800 U/l, and 162 U/l in one infant with zinc deficiency at 12 weeks. Alkaline phosphatase correlated with absorption and retention of phosphorus, and with longitudinal growth. Infants <1000 g have high nutritional needs for calcium, phosphorus and magnesium, which are not met by a human milk fortifier widely used in Europe. Controlled trials are needed to assess requirements, duration and risks of mineral supplementation.


Variable metabolism of pinacidil: lack of correlation with the debrisoquine and trimethylamine C- and N-oxidative polymorphisms.
1. The urinary excretion of pinacidil and its N-oxide in man was found to vary over a five-fold range. 2. Studies in individuals with inherited deficiencies for C-hydroxylation (debrisoquine type) and trimethylamine N-oxidation showed that the N-oxidation of pinacidil did not co-segregate with these oxidative polymorphisms. 3. It is concluded that the variable N-oxidation of pinacidil is most likely to be due to variations in the activity of the P-450 isozymes rather than in the microsomal flavoprotein containing mixed-function amine oxidase of Ziegler which is considered to be responsible for the N-oxidation of trimethylamine.


Plasminogen Activator Inhibitor-1-Positive Platelet-Derived Extracellular Vesicles Predicts MACE and the Proinflammatory SMC Phenotype.
Patients with established coronary artery disease remain at elevated risk of major adverse cardiac events. The goal of this study was to evaluate the utility of plasminogen activator inhibitor-1-positive platelet-derived extracellular vesicles as a biomarker for major adverse cardiac events and to explore potential underlying mechanisms. Our study suggests these extracellular vesicles as a potential biomarker to identify and a therapeutic target to ameliorate neointimal formation of high-risk patients.


Photoinhibition as a control on photosynthesis and production of Sphagnum mosses.
The effect of high light intensity on photosynthesis and growth of Sphagnum moss species from Alaskan arctic tundra was studied under field and laboratory conditions. Field experiments consisted of experimental shading of mosses at sites normally exposed to full ambient irradiance, and removal of the vascular plant canopy from above mosses in tundra water track habitats. Moss growth was then monitored in the experimental plots and in adjacent control areas for 50 days from late June to early August 1988. In shaded plots total moss growth was 2-3 times higher than that measured in control plots, while significant reductions in moss growth were found in canopy removal plots. The possibility that photoinhibition of photosynthesis might occur under high-light conditions and affect growth was studied under controlled laboratory conditions with mosses collected from the arctic study site, as well as from a temperate location in the Sierra Nevada, California. After 2 days of high-light treatment (800 μmol photons m-2 s-1) in a controlled environmental chamber, moss photosynthetic capacity was significantly lowered in both arctic and temperate samples, and did not recover during the 14-day experimental period. The observed decrease in photosynthetic capacity was correlated (r 2=0.735, P<0.001) with a decrease in the ratio of variable to maximum chlorophyll fluorescence (F v/F m) in arctic and temperate mosses. This relationship indicates photoinhibition of photosynthesis in both arctic and temperate mosses at even moderately high light intensities. It is suggested that susceptibility to photoinhibition and failure to photoacclimate to higher light intensities in Sphagnum spp. may be related to low tissue nitrogen levels in these exclusively ombrotrophic plants. Photoinhibition of photosynthesis leading to lowered annual carbon gain in Sphagnum mosses may be an important factor affecting CO2 flux at the ecosystem level, given the abundance of these plants in Alaskan tussock tundra.


Expression of disodium cromoglygate 'protective' effects observed during V79 cell proliferation.
Disodium cromoglycate (DSCG) in equimolar concentration of 0.56 mumol/l preincubated with an asynchronous cell population decreases the inhibition of proliferation and results in a 100% elimination of inhibition of colony formation induced by benfluron (BF). DSCG protects the cells from unbalanced growth and unbalanced metabolism (e.g., prevention of increase or decrease in protein cell content, glycolytic activity and in amino acid metabolism) which are both the integrating parts of BF cytotoxic reaction. The protective effect of DSCG is manifested also on synchronous cell populations, particularly in G2 phase (26%). DSCG also stabilizes cell membrane by preventing the alterations of its permeability caused by the cytolytic concentrations of benfluron (at a concentration of 1.05 mumol/l and more).


Proteome labeling and protein identification in specific tissues and at specific developmental stages in an animal.
Identifying the proteins synthesized at specific times in cells of interest in an animal will facilitate the study of cellular functions and dynamic processes. Here we introduce stochastic orthogonal recoding of translation with chemoselective modification (SORT-M) to address this challenge. SORT-M involves modifying cells to express an orthogonal aminoacyl-tRNA synthetase/tRNA pair to enable the incorporation of chemically modifiable analogs of amino acids at diverse sense codons in cells in rich media. We apply SORT-M to Drosophila melanogaster fed standard food to label and image proteins in specific tissues at precise developmental stages with diverse chemistries, including cyclopropene-tetrazine inverse electron demand Diels-Alder cycloaddition reactions. We also use SORT-M to identify proteins synthesized in germ cells of the fly ovary without dissection. SORT-M will facilitate the definition of proteins synthesized in specific sets of cells to study development, and learning and memory in flies, and may be extended to other animals.


Microfilaria causing nephrotic syndrome: Highlighting the importance of diethylcarbamazine provocation test for diagnosis.
Filarial parasite infestation not only affects the structure and function of lymphatic vessels but is also associated with extralymphatic pathology and disease. Incidence of renal involvement in microfilaria carriers has led to increased cognizance of extralymphatic presentation. Literature set forth clinical syndromes having extralymphatic manifestation of filaria. The diagnosis of filariasis is done by visualisation of microfilaria in peripheral blood smear, lymphatic tissue. Other modalities of diagnosis are Enzyme linked immunosorbent assay (ELISA), Immunochromatographic test. Diethyl carbamazine (DEC) provocation test usually is done to detect microfilaria in night blood smear due to the nocturnal periodicity of microfilaria. The drug DEC flushes the microfilaria into the peripheral circulation leading to high probability of detection. We present a case of a 59-year-old male who was diagnosed as nephrotic syndrome and after a DEC challenge we detected microfilaria in the peripheral smear confirming microfilaria-induced Nephrotic Syndrome after all other secondary conditions were excluded.


Cultivating Chlorella vulgaris and Scenedesmus quadricauda microalgae to degrade inorganic compounds and pesticides in water.
This work evaluates the possibility of cultivating Scenedesmus quadricauda and Chlorella vulgaris microalgae in wastewater from the hydroponic cultivation of tomatoes with the aim of purifying the water. S. quadricauda and C. vulgaris were also used in purification tests carried out on water contaminated by the following active ingredients: metalaxyl, pyrimethanil, fenhexamid, iprodione, and triclopyr. Fifty-six days after the inoculum was placed, a reduction was found in the concentration of nitric nitrogen, ammonia nitrogen, and soluble and total phosphorus. The decrease was 99, 83, 94, and 94 %, respectively, for C. vulgaris and 99, 5, 88, and 89 %, respectively, for S. quadricauda. When the microalgae were present, all the agrochemicals tested were removed more quickly from the water than from the sterile control (BG11). The increase in the rate of degradation was in the order metalaxyl > fenhexamid > iprodione > triclopyr > pyrimethanil. It was demonstrated that there was a real degradation of fenhexamid, metalaxyl, triclopyr, and iprodione, while in the case of pyrimethanil, the active ingredient removed from the substrate was absorbed onto the cells of the microalgae. It was also found that the agrochemicals used in the tests had no significant effect on the growth of the two microalgae. The experiment highlighted the possibility of using cultivations of C. vulgaris and S. quadricauda as purification systems for agricultural wastewater which contains eutrophic inorganic compounds such as nitrates and phosphates and also different types of pesticides.


The sequential organ failure assessment (SOFA) score is prognostically superior to the model for end-stage liver disease (MELD) and MELD variants following paracetamol (acetaminophen) overdose.
The prognostic value of the model for end-stage liver disease (MELD) and sodium-based MELD variants in predicting survival following paracetamol overdose remains unclear. To examine the prognostic accuracy of sodium-based MELD variants in paracetamol-induced acute liver injury compared with the sequential organ failure assessment (SOFA) score. Retrospective analysis of 138 single time point paracetamol overdoses admitted to a tertiary liver centre. Individual laboratory samples were correlated with the corresponding clinical parameters in relation to time post-overdose, and the daily MELD, MELD-Na, MELDNa, MESO, iMELD, UKELD, updated MELD and SOFA scores were calculated. Sixty-six (47.8%) patients developed hepatic encephalopathy, of whom 7 were transplanted and 21 died without liver transplantation. SOFA had a significantly greater area under the receiver operator characteristic for the prediction of spontaneous survival compared with MELD at both 72 (P = 0.024) and 96 (P = 0.017) h post-overdose. None of the sodium-based MELD variants improved the prognostic accuracy of MELD. A SOFA score >6 by 72 h or >7 by 96 h, post-overdose predicted death/transplantation with a negative predictive value of 96.9 (95% CI 90.2-99.4) and 98.8 (95% CI 93.6-99.9) respectively. SOFA and MELD had similar accuracy for predicting the development of hepatic encephalopathy (P = 0.493). The SOFA score is superior to MELD in predicting spontaneous survival following paracetamol-induced acute liver injury. Modification of the MELD score to include serum sodium does not improve prognostic accuracy in this setting. SOFA may have potential as a quantitative triage marker following paracetamol overdose.


Co-mitogenic tumor promoters suppress the phosphatidylinositol response in lymphocytes during early mitogenesis.
The tumor-promoting agents 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and phorbol-12,13-dibenzoate inhibited the increased accumulation of [32P]phosphatidylinositol (PI) induced in mouse spleen lymphocytes by mitogenic lectins in the presence of [32P]orthophosphate. Similar inhibition of [32P]PI levels by TPA was seen in human tonsil T-lymphocytes stimulated with phytohemagglutinin. Only co-mitogenic phorbol esters prevented the [32P]PI accumulation during early mitogenesis. No increased 32P-labelling due to mitogen or decreases due to TPA was observed when cells were equilibrated with [32P]orthophosphate for 24 h prior to stimulation with mitogen, from which it is concluded that the total concentrations of phosphatidylcholine (PC) and PI are unaffected by mitogen or co-mitogen. The [32P]PI elevation but not the [32P]PC elevation was proportional to T-cell mitogenic potency for the lectins concanavalin A, divalent succinyl concanavalin A and phytohemagglutinin, and was prevented in each case by 5 X 10(-8) M TPA. Escherichia coli lipopolysaccharide did not give increased 32P incorporation into PI or PC, and TPA had no effect on 32P labelled phospholipid levels in the presence of this B-cell mitogen. The results indicate that the phosphatidylinositol response is not an invariable correlate of T-cell mitogenesis by polyclonal mitogens.


Application and optimization of label-free shotgun approaches in the study of Quercus ilex.
Advances in proteomic equipment, algorithms and wet protocols are being increasingly reported. Each step in the experimental workflow must be adapted and optimized to the target experimental system and objectives. The influence of the amount of peptides loaded onto the column in shotgun platforms has rarely been considered to date even though it dictates the confidence with which proteins can be identified and quantified. An experiment using variable dilutions of protein equivalent mixtures of root, leaf and seed tissue extracts of Quercus ilex was performed by subjecting BSA protein equivalent amounts of 1-100 μg to SDS-PAGE, the resulting bands being trypsin digested and peptides (10-1000 ng protein equivalents) loaded onto an LC column. Mass spectra were used to identify proteins against the in-house Q. ilex transcriptome database. Determinations included SEQUEST quantification (average of the three most abundant distinct peptides for each protein) and proteotypic peptides. The number of proteins identified was found to depend on peptide load and to peak at 2054 with 600 ng. Smaller loads led to linearly decreasing identifications from 1859 with 400 ng to 495 with 10 ng. Both quantification strategies provided similar results. The linear dynamic range was from 100 to 600 ng.


Supramolecular Surface Charge Regulation in Ionic Covalent Organic Nanosheets: Reversible Exfoliation and Controlled Bacterial Growth.
Poor control on the exfoliation of covalent organic frameworks (COFs) remains a disadvantage for their application as two-dimensional nanosheets. An equally important problem is the reversible control at the available surface charges on COFs. Herein, a strategy for the reversible exfoliation, re-stacking, and surface-charge control of a propidium iodide based ionic covalent organic framework, PI-TFP, using cucurbit[7]uril (CB[7]) induced molecular recognition, is reported. The surface charge on PI-TFP facilitates its initial self-exfoliation. However, complexation with CB[7] resulted in re-stacking with concomitant decrease in zeta potential from +28±3.0 to +0.004±0.003 mV. Addition of 1-adamantylamine hydrochloride (AD) facilitates decomplexation of PI-TFP from CB[7], resulting in exfoliation and an increase in zeta potential to +24±3.0 mV. Such control on the exfoliation, re-stacking, and the associated regulation of the surface charge in PI-TFP was exploited for controlling bacterial growth. Thus, the activity of E. coli and S. aureus bacteria obtained with the self-exfoliated PI-TFP could be reversibly controlled by the CB[7]/AD pair.


[Manipulations in genetic engineering. Consequences and fields of application].
The genetic engineering permits to produce useful proteins. Authors describe some aspects of cloning strategies and the principal applications in medical, industrial and agricultural domains.


Development of Protein-Specific Analytical Methodologies to Evaluate Compatibility of Recombinant Human (rh)IGF-1/rhIGFBP-3 with Intravenous Medications Co-Administered to Neonates.
The protein complex of recombinant human insulin-like growth factor-1 and insulin‑like growth factor binding protein‑3 (rhIGF-1/rhIGFBP-3; mecasermin rinfabate), is an investigational product for the prevention of complications of prematurity. Delivery of rhIGF-1/rhIGFBP-3 is by continuous central line intravenous infusion in preterm infants until endogenous IGF-1 production begins. Protein-specific analytical methodologies were developed to evaluate the compatibility of rhIGF-1/rhIGFBP-3 at low protein concentrations (∼2.5-10 μg/mL) expected when co-administered with other required medications in the NICU. Highly sensitive detection of the biologic potential degradants (fragments) and/or molecular modifications (oxidized species, aggregates) required the use of reversed-phase high-performance liquid chromatography and size-exclusion ultra-performance liquid chromatography coupled with mass spectrometric detection. We report on the quantification of rhIGF-1/rhIGFBP-3, its components and degradants, to a limit of quantitation of 3.1 μg/mL upon mixing with 24 commonly administered neonatal medications. Methods developed for the rhIGF-1/rhIGFBP-3 admixtures, optimized in studies with furosemide, caffeine citrate and ampicillin, demonstrated good reproducibility, linearity, and limit of detection/quantitation. Using these methods, no increase in degradation of rhIGF-1/rhIGFBP-3 components and no increase in oxidation or aggregation level was observed with caffeine citrate, while admixtures of rhIGF-1/rhIGFBP-3 with ampicillin yielded lower mass recovery of rhIGF-1/rhIGFBP-3 components, which likely resulted from adduct formation. Furosemide was found to be physically incompatible with rhIGF-1/rhIGFBP-3. Our findings support the use of these methodologies for detection of protein modifications under various clinical administration conditions, and additionally supplement physical compatibility data studies of ultra-low concentrations of rhIGF-1/rhIGFBP-3 post co-administration to preterm infants with other medications (manuscript in-preparation).


Formation of biologically influenced palladium microstructures by Desulfovibrio desulfuricans and Desulfovibrio ferrophilus IS5.
A range of Desulfovibrio spp. can reduce metal ions to form metallic nanoparticles that remain attached to their surfaces. The bioreduction of palladium (Pd) has been given considerable attention due to its extensive use in areas of catalysis and electronics and other technological domains. In this study we report, for the first time, evidence for Pd(II) reduction by the highly corrosive Desulfovibrio ferrophilus IS5 strain to form surface attached Pd nanoparticles, as well as rapid formation of Pd(0) coated microbial nanowires. These filaments reached up to 8 µm in length and led to the formation of a tightly bound group of interconnected cells with enhanced ability to attach to a low carbon steel surface. Moreover, when supplied with high concentrations of Pd (≥ 100 mmol Pd(II) g-1 dry cells), both Desulfovibrio desulfuricans and D. ferrophilus IS5 formed bacteria/Pd hybrid porous microstructures comprising millions of cells. These three-dimensional structures reached up to 3 mm in diameter with a dose of 1200 mmol Pd(II) g-1 dry cells. Under suitable hydrodynamic conditions during reduction, two-dimensional nanosheets of Pd metal were formed that were up to several cm in length. Lower dosing of Pd(II) for promoting rapid synthesis of metal coated nanowires and enhanced attachment of cells onto metal surfaces could improve the efficiency of various biotechnological applications such as microbial fuel cells. Formation of biologically stimulated Pd microstructures could lead to a novel way to produce metal scaffolds or nanosheets for a wide variety of applications.


Expression of Toll-Like Receptors in peripheral blood mononuclear cells and response to cognitive-behavioral therapy in major depressive disorder.
In recent years, increased attention has been paid to the inflammatory mechanisms of major depressive disorder (MDD). The aim of the present study was to investigate pro-inflammatory pathways related to the "leaky gut" hypothesis of MDD, which is based on the putative intestinal translocation of Gram-negative bacteria and a subsequent abnormal immune response mediated by the Toll-Like Receptor-4 (TLR-4) pathway. 50 patients with first-episode MDD and 30 healthy control subjects participated in the study. Real-time quantitative PCR was used to measure TLR-4 and TLR-2 RNA from peripheral mononuclear blood cells, as well as the expression of NF-κβ, a key transcription factor of the pro-inflammatory response. TLR-4 protein expression was determined by using flow cytometry. TLR-2 served as a control molecule. Low-grade inflammation was characterized by the measurement of interleukin-6 (IL-6) and C-reactive protein (CRP). Bacterial translocation was investigated by the measurement of the 16S rRNA subunit (16S rDNA) of intestinal microbiota in the blood plasma of the participants. We performed these analyses before (t1) and after (t2) cognitive-behavioral therapy (CBT) in MDD. The healthy control subjects were also assessed two times. We found significantly elevated expressions of all three markers (TLR-4 RNA and protein, NF-κβ RNA) and 16S rDNA in MDD at t1 relative to healthy control subjects. These markers showed a significant decrease during CBT (t1>t2 in MDD). We observed no between-group differences and changes in the case of TLR-2. Greater reduction of pro-inflammatory markers during CBT was associated with more pronounced clinical improvement. IL-6 and CRP displayed a moderately elevated level in MDD and did not change during CBT. In conclusion, TLR-4 signaling is up-regulated in newly diagnosed patients with MDD, which may be related to bacterial translocation or to the presence of various damage-associated molecular patterns. Clinical improvement during psychotherapy is associated with decreased expression of pro-inflammatory markers.


Rapid progressive extramedullary plasmacytoma in the orbit.
Plasma cell tumors of the orbit are uncommon and mostly the first manifestation of a multiple myeloma (MM). Primary extramedullary plasmacytoma (EMP) of the orbit is exceedingly rare and only a few cases have been reported so far. Differentiation of an EMP from a MM is important, since 9.5 years have been reported as the mean survival of EMP, compared with a mean survival of 3 to 4 years for multiple myeloma. A 68-year-old man presented with a history of rapid progressive extramedullary plasmacytoma in the right orbit, increasing in size within a few weeks. MR imaging revealed an intraorbital mass measuring 5.2 x 4.7 x 3 cm. The earlier performed biopsy was positive for plasmacytoma of the lambda light chain type. Systemic work-up was negative for further tumor spread. Irradiation (a maximum of 80 Gy) and several chemotherapy cycles showed no effect. Exenteration with sparing of the upper and lower lid skin was performed. The residual defect was covered by a Thiersch graft. Although the orbit had been irradiated with the maximal dose, the Thiersch graft healed well. Normally, EMP is slow to increase in size. In our patient, marked growth of tumor was noted within one week. One underlying reason is the poorly differentiated, blastic morphology leading to this rapid tumor growth. However, particular molecular features, like a t(4;14), could not be demonstrated.


Maternal consumption of dairy products during pregnancy and lactation, and the development of cow's milk antibodies in the offspring.
To assess whether the maternal consumption of milk and milk products affects development of cow's milk (CM) antibodies in infants. A randomized pilot trial using food frequency questionnaires (mothers) and food records (infants). Families with a newborn infant with increased HLA-DQB1-conferred risk of type 1 diabetes and at least one first-degree relative affected by type 1 diabetes from 16 hospitals in Finland between April 1995 and November 1997. Infants randomized to receive a hydrolysed formula when breast milk was not available during their first 6-8 mo (n=112). Of these, 13 dropped out by the age of 3 mo and two were excluded due to incomplete CM antibody data. Maternal milk protein intake from cheese during pregnancy was inversely related to IgA-class antibody titres to beta-lactoglobulin (BLG) and casein (CAS) at 3 mo, and to IgA antibody titres to BLG at 6 mo. Maternal consumption of raw milk products during lactation was positively related to the development of IgA antibody titres to CAS at 6 mo, and inversely correlated to IgG antibody titres to bovine serum albumin (BSA) and IgA antibody titres to CAS at 2 y. Maternal cheese consumption was inversely related to the IgG antibody titres to CM formula and CAS and to the IgA antibody titres to CAS in early infancy. Few associations were established between maternal CM protein intake and CM protein antibody levels in the infants. The milk and milk products taken by the mother differed in their impact on the emerging CM antibody response in the offspring.


Food for folivores: nutritional explanations linking diets to population density.
Ecologists want to explain why populations of animals are not evenly distributed across landscapes and often turn to nutritional explanations. In seeking to link population attributes with food quality, they often contrast nutritionally positive traits, such as the concentration of nitrogen, against negative ones, such as fibre concentration, by using a ratio of these traits. This specific ratio has attracted attention because it sometimes correlates with the biomass of colobine primates across sites in Asia and Africa. Although empirically successful, we have identified problems with the ratio that may explain why it fails under some conditions to predict colobine biomass. First, available nitrogen, rather than total nitrogen, is nutritionally important, while the presence of tannins is the major factor reducing the availability of nitrogen in browse plant species. Second, tannin complexes inflate measures of fibre. Finally, simple ratios may be unsound statistically because they implicitly assume isometric relationships between variables. We used data on the chemical composition of plants from three continents to examine the relationships between the concentrations of nitrogen, available nitrogen, fibre and tannins in foliage and to evaluate the nitrogen to fibre ratio. Our results suggest that the ratio of the concentration of nitrogen to fibre in leaves does sometimes closely correlate with the concentration of available nitrogen. However, the ratio may give misleading results when leaves contain high concentrations of tannins. The concentration of available nitrogen, which incorporates measures of total nitrogen, dry matter digestibility and tannins, should give a better indication of the nutritional value of leaves for herbivorous mammals that can readily be extrapolated to habitats.


The еffects of low mineral content water on microbiota, metabolic, and oxidative stress parameters in patients with type 2 diabetes mellitus.
Although scientific evidence has shown that natural mineral waters have potential beneficial metabolic effects, there is still very scarce data on their influence on type 2 diabetes mellitus (T2DM). The study was designed to investigate the effects of low mineral water from the "Sneznik-1/79″ source in Serbia on microbiota, metabolic, and oxidative stress parameters in patients with T2DM. In total, 60 patients with confirmed T2DM were included in the study, and they consumed "Sneznik-1/79″ water for 28 days. To examine the positive effects of "Sneznik-1/79″ water, we compared the results before and after the four weeks of "Sneznik-1/79″ water intake. Standard biochemical analyses were carried out, such as glucose level, lipid profile, and stool tests. The blood samples were collected to evaluate the effects of "Sneznik-1/79″ water on the redox status. At the end of the monitoring period, the total cholesterol concentration significantly dropped compared to the initial value. A significant improvement in intestinal peristalsis was observed, which was reflected in the fact that after four weeks, all patients established regular, daily bowel movements. Moreover, consumption of "Sneznik-1/79″ water eliminated the appearance of dysbiosis in 50% of patients. Additionally, the antioxidant capacity was improved by increasing the concentration of superoxide dismutase and reduced glutathione. The result of our study pointed out that the intake of "Sneznik-1/79″ water could be a promising adjuvant therapy for improving intestinal peristalsis as well as reducing the appearance of dysbiosis in T2DM patients.


Influence of solvent on the growth of ZnO nanoparticles.
We have synthesized ZnO nanoparticles by precipitation from zinc acetate in a series of n-alkanols from ethanol to 1-hexanol as a function of temperature. In this system, nucleation and growth are relatively fast and, at longer times, the average particle size continues to increase due to diffusion-limited coarsening. During coarsening, the particle volume increases linearly with time, in agreement with the Lifshitz-Slyozov-Wagner (LSW) model. The coarsening rate increases with increasing temperature for all solvents and increases with alkanol chain length. We show that the rate constant for coarsening is determined by the solvent viscosity, surface energy, and the bulk solubility of ZnO in the solvent.


Gene mapping by linkage and association analysis.
Genetic analysis is used to map genes, including disease loci, to positions within the human genome. Linkage analysis depends on the co-segregation of a gene (locus) and a phenotype through a pedigree, while association analysis, or linkage disequilibrium mapping, depends on measuring deviation from the random occurrence of alleles in a haplotype in unrelated individuals or nuclear families. Complex computer programs may be used in both forms of analysis. In recent years most interest has focused on identifying genes involved in common, multifactorial diseases. Here I review some current and developing techniques of genetic analysis and give references to where further information can be obtained.


Topical Delivery of Lactobacillus Culture Supernatant Increases Survival and Wound Resolution in Traumatic Acinetobacter baumannii Infections.
Species of Lactobacillus have been proposed as potential candidates for treating wound infections due to their ability to lower pH, decrease inflammation, and release antimicrobial compounds. This study investigated the impact of lactobacilli (Lactobacillus acidophilus ATCC 4356, Lactobacillus casei ATCC 393, Lactobacillus reuteri ATCC 23272) secreted products on wound pathogens in vitro and in a murine wound infection model. Evaluation of 1-5 day lactobacilli conditioned media (CM) revealed maximal inhibition against wound pathogens using the 5-day CM. The minimum inhibitory concentration (MIC) of 5-day Lactobacillus CMs was tested by diluting CM in Mueller-Hinton (MH) broth from 0 to 25% and was found to be 12.5% for A. baumannii. Concentrating the CM to 10× with a 3 kDa centrifuge filter decreased the CM MIC to 6.25-12.5% for A. baumannii planktonic cells. Minimal impact of 5-day CMs was observed against bacterial biofilms. No toxicity was observed when these Lactobacillus CMs were injected into Galleria melonella waxworms. For the murine A. baumannii wound infection studies, improved survival was observed following topical treatment with L. acidophilus ATCC 4356 or L. reuteri ATCC 23272, while L. reuteri ATCC 23272 treatment alone improved wound resolution. Overall, this study suggests that the topical application of certain Lactobacillus species byproducts could be effective against gram-negative multi-drug resistant (MDR) wound pathogens, such as A. baumannii.


Induction of cutaneous mast cell tumors by N-methyl-N'-nitro-N-nitrosoguanidine followed by TPA in female mice of 4 out of 5 strains tested.
Appreciable yields of cutaneous mast cell tumors were induced in a two-stage skin carcinogenesis protocol comprising N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) initiation followed by 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion in 4 of 5 strains of mice. Only female mice of each of the 5 strains were studied. The incidences of benign and/or malignant lesions differed considerably between strains; 27% in DBA/2, 22% in BDF1, 11% in BALB/c, 10% in CDF1 and 0% in C57BL/6 mice and no mast cell tumors were detected in any of the strains when treated with the initiator alone. First found in a DBA/2 mouse at week 50, most tumors were observed after 100 weeks of promotion, and were usually small in size (less than 2 mm in diameter) and predominantly located within the corium, although they occasionally extended into the subcutaneous tissue. Histologically, the benign mast cell tumors were composed of non-encapsulated, well circumscribed densely packed sheets of discrete cuboidal or rhomboid cells. Metachromatic granules were clearly visible in the cytoplasm by Toluidine Blue staining. Two of the tumors induced in DBA/2 mice were diagnosed as malignant mast cell tumors on the twin bases of cellular atypia and deep infiltration into the muscular layer. The cutaneous mast cell tumors were constantly accompanied by subepidermal mast cell aggregations which were also commonly observed in tumor-free skin of mice receiving the initiation-promotion procedure.


Early experience conducting school-located vaccination programs for seasonal influenza.
We determined program effectiveness, feasibility, and acceptance of school-located vaccination (SLV) clinics for seasonal influenza that took place before the 2008 universal influenza vaccination recommendations. We surveyed program directors of 23 programs in the United States who conducted SLV clinics during the 2005 to 2006 and 2006 to 2007 influenza seasons. Of 391,423 children enrolled in schools with SLV clinics, 61,463 (15.7%) were vaccinated at 499 sites (schools) in 23 programs. Of these, 22 were small- and medium-sized programs that vaccinated 32,875 (24.1%) of the 136,151 children enrolled there, averaging 31.9% of students per site. One populous county vaccinated an additional 28,588 (11.2%) of its 255,272 enrolled children, averaging 13.9% per school. Children in grades K to 6 had consistently higher mean vaccination rates (21.5%) compared with middle school children (10.3%) or high school youth (5.8%). Program acceptability was high, and no program had to forego any key public health activities; 5 hired temporary help or paid overtime. The outlook for continuing such clinics was good in 7 programs, but depended on help with vaccine purchasing (9), funding (8), or additional personnel (4), with multiple responses allowed. These vaccination coverage rates provide a baseline for future performance of school-located mass vaccination clinics. Although the existence and conduct of these programs in our study was considered acceptable by leaders of public health departments and anecdotally by parents and school administrators, sustainability may require additional means to pay for vaccines or personnel beyond the usual available health department resources.


Water under the BAR.
Many cellular processes require the generation of highly curved regions of cell membranes by interfacial membrane proteins. A number of such proteins are now known, and several mechanisms of curvature generation have been suggested, but so far a quantitative understanding of the importance of the various potential mechanisms remains elusive. Following previous theoretical work, we consider the electrostatic attraction that underlies the scaffold mechanism of membrane bending in the context of the N-BAR domain of amphiphysin. Analysis of atomistic molecular dynamics simulations reveals considerable water between the membrane and the positively charged concave face of the BAR, even when it is tightly bound to highly curved membranes. This results in significant screening of electrostatic interactions, suggesting that electrostatic attraction is not the main driving force behind curvature sensing, supporting recent experimental work. These results also emphasize the need for care when building coarse-grained models of protein-membrane interactions. These results are emphasized by simulations of oligomerized amphiphysin N-BARs at the atomistic and coarse-grained level. In the coarse-grained simulations, we find a strong dependence of the induced curvature on the dielectric screening.


Therapeutic Vaccination against Human Papillomavirus Type 16 for the Treatment of High-Grade Anal Intraepithelial Neoplasia in HIV+ Men.
Anal cancer is increasing in HIV+ men who have sex with men (MSM). Treatment options for its precursor, high-grade anal intraepithelial neoplasia (HGAIN), are suboptimal. In this phase I to II dose-finding study, we assessed the safety and efficacy of the human papillomavirus type 16 (HPV16) synthetic long peptide vaccine (SLP-HPV-01) in HIV+ MSM with HPV16-positive HGAIN. Four dosage schedules (1-5-10; 5-10-20; 10-20-40; and 40-40-40-40 μg) of SLP-HPV-01 were administered intradermally with a 3-week interval in 10 patients per dose level (DL). In each dose group, 5 patients also received 1 μg/kg pegylated IFNα-2b subcutaneously. Primary endpoints were safety and regression of HGAIN at 3, 6, and 12 months. Eighty-one of 134 screened patients (60%) had HPV16-negative HGAIN lesions, leaving 53 eligible patients. Thirteen patients were excluded, leaving 40 men. The vaccine was well tolerated. One patient developed a generalized rash. The highest dosage level induced the strongest immune responses. There was no indication for stronger reactivity in the IFNα groups. Up to 18 months of follow-up, 8/38 intention-to-treat patients had a complete clinical and histologic response and one had a partial response (in total 9/38, 23.7%). At the highest dosage level, the clinical response was 4/10 (40%). Stronger immune responses were detected among clinical responders. The highest DL is safe, immunogenic, and associated with clinical responses to HPV16-induced lesions. However, as the majority of HGAIN is caused by the other HPV types, further studies should aim at pan-HPV vaccination to prevent or treat HGAIN.


First report of Neospora caninum infection in cattle in Sudan.
A cross-sectional survey was conducted in Sudan to determine sero-prevalence and risk factors associated with Neospora caninum infection in non-vaccinated dairy herds and to assess importance of the disease. Blood samples were collected from a total of 262 animals from 25 herds. Sera were tested for antibodies against N. caninum using ELISA test. The prevalence rates of N. caninum antibodies in cattle were high both at herd level (44%) and at individual animal level (10.7%). Herd level infection rates were similar in Khartoum State (43.7%) and at Gazira States (44.4%). The overall prevalence rates were higher (16.1%) in Gazira State than in Khartoum State (9%) but with no significant variation. The sero-prevalence at individual animal level was significantly higher (p < 0.05) in animals with history of abortion (12.8%) than in apparently healthy animal (11.3%), animal with history of infertility (8.1%), or neonatal death of calves (4.3%). In addition, significantly higher (P < 0.05) sero-prevalence was observed in samples collected during the rainy season (6.87%) than winter (3.05%) or summer (0.76%). However, no significant differences in sero-prevalence due to locality, animal breed, sex, and age were observed (p > 0.05). This preliminary study reveals for the first time the existence of natural N. caninum infection in Sudan. Also, the findings of the present study indicated that this disease is highly prevalent in two major areas of dairy production in the country, and this calls for control strategy to be implemented.


Genetic Markers as Risk Factors for the Development of Impulsive-Compulsive Behaviors in Patients with Parkinson's Disease Receiving Dopaminergic Therapy.
Impulsive-compulsive and related behavioral disorders (ICD) are drug-induced non-motor symptoms of Parkinson's disease (PD). Recently research has focused on evaluating whether ICD could be predicted and managed using a pharmacogenetic approach based on dopaminergic therapies, which are the main risk factors. The aim of our study was to evaluate the role of candidate genes such as DBH, DRD2, MAOA, BDNF, COMT, SLC6A4, SLC6A3, ACE, DRD1 gene polymorphisms in the pathogenesis of ICD in PD. We compared patients with PD and ICD (n = 49), patients with PD without ICD (n = 36) and a healthy control group (n = 365). ICD was diagnosed using the QUIP questionnaires and specific diagnostic criteria for subtypes of ICD. Genotyping was conducted using a number of PCR techniques and SNaPshot. Statistical analysis was performed using WinPepi and APSampler v3.6 software. PCA testing was conducted using RStudio software v1.4.1106-5. The following substitutions showed statistically significant correlations with PD and ICD: DBH (rs2097629, rs1611115), DRD2 (rs6275, rs12364283, rs1076560), ACE (rs4646994), DRD1 (rs686), BDNF (rs6265), these associations are novel in Russian PD patients. Our findings suggest that polymorphisms in DBH, BDNF, DRD2, ACE genes in Russian subjects are associated with an increased risk of ICD development.


Postnatal deletion of β-catenin in preosteoblasts regulates global energy metabolism through increasing bone resorption and adipose tissue fibrosis.
Many studies revealed bone can regulate global energy metabolism and our previous study also showed that Wnt/β-catenin pathway is involved in this process. To better understand the participation of canonical Wnt pathway in energy metabolism, we examined the β-catenin knock-out (β-cat KO) mice by crossing the osterix-cre transgenic mice with β-cateninflox/flox mice. First, we identified that postnatal deletion of β-catenin in preosteoblasts led to decreased fat mass and increased energy expenditure in mice. Osteoprotegerin administration largely rescued the decreased fat mass and partly normalized the energy expenditure accompanied by the inhibition of bone resorption. Anti-resorption with alendronate or RANKL-antibody could also partly rescued the decreased bone mass, decreased fat mass and increased energy expenditure in β-cat KO mice. We further found that the adipose cells in the inguinal fat tissue were smaller and the extracellular matrix components around adipocytes accumulated more in β-cat KO mice than their controls by histomorphology. Gene analysis by RT-PCR showed that the expression of collagen VI is 4.8 folds in adipose tissue of the β-cat KO mice compared with the control mice. We further detected the expression of cytokines which were related to fibrosis and the data showed that the level of TGF-beta1 was elevated in both of bone marrow serum and adipose tissue derived from the β-cat KO mice. After administration of TGF-beta1 neutralizing antibody, the impaired energy metabolism was partly rescued in β-cat KO mice. Besides, anti-resorption treatment and TGF-beta1 antibody could partly suppress the increased expression of genes related to fat tissue fibrosis. These results indicate that the abnormal global energy metabolism in β-cat KO mice may be attributed to increasing bone resorption and adipose tissue fibrosis.


Maternal Immune activity during pregnancy and socioeconomic disparities in children's self-regulation.
Maternal immune activity during pregnancy has been associated with risk for psychiatric disorders in offspring, but less is known about its implications for children's emotional and behavioral development. This study examined whether concentrations of five cytokines assayed from prenatal serum were associated with socioeconomic status (SES) and racial disparities in their offspring's self-regulation abilities. Participants included 1628 women in the Collaborative Perinatal Project (CPP). Seven behavioral items conceptually related to self-regulation were rated by CPP psychologists when children were 4 years old. Concentrations of interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, and IL-10 were assessed. Covariates included child sex and mother's age, psychiatric disorders, and medical conditions during pregnancy. There were significant SES differences in child self-regulation, with higher SES children scoring higher on self-regulation (β = 0.18, 95% CI [0.11, 0.25]), but no racial differences. The concentration of IL-8 in maternal serum was associated with higher child self-regulation, β = 0.09, 95% CI [0.02, 0.16]. In mediation analyses, variation in maternal IL-8 contributed to the association between family SES and child self-regulation (β = 0.02, 95% CI [0.003, 0.030]), explaining about one-tenth of the SES disparities. This study suggests pregnancy as an early sensitive period and maternal immune activity as an important context for child development.


Trinity mysteries: university, elite schooling and sport in Ireland.
The development of sport in Ireland was, contrary to some arguments, highly influenced by English examples and Anglo-Irish institutions. Trinity College and prestigious Irish schools did have an impact, as did the number of Irish students sent to England for public school or university education. Athleticism was evident in Ireland as it was in England. Although the development of soccer did follow a slightly different trajectory from other sports, as was also the case in both England and Scotland, this does not mean that it departed from this broad evolutionary model of Irish sport. Yet this was Ireland: and Ireland was different. As opposition to British rule intensified, forms of sporting participation took on more and more of a national symbolism. The outcome was the emergence of a very potent form of athleticism: an Irish athleticism for an Irish people.


Long-term prognosis and causes of death among survivors after out-of-hospital cardiac arrest: A population-based longitudinal study.
We aimed to identify the long-term prognosis and causes of death of out-of-hospital cardiac arrest (OHCA) survivors. Using claims data from the National Health Insurance Service (NHIS) database, we included 4937 OHCA patients (aged ≥ 18 years) who were hospitalized between January 2005 and December 2015 and had survived for 30 days or more. The endpoints were long-term mortality and causes of death. Subgroup analyses were performed based on whether cardiac procedures were performed, and risk factors associated with cardiac and noncardiac deaths were identified. We followed 4937 OHCA patients for a median of 3.3 years and up to 14 years of follow-up. The all-cause 1-, 3-, 5-, and 10-year cumulative mortality were 35.2%, 46.5%, 52.3%, and 62.7%, respectively. Regarding the 1130 OHCA survivors who had undergone cardiac procedures, the all-cause 1-, 3-, 5-, and 10-year cumulative mortality were 10.7%, 16.9%, 21.4%, and 30.6%, respectively. More patients (56.2%) died from noncardiovascular causes than from cardiovascular causes (43.8%) among the 2738 total patients who had died. The proportion of patients with cardiac death was significantly higher in the patient group with a cardiac procedure than in the group without a cardiac procedure (49.6% vs. 31.7%; P value < 0.001). A higher Charlson comorbidity index (CCI) was associated with an increased risk of cardiac mortality in the cardiac procedure group. The long-term mortality among OHCA survivors remains high, particularly within the first year. Individual characteristics are crucial for the follow-up of OHCA survivors and may help improve their long-term prognosis.


Glutathione and NADPH in plant responses to H2O2.
Modifications of cell redox state are integral to plant responses to most kinds of stresses. Intense interest has focused on the roles of oxidative stress in determining immune responses of plants to pathogenic invaders, but the interplay between oxidants such as H2O2 and antioxidants like glutathione and NADPH is still obscure. To elucidate these questions, we have used a model Arabidopsis catalase-deficient line in which increased H2O2 availability activates localized cell death and disease resistance in a salicylic acid-dependent manner. Activation of cell death and resistance by H2O2 is also dependent on glutathione status and is abolished by knocking out specific NADP-linked dehydrogenases. Thus, in addition to its antioxidant function, the NADPH-glutathione redox hub plays key signaling roles in transmitting oxidative stress signals involved in determining plant disease resistance responses.


Delivery strategies for cell-based therapies in the brain: overcoming multiple barriers.
Cell-based therapies to the brain are promising for the treatment of multiple brain disorders including neurodegeneration and cancers. In order to access the brain parenchyma, there are multiple physiological barriers that must be overcome depending on the route of delivery. Specifically, the blood-brain barrier has been a major difficulty in drug delivery for decades, and it still presents a challenge for the delivery of therapeutic cells. Other barriers, including the blood-cerebrospinal fluid barrier and lymphatic-brain barrier, are less explored, but may offer specific challenges or opportunities for therapeutic delivery. Here we discuss the barriers to the brain and the strategies currently in place to deliver cell-based therapies, including engineered T cells, dendritic cells, and stem cells, to treat diseases. With a particular focus on cancers, we also highlight the current ongoing clinical trials that use cell-based therapies to treat disease, many of which show promise at treating some of the deadliest illnesses.


Emergency valve re-replacement for embolization of prosthetic mitral valve disc during catheterization procedure.
A 47-year-old woman with a mechanical mitral valve underwent a catheter-based atrial fibrillation ablation procedure, which was complicated by the dislodgment and immediate embolization of one of the valve leaflets. Acute severe mitral regurgitation and cardiogenic shock developed, necessitating emergency reoperative mitral valve re-replacement. She subsequently underwent a successful staged retrieval of the embolized leaflet from the abdominal aorta.


The effect of extension assist orthosis with pneumatic bladders on pain and function for patients with early knee osteoarthritis.
There are few non-invasive treatment options to slow the progression of osteoarthritis (OA). Recently, a novel knee unloader brace with knee extension assist has become commercially available. Therefore, the purpose of this study was to evaluate the preliminary effectiveness of using a novel unloader brace with extension assist to improve pain and functional outcomes for patients with knee OA. Thirty subjects (17 control group, 13 brace group) completed baseline and 6-week follow up testing with no brace. Patients were randomized into a Brace or No Brace group after baseline testing. Functional tests [timed up and go (TUG), stair climbing test (SCT) and six-minute walk (6MW)], self-reported measures [Knee Outcome Survey (KOS), pain, Patient Specific Functional Scale (PSFS)] and isometric knee extension strength were assessed. Repeated measure ANOVAs were used to identify differences in group and time. Pearson correlation coefficients were calculated for both average number of steps in the brace and exercises compliance compared to change in clinical scores for each group. There was a significant interaction effect for "worst pain" (P=0.002), the brace group improved from a 7.3/10 to 4.7/10 at follow-up (P=0.006) while the control group had no change. There was an effect of time for the SCT (P=0.02), "best knee pain" (P=0.050), and knee extension range of motion (ROM) (P=0.041). There were no significant correlations between exercise compliance and change in outcomes, but when the groups were collapsed there was a significant correlation between compliance and change in knee extension ROM (r=0.526; P=0.025). The extension assist pneumatic unloader brace group demonstrated a significant and important reduction in the "worst knee pain". This may indicate that wearing the brace was able to reduce painful flares. Both groups improved over time for the SCT, "best knee pain", and knee extension ROM, which can be attributed to the stretching protocol. This unloader brace is a promising non-invasive treatment option for patients with knee OA when combined with a stretching program.


The efficacy evaluation of cryosurgery in pancreatic cancer patients with the expression of CD44v6, integrin-β1, CA199, and CEA.
Increased expression of cell adhesion molecule CD44v6, integrin-β1, carbohydrate antigen 199 (CA199), and carcinoembryonic antigen (CEA) are closely associated with the progression and metastasis of numerous cancers. In this study, peripheral blood mononuclear cell (PBMC) and serum samples were collected from 37 pancreatic cancer patients and 12 healthy people. A novel triplex TaqMan real-time reverse transcription polymerase chain reaction assay was used to measure the expression levels of CD44v6 and integrin-β1 gene in PBMCs, while chemiluminescence and enzyme-linked immunosorbent assay were used to measure the levels of CA199 and CEA expression in serum. The results showed that both the levels of CD44v6 and integrin-β1 expression had significant correlation with clinical stage, lymph node, and liver metastasis of pancreatic cancer (P < 0.05). Age, tumor size, tumor differentiation, clinical stage, lymph nodes, and liver metastasis were significantly associated with the levels of CA199 and CEA expression (P < 0.05). The levels of CD44v6, integrin-β1, CA199, and CEA expression in the patients prior cryosurgery and chemotherapy were significantly higher than those in the control group (P < 0.05), whereas no significant difference was found between the patients 1 month post cryosurgery and control group (P > 0.05). The expression levels of CD44v6, integrin-β1, CA199, and CEA in the patients 1 month post cryosurgery were significantly lower than those in the patients prior cryosurgery (P < 0.05). Interestingly, no significant difference was found for the CD44v6, integrin-β1, CA199, and CEA levels between the patients prior and post-chemotherapy (P > 0.05). The higher expression of CD44v6, integrin-β1, CA199, and CEA are closely related to the progression and metastasis of pancreatic cancer and may play a important role in the curative evaluation of cryosurgery of pancreatic cancer.


The synthesis of glycosaminoglycans in aging rat liver. A brief note.
The synthesis of glycosaminoglycans (GAG) was studied in liver slices from postnatal (9 days), young (140 days), adult (490 days) and senescent (940 days) rats. It was found that the rate of synthesis was highest in postnatal rat liver and decreased to about half in young rats with no further reduction in adult and senescent age groups. The specific radioactivity of the precursors of GAG synthesis did not change with age. The synthesis pattern of specific types of GAG in postnatal liver was characterized by a significant higher percentage of chondroitin sulfate and hyaluronic acid. In the following age classes the profile of specific GAG synthesis did not change significantly (heparin sulfate: chondroitin sulfate" hyaluronic acid: "keratin sulfate" = 84%:8.3%:1.5%:1.6%).


A Novel Soybean ERF Transcription Factor, GmERF113, Increases Resistance to Phytophthora sojae Infection in Soybean.
Phytophthora root and stem rot of soybean caused by the oomycete Phytophthora sojae, is a destructive disease worldwide. Ethylene response factors (ERFs) play important roles in regulating plant biotic and abiotic stress tolerance. In this study, a new ERF gene, GmERF113, was isolated from the highly resistant soybean 'Suinong 10.' Sequence analysis suggested that the protein encoded by GmERF113 contained a conserved AP2/ERF domain of 58 amino acid and belonged to the B-4 subgroup of the ERF subfamily. Expression of GmERF113 was significantly induced by P. sojae, ethylene, and methyl jasmonate. GmERF113 protein localized to the nucleus when transiently expressed in Arabidopsis protoplasts, could bind to the GCC-box, and acted as a transcription activator. In addition, a region of the full-length GmERF113, GmERF113-II, interacted with a basic helix-loop-helix transcription factor (GmbHLH) in yeast cells. Full-length GmERF113 also interacted with GmbHLH in planta. GmERF113-overexpressing transgenic plants in susceptible cultivar 'Dongnong 50' soybean exhibited increased resistance to P. sojae and positively regulated the expression of the pathogenesis-related genes, PR1 and PR10-1. These results indicate that GmERF113 may play a crucial role in the defense of soybean against P. sojae infection.


The relation between self-stigma and loneliness in visually impaired college students: Self-acceptance as mediator.
Loneliness, a negative emotion that is common in college students, may cause psychological disorders and behavioral issues. Particularly vulnerable are visually impaired college students, who are at an increased risk of loneliness. This study was aimed at explaining the current situation of loneliness among visually impaired college students as well as its influencing factors and exploring the intermediary role of self-acceptance between self-stigma and loneliness. Seventy-eight college students with visual impairment completed a series of self-report questionnaires, including the Self-Stigma of Disabled Scale (SSDS), the Self-Acceptance Questionnaire (SAQ), and the University of California-Los Angeles (UCLA) Loneliness Scale. Mediation analyses were conducted using PROCESS in SPSS. Participants' mean loneliness score was 44.97 ± 9.35. Two survey factors were significantly associated with loneliness: visual impairment status and relationship with parents (p < 0.05). When controlling for extent of visual damage and relationship with parents, self-stigma showed a significant predictive effect on loneliness (B = 0.37, t = 4.1023, p < 0.01). In China, visually impaired students suffer from a high level of loneliness, and self-acceptance plays a central role in connecting their self-stigma and loneliness.


Pulse NMR study of phase transitions in dipalmitoyl phosphatidylcholine multilayer systems.
Pretransition and main transition of aqueous dipalmitoyl phosphatidylcholine (DPPC) dispersions were investigated by pulse NMR. The second moment M2 inter of the proton absorption line shows significant changes at 42 degrees C and about 35 degree C. Over the whole investigated temperature range between 25 and 50 degree C a superposition of at least two distinct second moments assigned to different molecular regions was observed.


Semi-nested Taqman real-time quantitative PCR for noninvasive prenatal diagnosis of Bart's hydrops fetalis.
Non-invasive prenatal diagnosis based on detection of fetal cell-free DNA is limited when mother and father are both carriers for the same autosomal recessive mutation. Develop the semi-nested Taqman real-time PCR for quantification of alpha-thalassemia-1 SEA type deletion allele in plasma of alpha-thalassemia-1 SEA carriage pregnancies. Plasma DNA was extracted from six women who carried fetuses with normal, 11 with heterozygote alpha-thalassemia-1 SEA type deletion and seven with Bart's hydrops fetalis. DNA was amplified using conventional PCR with the primary specific primer set for alpha-thalassemia-1 SEA type deletion. PCR product was then subjected to the semi-nested real-time PCR using the secondary specific primer and Taqman probe set for alpha-thalassemia-1 SEA type deletion. The standard curve was constructed using ten-fold serial dilutions of conventional PCR product of the heterozygote alpha-thalassemia-1 SEA type deletion. Women who carried fetuses with Bart's hydrops fetalis displayed a trend toward higher mean copy number of alpha-thalassemia-1 SEA type deletion allele vs. women who carried fetuses with normal and heterozygote, albeit not reaching statistical significance. The maternally inheritedfetal allele present in maternal plasma is difficult to discern the fetal cell-free DNA from a higher background DNA of the mother Thus, further investigation is needed to improve the diagnosis ofBart's hydrops fetalis using this technique.


Tables for the selection of correct blood pressure cuff size based on self-reported height and weight and estimating equations for mid-arm circumference: data from the US National Health and Nutrition Examination Survey.
The purpose of this study was to develop practical prediction equations for estimating adult mid-arm circumference (AC) using self-reported height and weight data from NHANES III 1988-1994 and NHANES 1999-2000. Both surveys used a complex sample design to obtain nationally representative data for the US civilian noninstitutionalized population. The analytic sample consisted of 4801 men and 4854 women in NHANES III and 1960 men and 2180 women from NHANES 1999-2000. Self-reported weight, height, and age data from NHANES III were used for model building, and similar data from NHANES 1999-2000 were used for validation. An all-possible regressions procedure by gender was used to derive the mid-AC prediction equations. The final prediction equations for adult mid-AC are (for self-reported weight in pounds and height in inches) for men: AC (cm) = 32.52145 + 0.10975 x (wt)-0.26057 x (ht)-0.03028 x (age), R2 = 0.76; and for women: AC (cm) = 30.22126 + 0.13534 x (wt)-0.34121 x (ht) + 0.09014 x (age)-0.00082565 x (age2), R2 = 0.81. Based on these equations, tables were created to predict mid-AC using self-reported height and weight. Clinicians can refer to our prediction equations and reference tables to determine mid-AC and proper BP cuff sizes.


Variation in herbivore density among host plants and its consequences for community structure : Field studies on willow sawflies.
The densities of four species of gall-forming sawflies were found to vary significantly among willow host plant clones. Two of the speices varied among host plants at four sites in each of three years. The other two species varied in density among host plants at most of the sites in two of the three years. Total sawfly density also varied significantly among clones. Individual species densities on willow clones were significantly positively correlated between years when all sites were combined and frequently when sites were considered separately. Most pairwise species combinations were independent in density between years, but some negative correlations existed between the stem galler and the leaf galler. Gall-former densities also were largely independent among clones within years with all sites combined and with sites considered separately. The significant correlations were nearly all positive. At all four sites the combination of significant variation in sawfly densities among willow clones in the field and independence of species densities among clones resulted in significantly different communities (relative abundance of species) among willow clones in three years. Although sawfly abundances differed substantially among the four sites, this remained true. It is argued that the pattern of community structure among clones is the result of variation in host plant quality of clones. We propose an hypothesis to account for patterns of herbivore species associations based on intrapopulation host plant variation.


Krimighna (anthelmintic) role of Neem Oil (medicated oil of Azadirachta indica Linn.) and adjuvant Ayurvedic therapies in the management of anal myiasis: A case report.
Myiasis is an uncommon pathology of parasitic infestation in live mammals by fly larvae (maggots). The fly grows and gets nourished by invading host tissue. Epidemiology of Myiasis has been recorded in tropical regions of world. No any documentation has been found on Ayurvedic intervention for anal myiasis management. The study is about a 49-year male having anal myiasis along and interno-external piles together. The case was managed by local application of Neem oil (Medicated oil of Azadirachta indica Linn.) soaked gauze piece once a day on daily bases in the invaded tissues of myiasis along with Ksharasutra ligation in the base of pile mass once during the treatment protocol. Internal medicines like Pippali (Piper longum Linn.), Erand Bhrisht Haritaki (Terminalia chebula Retz. roasted with castor oil) and Vidanga (Embelica ribes Burm. f.) were prescribed along with the local management during the course of the treatment. The case was completely cured and was relieved in 29 days. Neem oil revealed Krimighna (anthelmintic) effect which helped in tissue debridement and enhanced wound healing. Neem oil remains less irritant on local application and also gives soothing effect and kills the maggots as well.


Preterm birth: Strategies for establishing adequate milk production and successful lactation.
Whilst human milk has not evolved to meet the unique requirements of the preterm infant there are unquestionable benefits to be gained via breast milk in terms of the development and health of the infant. Many mothers of preterm infants struggle to achieve a full milk production for many reasons the mechanisms of which are still unclear. Strategies to enhance milk volume include early, frequent simultaneous expression of milk combined with breast massage and a reduction of stress. However, these are not always successful, therefore a greater understanding of lactation physiology is required to devise more effective interventions to increase milk supply. The difficulty these infants experience transitioning to oral feeding and ultimately full breastfeeding further complicates lactation. In order to improve the health of these already compromised infants it is critical that more research be directed to this area so that they reap all the benefits that can be gained from breastfeeding.


Differential phthalocyanine photosensitization of acute myeloblastic leukaemia progenitor cells: a potential purging technique for autologous bone marrow transplantation.
The potential value of sulphonated aluminium phthalocyanine (AISPc) as a purging agent for bone marrow autografts in acute myeloblastic leukaemia (AML) has been studied using in vitro clonogenic assays for normal (GM-CFC) and leukaemic (AML-CFC) progenitor cells. In nine out of 13 cases, the leukaemic blasts were found to be highly sensitive to AISPc. In six of the sensitive cases clonogenic assays revealed that only 2 +/- 1% of AML progenitor cells survived AISPc treatment under conditions which permitted a GM-CFC recovery of 60 +/- 11%. AISPc photosensitization was also shown to selectively eliminate the leukaemic cell line K562 from an in vitro model of minimal residual disease. Thus photosensitization using AISPc may be an effective method of purging marrow autografts in some cases of AML. Evaluation of the sensitivity of AML clonogenic cells at diagnosis may identify those patients in whom AISPc photo-purging may be of benefit at the time of an autologous bone marrow transplant.


Factors associated with complications of submental intubation in 339 patients with facial fractures: A German retrospective cohort study.
For nearly four decades, submental intubation (SI) has been introduced and employed to avoid tracheostomy in facial trauma cases where nasal/oral intubation is infeasible or associated with possible risks. The purposes of this study were to estimate the frequency and to identify variables associated with complications of SI (CSI). The authors organised a retrospective cohort study and enrolled a group of patients with facial trauma and SI during a seven-year interval at two German level one trauma centres where SI has routinely been used in complex facial trauma cases. The predictor variables included demographic, medical, dental, fracture-related, operative, and postoperative parameters. The outcome variable was CSI. We used descriptive, bivariate, and multivariate analyses at the 0.05 significant level. The sample included 339 patients (24.5% females, 9.4% had complications) with an average age of 58.2 ± 12.0 years (range, 17-89). Bivariate analyses revealed nine significant variables. However, forward stepwise multiple logistic regression modelling identified three variables statistically associated with CSI: smoking (OR, 691.8; 95% CI, 75.9 to 6303.9; P < 0.0001; number needed to harm [NNH], 6), moderate to high gingival inflammation (OR, 786.7; 95% CI, 66 to 9378.9; P = 0.002; NNH, 12), and postoperative use of chlorhexidine mouthwash (OR, 0.03; 95% CI, 0.001 to 0.77; P = 0.0003; number needed to treat [NNT], 2). smokers and subjects with gingivitis were more likely to experience CSI. Postoperative chlorhexidine rinsing was the potentially modifiable, albeit low-OR, factor. These findings could help to draw an effective guideline against the CSI.


Correction: Strategies for the hypothermic preservation of cell sheets of human adipose stem cells.
[This corrects the article DOI: 10.1371/journal.pone.0222597.].


Application of zirconium-iridium permanent modifier for the simultaneous determination of lead, cadmium, arsenic, and nickel in atmospheric particulate matter by multi-element electrothermal atomic absorption spectrometry.
A novel and robust method for the simultaneous determination of lead, cadmium, arsenic, and nickel in atmospheric particulate matter by multi-element electrothermal atomic absorption spectrometry was developed, using zirconium-iridium coating as permanent modifier (140 μg Zr and 4 μg Ir). After 300 atomization cycles, it was necessary to add 2 μg of Ir. Due to the varying concentrations of Pb in atmospheric particulate matter, lead was monitored at two wavelengths, at the less sensitive line of 261.4 nm for high concentration samples (>20 μg L(-1)) or at 283.3 nm for the low concentration samples. Matrix-matched calibration had to be performed for quantitative recoveries (96-102 %). Following this approach, the four elements were determined in atmospheric particulate matter samples from an industrial area near the city of Athens in two different time periods (cold-warm) with limits of detection of 5.5 ng m(-3) for Pb at 261.4 nm and 0.29 ng m(-3) at 283.3 nm, 0.019 ng m(-3) for Cd, 0.14 ng m(-3) for As, and 0.22 ng m(-3) for Ni. Lead, Cd, and As levels were very low, whereas Ni content was at comparable levels with other areas worldwide.


Detection and grading of oesophageal varices by fibre-optic endoscopy and barium swallow with and without Buscopan.
Detection of oesophageal varices is important in the diagnosis of portal hypertension. We have, therefore, compared the results of fibre-optic endoscopy and barium swallow in 56 patients with chronic liver disease. Oesophageal varices were graded as small, moderate or gross by independent observers for each technique. In 12 patients varices were not detected by either method, and in six cases varices were detected by endoscopy when the barium swallow was negative. In 15 of the remaining 38 patients varices were found to be one grade larger at endoscopy than on barium swallow. Since it is possible that varices appear larger at endoscopy because of the Buscopan (hyoscine N-butyl bromide) used as a relaxant, we carried out barium examinations after Buscopan 20 mg i.v. in 23 of the patients. In eight cases varices were one grade larger after Buscopan than on the standard barium swallow, and in two were only detected after Buscopan had been given. Eight cases negative after Buscopan were also negative at endoscopy. Although emergency endoscopy has particular value in locating the site of bleeding in patients with portal hypertension and acute gastrointestinal haemorrhage, the results of the present study suggest that a barium meal with Buscopan is as accurate as endoscopy in the detection of oesophageal varices.


Efficient degradation-aided selection of protease inhibitors by phage display.
In this report, we describe a novel phage display strategy for the identification of dedicated protease inhibiting peptides, based on degradation-aided enrichment of protease resistant phages. Phages were directly incubated with a range of phage-degrading proteases, after which non-degraded phages were used for the next selection round. For proteinase-K we identified after only four selection rounds a peptide (VLIMPVLLGIPLLC) that inhibits proteinase-K activity with an inhibition constant of 4 microM. In analogy, we identified a peptide capable of inhibiting substrate degradation by cathepsin-S (VWNCERITISRLIN), which showed functional inhibition of cathepsin-S induced sprouting of endothelial cells. We envision that the pursued strategy of degradation-aided selection of protease inhibitors (DASPI) represents an effective approach in the design of new protease inhibitors but also of new strategies to render gene and drug vectors protease resistant.


Spectroscopic investigation of tolmetin interaction with human serum albumin.
The interaction of tolmetin (TOL) with human serum albumin (HSA) in physiological buffer solution (pH 7.4) was studied by fluorescence and UV-vis absorption spectroscopy at different temperatures, combined with time-resolved fluorescence measurements. The experimental results showed that there was a strong fluorescence quenching of HSA by tolmetin. Using the continuous variation method, a single class of binding sites for TOL on HSA was put in evidence. The binding constants Ka were calculated at different temperatures, using a nonlinear fit to the experimental data, and the thermodynamic parameters ΔH(0), ΔS(0) and ΔG(0) were given. The obtained thermodynamic signature suggests that at least van der Waals and electrostatic type interactions are present. Quenching efficiency calculations, based on steady state and time-resolved spectroscopy, indicate that both static and dynamic quenching mechanisms are present.


Determinant factors of under-five mortality in Southern Nations, Nationalities and People's region (SNNPR), Ethiopia.
Child mortality is a key indicator of the performance of the health system of a nation. Impressive progress in the reduction of under-five mortality has been made in Ethiopia. However, still there are some regions where the under-five mortality rates are high. Southern Nations, Nationalities, and Peoples' Region (SNNPR) is among those regions in Ethiopia with high under-five mortality rates. This study aimed to identify the determinant factors of under-five mortality in SNNPR. Data used for the study were drawn from the 2016 EDHS. A total of 1277 under-five children were included in the study. A multivariable logistic regression model was fitted to identify determinant factors associated with under-five mortality. Children with second or third birth order (OR = 1.316, 95% CI: (1.097, 2.343)), fourth or fifth birth order (OR = 1.934, 95% CI: (1.678, 3.822)), sixth or above birth order (OR = 3.980, 95% CI: (2.352, 6.734)) were significantly associated with increased risk of under-five mortality as compared to those with first birth order. Increased risk of under-five mortality was also significantly associated with a family size of five or more (OR = 3.397, 95% CI: (1.702, 6.782)) as compared to the family size of less than five; smaller size at birth (OR = 1.714, 95% CI: (1.120, 2.623)) as compared to larger size at birth; multiple births (OR = 1.472, 95% CI: (1.289, 2.746)) as compared to singletons. On the other hand, female children (OR = 0.552, 95% CI: (0.327, 0.932)), children born at health institutions (OR = 0.449, 95% CI: (0.228, 0.681)) and children who were breastfed (OR = 0.657, 95% CI: (0.393, 0.864)) were significantly associated with decreased risk of under-five mortality as compared to male children, those born at home and those who were not breastfed respectively. Sex of a child, birth order, size of a child at birth, place of delivery, birth type, breastfeeding status, and family size were significant factors associated with under-five mortality in SNNPR, Ethiopia. Thus, planning and implementing relevant strategies that focus on those identified determinant factors of under-five mortality is required for the improvement of child survival in SNNPR, Ethiopia.


Carcinogenic profile, toxicity and source apportionment of polycyclic aromatic hydrocarbons accumulated from urban road dust in Tokyo, Japan.
Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in urban environments. Urban road dust (URD) generated by traffic is an important PAH accumulator. Twelve priority PAHs in < 2000 µm fraction of ten URD samples from Tokyo, Japan were characterized based on profile distributions, carcinogenicity, toxicity, and source apportionment by cluster analysis, biplot and diagnostic ratios. PAH concentrations (mg/kg dry weight) in arterial roads, highways, highway parking, highway drainage pit and residential area URD samples were 2.06-4.24, 0.25-3.37, 3.44, 4.94, and 5.26 respectively, dominated by the ∑4 rings (average 46%) and ∑5 + 6 rings (average 41%) PAHs. Biplot analysis revealed that the antecedent dry weather period, vehicle frequency and organic matter content were the dominant environmental factors governing PAH profiles of different road types. The total amount of carcinogenic PAHs in the residential URD (2.12 mg/kg) was higher than those in the arterial road (0.60-2.00 mg/kg) and highway (0.10-1.84 mg/kg) URD. Toxic equivalent concentrations (TECs) of residential, arterial road and highway URD were 0.54, (0.12-0.57), and (0.02-0.51) mg/kg, respectively. The dominant PAH sources were found to be petrogenic combustion in arterial road and highway URD, and pyrogenic combustion consisting of a mix of biomass, petroleum and traffic-related sources in the residential and highway drainage pit samples. This is also the first study to find that TEC-based toxicity should not be taken as a measure of URD toxicity.


Longitudinally consistent estimates of intrinsic functional networks.
Increasing numbers of neuroimaging studies are acquiring data to examine changes in brain architecture by investigating intrinsic functional networks (IFN) from longitudinal resting-state functional MRI (rs-fMRI). At the subject level, these IFNs are determined by cross-sectional procedures, which neglect intra-subject dependencies and result in suboptimal estimates of the networks. Here, a novel longitudinal approach simultaneously extracts subject-specific IFNs across multiple visits by explicitly modeling functional brain development as an essential context for seeking change. On data generated by an innovative simulation based on real rs-fMRI, the method was more accurate in estimating subject-specific IFNs than cross-sectional approaches. Furthermore, only group-analysis based on longitudinally consistent estimates identified significant developmental effects within IFNs of 246 adolescents from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) study. The findings were confirmed by the cross-sectional estimates when the corresponding group analysis was confined to the developmental effects. Those effects also converged with current concepts of neurodevelopment.


[Sensitivity test to chemotherapeutic agents and cytotoxicic test against immuno-effecter cells of established malignant fibrous histiocytoma cell line].
A cell line was established from a patient with malignant fibrous histiocytoma, which had originated in the maxillary sinus. Using this cell line, sensitivity to chemotherapeutic agents and cytotoxicity against various immunoeffecter cells were tested. This MFH cell line was sensitive in some degree to adriamycin, 5-fluorouracil, cisplatin, peplomycin, and methotrexate at high doses, but insensitive to mitomycin-C, vincristine and cyclophosphamide. Furthermore, this cell line showed no sensitivity to cytolytic cytokines, such as tumor necrosis factor-alpha and interferon-gamma. Lymphokine activated killer (LAK) cells and lymphokine activated tumor infiltrating lymphocytes (LA-TIL), induced by culture of peripheral blood lymphocytes and TIL respectively with rIL-2 showed high NK and LK activities and remarkable anti-autologous tumor ability.


A comparison of high vs standard tidal volumes in ventilator weaning for individuals with sub-acute spinal cord injuries: a site-specific randomized clinical trial.
Prospective, randomized, controlled parallel group trial with single-blinded data analysis. To determine the safety and efficacy of higher (20 ml kg(-1) ideal body weight (IBW)) vs standard (10 ml kg(-1) IBW) tidal volumes (Vt) for patients with sub-acute traumatic tetraplegia during ventilator weaning using a 14-day (minimum) weaning protocol. United States regional spinal cord injury treatment center. Thirty-three ventilator requiring inpatients were randomized to either the higher (Group 1) or the standard (Group 2) Vt protocol. Initially, all patients were ventilated at 10 ml kg(-1) IBW Vt and 5 cm H(2)O [corrected] of PEEP for 72 h. For Group 1, Vt was raised 100 ml kg(-1) until reaching target Vt of 20 ml kg(-1) IBW. Group 2 was maintained at Vt of 10 ml kg(-1) IBW. Plateau pressures were kept at or below 30 cm H(2)O. [corrected]. Safety outcomes included incidence of adverse events. Because of smaller than expected enrollment, evaluation of efficacy was not possible. Therefore, we report the safety outcomes of 33 study participants. The 16 patients in Group 1 and 17 patients in Group 2 were demographically similar at baseline, except for age. The average age was 39.3 years in Group 1 and 27.2 years in Group 2, (P=0.002). There was no difference in median days to wean: 14.5 days in Group 1 and 14 days in Group 2. The incidence of adverse pulmonary events was similar between groups. Higher tidal volumes can be safely utilized during weaning of patients with tetraplegia from mechanical ventilation using a 14-day weaning protocol.


Impact of soil movement on carbon sequestration in agricultural ecosystems.
Recent modeling studies indicate that soil erosion and terrestrial sedimentation may establish ecosystem disequilibria that promote carbon (C) sequestration within the biosphere. Movement of upland eroded soil into wetland systems with high net primary productivity may represent the greatest increase in storage capacity potential for C sequestration. The capacity of wetland systems to capture sediments and build up areas of deposition has been documented as well as the ability of these ecosystems to store substantial amounts of C. The purpose of our work was to assess rates of sediment deposition and C storage in a wetland site adjacent to a small first-order stream that drains an agricultural area. The soils of the wetland site consist of a histosol buried by sediments from the agricultural area. Samples of deposited sediments in the riparian zone were collected in 5 cm increments and the concentration of 137Cs was used to determine the 1964 and 1954 deposition layers. Agricultural activity in the watershed has caused increased sediment deposition to the wetland. The recent upland sediment is highly enriched in organic matter indicating that large amounts of organic C have been sequestered within this zone of sediment deposition. Rates of sequestration are much higher than rates that have occurred over the pre-modern history of the wetland. These data indicate the increased sedimentation rates in the wetland ecosystem are associated with increased C sequestration rates.


Non-muscular factors in upper airway patency in the rabbit.
The hypothesis tested in these experiments was that factors other than contraction of upper airway muscles influence the resistance of the upper airway to collapse. The intra-luminal pressures required to close and re-open the upper airway were measured in the isolated upper airways of anesthetised rabbits. The level of activity in upper airway muscles manipulated by ventilation with 100% O2 or 7% CO2 and by muscle paralysis with gallamine. During ventilation with 100% O2 closing pressure was -10.34 +/- 0.53 cm H2O (mean +/- 95% c.i., n = 23) and re-opening pressure was -3.15 +/- 0.51 cm H2O. Ventilation with 7% CO2 changed the closing pressure to -11.63 +/- 0.67 cm H2O (P less than 0.05) and re-opening pressure to -3.81 +/- 0.67 cm H2O (NS). In 10 animals muscle paralysis with gallamine (2 mg/kg i.v.) did not significantly alter closing or re-opening pressures during ventilation with 100% O2, and did not abolish the ability of ventilation with 7% CO2 to augment collapse resistance. In 6 animals death was followed by a fall in closing and re-opening pressures to 30-60% of the values recorded in paralysed animals. We conclude that in this preparation active muscle contraction is not the main source of resistance to airway closure or of the proclivity of the closed airway to re-open.


Temperature-dependent dual-mode thermal management device with net zero energy for year-round energy saving.
Reducing needs for heating and cooling from fossil energy is one of the biggest challenges, which demand accounts for almost half of global energy consumption, consequently resulting in complicated climatic and environmental issues. Herein, we demonstrate a high-performance, intelligently auto-switched and zero-energy dual-mode radiative thermal management device. By perceiving temperature to spontaneously modulate electromagnetic characteristics itself, the device achieves ~859.8 W m-2 of average heating power (∼91% of solar-thermal conversion efficiency) in cold and ~126.0 W m-2 of average cooling power in hot, without any external energy consumption during the whole process. Such a scalable, cost-effective device could realize two-way temperature control around comfortable temperature zone of human living. A practical demonstration shows that the temperature fluctuation is reduced by ~21 K, compared with copper plate. Numerical prediction indicates that this real zero-energy dual-mode thermal management device has a huge potential for year-round energy saving around the world and provides a feasible solution to realize the goal of Net Zero Carbon 2050.


Finite element analysis of slow drug release through deformed coating film: effects of morphology and average thickness of coating film.
This paper, a continuation of our previous work, is a presentation of the effect of the morphology and the average thickness of the deformed coating films on the slow diffusional release characteristics analyzed numerically under the constraints of the constant volume of the drug matrices and the coating films, if the films have the same average thickness. Increasing the average thickness of the coating films slows down the fractional release and the average release rate of the drug and smoothen the initial burst of the drug, as well as increase the initial lag time. The effect due to deformation of the coating films on these diffusional release characteristics are found to be less significant with the increasing average thickness of the coating films. Interestingly initial lag times are found to be the same for the coated particles having the same smallest thickness but different average thickness of coating films. The effect due to the change in the average thickness of the coating films on the characteristics of the slow controlled-release is discussed to shed light on the design of a better controlled-release device.


Quantitation of HIV-1 viral RNA in blood plasma and genital secretions.
Quantitation of HIV RNA in blood is commonly used to monitor progression of the disease and to assess the effect of antiretroviral therapy in individuals. Although not approved in the US for diagnosis of HIV infection, the finding of a positive HIV RNA with a negative HIV enzyme immunoassay and Western blot (or evolving Western blot) is an indication of primary HIV infection and should be followed up closely. Large clinical trials and cohort studies have demonstrated the importance of HIV RNA as an indicator of drug efficacy and as a factor in HIV transmission. Sexual intercourse is the most common method of transmission of HIV-1. Several studies have demonstrated that blood plasma viral load is significantly correlated with the risk of sexual HIV transmission. Additional investigations have found a significant correlation between the viral load in blood plasma and in the genital tract. This chapter describes methods of collection, processing, and testing in blood, plasma, and male and female genital secretions for quantifying HIV RNA.


The psoriasis area and severity index is an independent risk factor for cardiovascular events: A prospective register study.
Patients treated with systemics for moderate-to-severe psoriasis have increased risk of cardiovascular disease (CVD). However, to the best of our knowledge, there are no data on the association between clinical disease activity and future cardiovascular events in this population. Such data could help identify patients at increased CVD risk and inform the potential for CVD prevention with effective psoriasis treatment. To estimate the association between the Psoriasis Area and Severity Index (PASI) and cardiovascular events defined as hospitalization for CVD and cardiovascular death. We linked prospectively collected data on PASI and CVD risk factors to population-based administrative data on hospitalizations and causes of death. We estimated the association between PASI and cardiovascular events using Cox proportional hazard models with PASI and Framingham 10-year cardiovascular risk as time-varying covariates. A total of 767 patients with 6264 PASI scores were included. After adjusting for 10-year cardiovascular risk and prior CVD, a one-point increase in PASI was associated with a hazard ratio of 1.04 (95% CI: 1.01-1.07) for cardiovascular events. The findings were robust in sensitivity analyses. PASI is an independent marker for future cardiovascular events in patients with moderate-to-severe psoriasis.


Effects of Different Ammonia Concentrations on Pulmonary Microbial Flora, Lung Tissue Mucosal Morphology, Inflammatory Cytokines, and Neurotransmitters of Broilers.
Atmospheric ammonia is one of the main environmental stressors affecting the performance of broilers. Previous studies demonstrated that high levels of ammonia altered pulmonary microbiota and induced inflammation. Research into the lung-brain axis has been increasing in recent years. However, the molecular mechanisms in pulmonary microbiota altered by ambient ammonia exposure on broilers and the relationship between microflora, inflammation, and neurotransmitters are still unknown. In this study, a total of 264 Arbor Acres commercial meal broilers (21 days old) were divided into 4 treatment groups (0, 15, 25, and 35 ppm group) with 6 replicates of 11 chickens for 21 days. At 7 and 21 D during the trial period, the lung tissue microflora was evaluated by 16S rDNA sequencing, and the content of cytokines (IL-1β, IL-6, and IL-10) and norepinephrine (NE), 5-hydroxytryptamine (5-HT) in lung tissue were measured. Correlation analysis was established among lung tissue microflora diversity, inflammatory cytokines, and neurotransmitters. Results showed that the broilers were not influenced after exposure to 15 ppm ammonia, while underexposure of 25 and 35 ppm ammonia resulted in significant effects on pulmonary microflora, inflammatory cytokines, and neurotransmitters. After exposure to ammonia for 7 and 21 days, both increased the proportion of Proteobacteria phylum and the contents of IL-1β and decreased the content of 5-HT. After exposure to ammonia for 7 days, the increase in Proteobacteria in lung tissue was accompanied by a decrease in 5-HT and an increase in IL-1β. In conclusion, the microflora disturbance caused by the increase in Proteobacteria in lung tissue may be the main cause of the changes in inflammatory cytokines (IL-1β) and neurotransmitters (5-HT), and the damage caused by ammonia to broiler lungs may be mediated by the lung-brain axis.


Evaluating new simplified assays for harm reduction from methanol poisoning using chromotropic acid kits: An analytical study on Indian and Iranian alcoholic beverages.
Ingestion of methanol can result in severe irreversible morbidity, and death. Simple and easy methods to detect methanol and other hazardous additives prior to consumption can prevent fatalities. This form of harm reduction is analogous to the widely practiced "pill testing" of recreational drugs in various countries. We aimed to evaluate the performance of two qualitative and quantitative kits to simultaneously identify the presence of methanol and formaldehyde in alcoholic beverages, and compare this to the standard gas chromatographic (GC) method. Two-hundred samples of Indian and Iranian alcoholic drinks were examined by two new qualitative and quantitative chemical kits designed based on a modified chromotropic acid (CA) method, as well as a gold standard GC method. Methanol levels were similar when evaluated by GC and quantitative method (Z = - 0.328, p = 0.743). The 75th percentile of methanol level detection was 4,290 mg L-1 (range; 0-83,132) using GC compared to that of 4,671 mg L-1 (range; 0-84,960) using the qualitative kit (predefined color intensity reflecting the methanol/ethanol ratio). The quantitative kit was able to detect all methanol-contaminated and non-contaminated samples (110 and 60 cases, respectively: 100% sensitivity). In 25 samples, GC analysis showed no methanol; but the qualitative kit detected possible toxic substances. Formaldehyde measurement by UV/Vis analysis showed the presence of formaldehyde in 23 samples (92%) with a median 912 [IQR 249, 2,109; range 112-2,742] mg L-1. Methanol and formaldehyde can be easily detected using these simple CA chemical kits. Qualitative positive results may indicate the risk of poisoning if the beverage is consumed. CA kits can be used in community setting by public health units and community organizations to monitor for methanol contamination and inform a public health response to reduce methanol-related harms to the public.


Assessing the interplay between human mobility and mosquito borne diseases in urban environments.
Urbanization drives the epidemiology of infectious diseases to many threats and new challenges. In this research, we study the interplay between human mobility and dengue outbreaks in the complex urban environment of the city-state of Singapore. We integrate both stylized and mobile phone data-driven mobility patterns in an agent-based transmission model in which humans and mosquitoes are represented as agents that go through the epidemic states of dengue. We monitor with numerical simulations the system-level response to the epidemic by comparing our results with the observed cases reported during the 2013 and 2014 outbreaks. Our results show that human mobility is a major factor in the spread of vector-borne diseases such as dengue even on the short scale corresponding to intra-city distances. We finally discuss the advantages and the limits of mobile phone data and potential alternatives for assessing valuable mobility patterns for modeling vector-borne diseases outbreaks in cities.


Mitochondrial stress induces hepatic stellate cell activation in response to the ATF4/TRIB3 pathway stimulation.
The activation of hepatic stellate cells (HSCs) is the key step in the pathogenesis of liver fibrosis, which directly leads to fibrotic pathological changes in the hepatic tissue. Mitochondrial stress exacerbates inflammatory diseases by inducing pathogenic shifts in normal cells. However, the role of mitochondrial stress in HSC activation remains to be elucidated. METHODS: We analyzed the effect of mitochondrial stress on HSC activation. An in vivo hepatic fibrosis model was established by intraperitoneal injection of 40% carbon tetrachloride (CCl4) for 12 weeks. Additionally, using in vitro approach, HSC-T6 cells were treated with 10 ng/mL platelet-derived growth factor-BB (PDGF-BB) for 24 h. Transcriptional activator 4 (ATF4) is highly expressed in fibrotic liver tissue samples and activated HSCs. We found that AAV8-shRNA-Atf4 alleviated liver fibrosis in rats. ATF4 promoted the activation of HSCs, which was induced by mitochondrial stress. The mechanisms involved ATF4 binding to a specific region of the tribble homologue 3 (TRIB3) promoter. Further, TRIB3 promoted HSCs activation mediated by mitochondrial stress. ATF4 induces mitochondrial stress by upregulating TRIB3, leading to the activation of HSCs. Therefore, the inhibition of ATF4 during mitochondrial stress may be a promising therapeutic target for liver fibrosis.