Environmental spillover of emerging viruses: Is it true?
The concept of environmental "spillover" of pathogens to humans is widely used in the scientific literature about emerging diseases with the idea that it is scientifically proven. However, the exact characterization of the mechanism of spillover is simply lacking. A systematic review retrieved 688 articles using this term. The systematic analysis revealed an irreducible polysemy covering ten different definitions. It also demonstrated the absence of explicit definition in most of the articles, and even antinomies. A modeling analysis of the various processes described by these ten definitions showed that none of them corresponded to the complete trajectory leading to the emergence of a disease. There is no article demonstrating a mechanism of spillover. There are only ten articles proposing ideas on how a putative spillover could work but they merely are intellectual constructions. All other articles only reuse the term with no demonstration. It is essential to understand that since there is no scientific concept behind the "spillover", it might be dangerous to base public health and public protection against future pandemics on it.


The binding of glucose and nucleotides to hexokinase from Saccharomyces cerevisiae.
The binding of glucose, ADP and AdoPP[NH]P, to the native PII dimer and PII monomer and the proteolytically-modified SII monomer of hexokinase (ATP:D-hexose 6-phosphotransferase, EC 18.104.22.168) from Saccharomyces cerevisiae was monitored at pH 6.7 by the concomitant quenching of protein fluorescence. The data were analysed in terms of Qmax, the maximal quenching of fluorescence at saturating concentrations of ligand, and [L]0.5, the concentration of ligand at half-maximal quenching. No changes in fluorescence were observed with free enzyme and nucleotide alone. In the presence of saturating levels of glucose, Qmax induced by nucleotide was between 2 and 7%, and [L]0.5 was between 0.12 and 0.56 mM, depending on the nucleotide and enzyme species. Qmax induced by glucose alone was between 22 and 25%, while [L]0.5 was approx. 0.4 mM for either of the monomeric hexokinase forms and 3.4 for PII dimer. In the presence of 6 mM ADP or 2 mM AdoPP[NH]P, Qmax for glucose was increased by up to 4% and [L]0.5 was diminished 3-fold for hexokinase PII monomer, 6-fold for SII monomer, and 15-fold for PII dimer. The results are interpreted in terms of nucleotide-induced conformational change of hexokinase in the presence of glucose and synergistic binding interactions between glucose and nucleotide.


Effect of low-molecular-weight heparin on survival in patients with advanced pancreatic adenocarcinoma.
This retrospective analysis aimed to identify whether low-molecular-weight heparins (LMWH) might improve survival in patients receiving chemotherapeutic treatment for advanced pancreatic adenocarcinoma. Two hundred forty-three patients who had received chemotherapy for advanced pancreatic adenocarcinoma were identified from a prospectively maintained database. Of these, 30 patients had to be excluded from analysis due to insufficient documentation. Of the remaining 213 patients 94 patients had been treated with LMWH, whereas 119 patients served as controls. Outcome was assessed in relation to overall survival, which was calculated from the date of initiation of chemotherapy to the date of death. There was no significant difference (hazard ratio, 0.8; 95% confidence interval (CI), 0.6 to 1.1; P = 0,2) between the two groups in terms of overall survival. The median survival was 7.1 months (95% CI, 5.8-8.4 months) in the LMWH group and 5.9 months (95% CI, 5.1-6.7 months) in the non-LMWH group. A positive effect of LMWH was seen in patients with metastatic disease (hazard ratio for LMWH vs. non-LMWH, 0,6; 95% CI, 0,4 to 0,8; P = 0,006) in contrast to those without metastatic disease (hazard ratio for LMWH vs. non-LMWH, 1; 95% CI, 0.6 to 1.7; P = 0,96). The median survival of patients with metastatic disease was 6,6 months (95% CI, 5-8, 2 months) and 3.8 months (95% CI, 2.5-5.1 months) for the LMWH group and the non-LMWH group, respectively. In conclusion, we found for metastatic pancreatic adenocarcinoma a survival advantage for patients receiving LMWH. Nevertheless, our observations need confirmation by prospective randomized studies.


High intrinsic water use efficiency is underpinned by high stomatal aperture and guard cell potassium flux in C3 and C4 grasses grown at glacial CO2 and low light.
We compared how stomatal morphology and physiology control intrinsic leaf water use efficiency (iWUE) in two C3 and six C4 grasses grown at ambient (400 µmol mol-1) or glacial CO2 (180 µmol mol-1) and high (1000 µmol m-2 s-1) or low light intensity (200 µmol m-2 s-1). C4 grasses tended to have higher iWUE and CO2 assimilation rates, and lower stomatal conductance (gs), operational stomatal aperture (aop), and guard cell K+ influx rate relative to C3 grasses, while stomatal size (SS) and stomatal density (SD) did not vary according to the photosynthetic type. Overall, iWUE and gs depended most on aop and density of open stomata. In turn, aop correlated with K+ influx, stomatal opening speed on transition to high light, and SS. Species with higher SD had smaller and faster-opening stomata. Although C4 grasses operated with lower gs and aop at ambient CO2, they showed a greater potential to open stomata relative to maximal stomatal conductance (gmax), indicating heightened stomatal sensitivity and control. We uncovered promising links between aop, gs, iWUE, and K+ influx among C4 grasses, and differential K+ influx responses of C4 guard cells to low light, revealing molecular targets for improving iWUE in C4 crops.


Eosinophil-derived interferon-γ drives transmembrane protein 119-induced new bone formation in chronic rhinosinusitis with nasal polyps.
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory sinonasal disease characterized by eosinophilic infiltration and new bone formation. These changes indicate the severity and prognosis of CRSwNP and may be closely linked to each other. We performed RNA sequencing to screen specific osteogenic molecules and validated transmembrane protein 119 (TMEM119) expression by quantitative polymerase chain reaction (qPCR) and immunohistochemistry analyses. TMEM119 knockdown was performed to observe the downregulation of bone mineralization. We validated the bone-forming activity of interferon-γ (IFN-γ) and its signaling pathways in cultured primary sinus bone cells. Cellular sources of IFN-γ were identified using immunohistochemistry and immunofluorescence analyses. Interleukin-4-eosinophil-IFN-γ axis and the effect of dupilumab were investigated in Eol-1 cells. We observed elevated IFN-γ levels and eosinophils in the nasal fluid and predominantly eosinophil-derived IFN-γ in the sinus mucosa of patients with CRSwNP. TMEM119 expression and bone-forming activities were increased in the osteitic and primary sinus bone cells of CRSwNP. IFN-γ treatment enhanced bone mineralization and TMEM119 expression via signal transducer and activator of transcription 1 (STAT1) signaling. Moreover, TMEM119 knockdown inhibited sinus bone cell mineralization and dupilumab attenuated IFN-γ secretion by IL4-stimulated Eol-1 cells. Eosinophil-derived IFN-γ promotes the bone-forming activities of sinus bone cells via the STAT1-TMEM119 signaling pathway. Interleukin-4-eosinophil-IFN-γ axis may be crucial for TMEM119-mediated new bone formation in CRSwNP.


Voice outcome according to surgical extent of transoral laser microsurgery for T1 glottic carcinoma.
To evaluate the outcomes of transoral laser microsurgery (TLM) for T1 glottic carcinoma using longitudinal voice analysis. Retrospective analysis of medical records. We conducted a retrospective review of 57 patients (50 T1a, seven T1b) who underwent TLM for T1 glottic carcinoma, and longitudinal voice analysis was performed before surgery, during the early postoperative period (within 3 months), and during the late postoperative period (more than 6 months). Acoustic, perceptual (Grade, Roughness, Breathiness, Asthenia, Strain scale), and subjective voice analysis using the Voice Handicap Index (VHI) was conducted. Voice quality deteriorated in the early postoperative period in terms of several parameters. However, no significant differences in voice quality were observed in the late postoperative period, whereas Grade (from 1.85 ± 0.83 to 1.50 ± 0.90) and Roughness (from 1.74 ± 0.73 to 1.48 ± 0.87) had improved significantly. Patients who underwent lesser-extent cordectomy (type I, II) showed improvement in VHI-Physical (from 12.93 ± 11.10 to 6.07 ± 8.69) and Grade (from 1.60 ± 0.68 to 0.98 ± 0.83), whereas improvement was not identified in those who underwent larger-extent cordectomy (type III, IV, V). Improvement in Grade (from 1.70 ± 0.80 to 1.23 ± 0.91) and Roughness (from 1.77 ± 0.73 to 1.25 ± 0.76) was identified in patients who had unilateral tumor without involvement of anterior commissure. However, those with involvement of the anterior commissure or bilateral vocal cord showed a tendency toward deterioration in voice quality. Voice quality of patients following TLM for T1 glottic carcinoma may improve significantly over time in cases with lesser-extent types of cordectomy or unilateral tumor without involvement of the anterior commissure. 4 Laryngoscope, 126:2051-2056, 2016.


Analysis of autophagy deficiency and cytotoxicity in autophagy-deficient human embryonic stem cell-derived neurons.
Autophagy, a catabolic process governing cellular and energy homeostasis, is essential for cell survival and human health. Here, we present a protocol for generating autophagy-deficient (ATG5-/-) human neurons from human embryonic stem cell (hESC)-derived neural precursors. We describe steps for analyzing loss of autophagy by immunoblotting. We then detail analysis of cell death by luminescence-based cytotoxicity assay and fluorescence-based TUNEL staining. This hESC-based experimental platform provides a genetic knockout model for undertaking autophagy studies relevant to human biology. For complete details on the use and execution of this protocol, please refer to Sun et al. (2023).1.


l-Galactose replaces l-fucose in the pectic polysaccharide rhamnogalacturonan II synthesized by the l-fucose-deficient mur1 Arabidopsis mutant.
Arabidopsis thaliana mur1 is a dwarf mutant with altered cell-wall properties, in which l-fucose is partially replaced by l-galactose in the xyloglucan and glycoproteins. We found that the mur1 mutation also affects the primary structure of the pectic polysaccharide rhamnogalacturonan II (RG-II). In mur1 RG-II a non-reducing terminal 2- O-methyl l-galactosyl residue and a 3,4-linked l-galactosyl residue replace the non-reducing terminal 2- O-methyl l-fucosyl residue and the 3,4-linked l-fucosyl residue, respectively, that are present in wild-type RG-II. Furthermore, we found that a terminal non-reducing l-galactosyl residue, rather than the previously reported d-galactosyl residue, is present on the 2- O-methyl xylose-containing side chain of RG-II in both wild type and mur1 plants. Approximately 95% of the RG-II from wild type and mur1 plants is solubilized as a high-molecular-weight (>100 kDa) complex, by treating walls with aqueous potassium phosphate. The molecular mass of RG-II in this complex was reduced to 5-10 kDa by treatment with endopolygalacturonase, providing additional evidence that RG-II is covalently linked to homogalacturonan. The results of this study provide additional information on the structure of RG-II and the role of this pectic polysaccharide in the plant cell wall.


Co-translational protein aggregation after transient cerebral ischemia.
Transient cerebral ischemia leads to irreversible translational inhibition which has been considered as a hallmark of delayed neuronal death after ischemia. This study utilized a rat transient cerebral ischemia model to investigate whether irreversible translational inhibition is due to abnormal aggregation of translational complex, i.e. the ribosomes and their associated nascent polypeptides, initiation factors, translational chaperones and degradation enzymes after ischemia. Translational complex aggregation was studied by electron microscopy, as well as by biochemical analyses. A duration of 15 or 20 min of cerebral ischemia induced severe translational complex aggregation starting from 30 min of reperfusion and lasting until the onset of delayed neuronal death at 48 h of reperfusion. Under electron microscopy, most rosette-shaped polyribosomes were relatively evenly distributed in the cytoplasm of sham-operated control neurons. After ischemia, most ribosomes were clumped into large abnormal aggregates in neurons destined to die. Translational complex components consisting of small ribosomal subunit protein 6, large subunit protein 28, eukaryotic initiation factor-3eta, co-translational chaperone heat shock cognate protein 70 and co-chaperone HSP40-Hdj1, as well as co-translational ubiquitin ligase c-terminus of hsp70-interacting protein were all irreversibly clumped into large abnormal protein aggregates after ischemia. Translational components were also highly ubiquitinated. To our knowledge, irreversible aggregation of translational components has not been reported after brain ischemia. This study clearly indicates that ischemia damages co-translational chaperone and degradation machinery, resulting in irreversible destruction of protein synthesis machinery by protein aggregation after ischemia.


Ingested marihuana-filled balloons.
Three cases of ingestion of balloons containing marihuana are reported. In 2 patients, balloons caused intestinal obstruction. In another patient, there were symptoms of drug overdose when the contents of the balloon spilled into the intestinal tract. Pure marihuana in the gastrointestinal tract has not been reported to cause death by intoxication; however, it may be mixed with more potent substances, especially cocaine. The ingested drug or drugs should be identified as soon as possible to avoid lethal intoxication if a balloon ruptures. A balloon containing drugs will usually pass spontaneously through an uncompromised gastrointestinal tract. Nonoperative management seems appropriate if the substance has been determined to be only marihuana.


Ligand-dependent inequivalence of the α and β subunits of ferric human hemoglobin bound to haptoglobin.
Haptoglobin (Hp) prevents extra-erythrocytic hemoglobin- (Hb-)mediated damage. Hp binds αβ dimers of Hb, displaying heme-based reactivity. Here, kinetics and thermodynamics of cyanide, thiocyanate and imidazole binding to ferric human Hb (Hb(III)), Hb(III) dimers complexed with the human Hp phenotypes 1-1 and 2-2 (Hp1-1:Hb(III) and Hp2-2:Hb(III), respectively), and α(III) and β(III) chains are reported and analyzed in parallel with fluoride and azide binding properties (at pH 7.0 and 20.0 °C). Cyanide and fluoride bind to Hb(III), Hp1-1:Hb(III), Hp2-2:Hb(III), α(III), and β(III) with a simple behavior. In contrast, azide, thiocyanate and imidazole binding to Hb(III), Hp1-1:Hb(III) and Hp2-2:Hb(III) follows a two-step process, whereas ligand binding to α(III) and β(III) chains follows a simple behavior. However, azide, thiocyanate and imidazole binding to Hb(III), Hp1-1:Hb(III) and Hp2-2:Hb(III) is characterized by a simple equilibrium, reflecting the compensation of kinetic parameters. The fast and the slow step of azide, thiocyanate and imidazole binding to Hb(III), Hp1-1:Hb(III) and Hp2-2:Hb(III) mirror the ligand binding properties of the β(III) and α(III) chains, respectively. Values of kinetic and thermodynamic parameters for binding of ferric ligands to Hp1-1:Hb(III) and Hp2-2:Hb(III) match very well with those obtained for ligation of Hb(III) and α(III) and β(III) chains, confirming the ligand-dependent kinetic inequivalence of α(III) and β(III) subunits. However, a variation between tetrameric Hb(III) on one side and Hp1-1:Hb(III), Hp2-2:Hb(III), α(III), and β(III) on the other side for the rate-limiting step (likely referable to the dissociation of heme-coordinated H2O from the heme-Fe(III) atom) suggests a structural change(s) upon dimers to tetramer assembly in Hb(III).


Longterm results after phacovitrectomy and foldable intraocular lens implantation.
This study aimed to evaluate the longterm results of phacovitrectomy and foldable intraocular lens (IOL) implantation in eyes with significant cataract and co-existing vitreoretinal diseases. We carried out a retrospective study of 186 eyes of 149 patients with various vitreoretinal abnormalities and visually significant cataracts. Vitreoretinal surgery was combined with phacoemulsification and foldable IOL implantation. Main outcome measures were visual acuity (VA), preoperative data, and intraoperative and postoperative complications. The most common indications for surgery were non-diabetic vitreous haemorrhage and proliferative diabetic retinopathy. Preoperative vision ranged from 0.6 to light perception; postoperative vision ranged from 1.2 to no light perception. Postoperatively, in 162 eyes (87.1%) VA improved by >or= 3 lines on the decimal chart. In 14 eyes (7.5%), vision remained within 3 lines of preoperative levels and in 10 eyes (5.3%), vision had decreased by the last follow-up. Postoperative complications included elevated intraocular pressure and posterior capsule opacification, corneal edema, macular edema, fibrinous reaction, vitreous hemorrhage, corneal epithelial defects, anterior chamber hyphema, choroidal detachment, persistent macular hole, posterior synechiae, recurrent retinal detachment, rubeosis iridis, neovascular glaucoma. Combined vitreoretinal surgery and phacoemulsification with foldable IOL implantation is safe and effective in treating vitreoretinal abnormalities co-existing with cataract. Based on extensive experience with the combined procedure, we suggest that combined surgery is recommended in selected patients with simultaneous vitreoretinal pathological changes and cataract.


Dead bacterial biomass-assimilating bacterial populations in compost revealed by high-sensitivity stable isotope probing.
Pathogens are known to survive in compost and to regrow under the influence of certain factors, such as moisture content, temperature and nutrient availability. Dead biomass, by providing available nutrients, is a factor that may affect pathogen regrowth. However, the indigenous microorganisms, including pathogens, that grown on the dead biomass of compost have not yet been identified. Here, the regrowth potential of the pathogenic indicator bacterium Escherichia coli in the presence of dead bacterial biomass was determined, and the biomass metabolizers that grew competitively with E. coli were identified by high-sensitivity stable isotope probing of rRNA. Culture-dependent analysis indicated that the addition of dead bacterial biomass did not stimulate E. coli growth. High-throughput analysis of density-resolved 16S rRNA molecules from compost samples amended with carbon-13-labeled dead bacterial biomass revealed dead bacterial-assimilating bacteria, including Sphingobium sp., myxobacterial lineages and Bacillales. These bacteria are potentially competitive with pathogens due to their preferential assimilation of dead biomass in compost.


Aquatic photolysis of ketoprofen generates products with photosensitizing activity and toxicity.
Ketoprofen (KTF) is a nonsteroidal anti-inflammatory drug frequently detected in natural and engineering waters. Because KTF is particularly photolabile (half-life ∼4 min), knowledge of the fate and ecological risks of KTF photoproducts in the aquatic environment is especially essential. Herein, we systematically investigated the photophysics, photochemistry, and photosensitization of KTF photoproducts in aqueous solution under 365 nm irradiation (UV365). Results show that KTF photolyzed rapidly and formed 3-ethyl-α-hydroxylbenzophenone (EtOH-BP), 3-ethyl-α-hydroperoxylbenzophenone (EtOOH-BP), 3-acetylbenzophenone (AcBP), and 3-ethylbenzophenone (EtBP), as identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and high-resolution mass spectrometry (HRMS). The presence of O2 significantly affected the evolution of photoproducts during KTF photolysis. The photophysical properties of EtBP and AcBP were characterized by spectroscopic approaches. In particular, transient absorption spectra obtained by nanosecond laser flash photolysis (LFP) indicated that EtBP and AcBP were excited to triplet states with lifetimes of 28 and 2.4 µs, respectively. EtBP underwent further photodegradation, giving rise to EtOH-BP, EtOOH-BP, and AcBP upon UV365 irradiation. The reaction is proposed to proceed through an excimer precursor (3[EtBP···EtBP]*) followed by intramolecular H-abstraction. In contrast, AcBP was relatively photostable, particularly under aerated condition. Both EtBP and AcBP have strong photosensitizing activity, as evidenced by the triplet probe 4-(N,N-dimethylamino)benzonitrile (DMABN). ECOSAR program suggested that the photoproducts are more ecotoxic and bioaccumulative than the parent KTF. Results of this study underscore the need to scrutinize the formation and fate of KTF photoproducts in sunlit surface waters.


Optimization of the measurement procedure during multiphoton tomography of human skin in vivo.
The in vivo multiphoton tomography has evolved into a useful tool for the non-invasive investigation of morphological and biophysical characteristics of human skin. Until now, changes of skin have been evaluated mainly by clinical and histological techniques. The current study addresses the effects of a changed acquisition time for single scans in a Z-stack on the directly related qualitative and quantitative interpretability of the data. A test area of the skin was used for scanning 12 Z-stacks of 10 volunteers aged between 25 and 34 years. The stacks were taken up to a depth of 220 μm at increments of 10 μm at four different times, 1, 3, 7, 13 s, per scan. Subsequently, the second harmonic generation (SHG)-to-autofluorescence aging index of dermis (SAAID) was evaluated at three different measuring depths, i.e. at the maximum of SHG as well as at depths of 60 and 150 μm. The evaluation did not reveal any significant differences in the SAAID behavior between the Z-stacks of each test area scanned at different acquisition times. However, the acquisition time of 1 s/frame increases the measurement stability without influencing the SAAID behavior. The resolution of subcellular structures decreases significantly at scan times ≤3 s, whereas the acquisition time from 7 to 13 s warrants a high image quality. The study has shown that there are no significant differences between the scan speeds per scan in a Z-stack and the resulting SAAID. Acquisition times of 7 s are suitable for the morphological evaluation whereas a further extension to 13 s does not result in any benefits. A scan time per image of 1 s is sufficient for the quantitative evaluation of SAAID thus substantially reducing the possible influence of movement artifacts.


Bleeding tendency in dual antiplatelet therapy with aspirin/clopidogrel: rescue of the template bleeding time in a single-center prospective study.
Patients with heightened platelet reactivity in response to antiplatelet agents are at an increased risk of recurrent ischemic events. However, there is a lack of diagnostic criteria for increased response to combined aspirin/clopidogrel therapy. The challenge is to identify patients at risk of bleeding. This study sought to characterize bleeding tendency in patients treated with aspirin and clopidogrel. In a single-center prospective study, 100 patients under long-term aspirin/clopidogrel treatment, the effect of therapy was assayed by template bleeding time (BT) and the inhibition of platelet aggregation (IPA) by light transmission aggregometry (LTA). Arachidonic acid (0.625 mmol/L) and adenosine diphosphate (ADP; 2, 4, and 8 μmol/L) were used as platelet agonists. Bleeding episodes (28 nuisance, 2 hematuria [1 severe], 1 severe proctorrhagia, 1 severe epistaxis) were significantly more frequent in patients with longer BT. Template BT ≥ 24 min was associated with bleeding episodes (28 of 32). Risk of bleeding increased 17.4% for each 1 min increase in BT. Correlation was found between BT and IPAmax in response to ADP 2 μmol/L but not to ADP 4 or 8 μmol/L. In patients treated with dual aspirin/clopidogrel therapy, nuisance and internal bleeding were significantly associated with template BT and with IPAmax in response to ADP 2 μmol/L but not in response to ADP 4 μmol/L or 8 μmol/L.


Time to reflect on surgery and neuro-intervention for intracranial atherosclerotic diseases.
In view of the early results and halt of recruitment from both the Carotid Occlusion Surgery Study (COSS) and Stenting and the Aggressive Medical Therapy for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) study we should seize this opportunity to reflect on future directions, rather than abandoning these procedures, during this period of disillusionment. We here suggest the reasons for the failure of these two clinical trials and review future directions for researche in cerebral revascularization.


Analytical and preparative enantioseparation and main chiroptical properties of Iridium(III) bis(4,6-difluorophenylpyridinato)picolinato.
Almost all Iridium(III) complexes employed both as dopants in PhOLEDs and as pharmaceuticals and fluorescence bioprobes are racemic mixtures. In this study the single enantiomers of the most stable diastereomeric form fac-trans-N-N, bis[2-(4,6-difluorophenyl)pyridinato-C2,N](picolinato)iridium(III) (FIrpic) were separated and analysed. The data obtained showed that the complex can be separated into stable optically active Λ and Δ isomers employing cellulose based chiral stationary phase both in normal and polar phase mode. Their chirality was confirmed and their absolute configuration assigned employing several methods (DFT and TDDFT calculations, CD and VCD). The CPL spectroscopy of the isolated enantiomers of FIrpic was also recorded due to its possible value in the OLEDs field. The chromatographic method was applied for a semipreparative purpose demonstrating that polar organic solvent chromatography (POSC) could be used to avoid the low-solubility issues associated with these Iridium(III) complexes. Finally, the chemical and stereochemical stability of the single isomers was evaluated under thermal stress by liquid chromatography coupled to high-resolution mass spectrometry (LC-QTOF) on both chiral and achiral columns. No racemization and/or isomerization was observed; however, the dissociation of the ancillary ligand was demonstrated employing LC-QTOF.


The structural effect between the output module and chromophore-binding domain is a two-way street via the hairpin extension.
Signal transduction typically starts with either ligand binding or cofactor activation, eventually affecting biological activities in the cell. In red light-sensing phytochromes, isomerization of the bilin chromophore results in regulation of the activity of diverse output modules. During this process, several structural elements and chemical events influence signal propagation. In our study, we have studied the full-length bacteriophytochrome from Deinococcus radiodurans as well as a previously generated optogenetic tool where the native histidine kinase output module has been replaced with an adenylate cyclase. We show that the composition of the output module influences the stability of the hairpin extension. The hairpin, often referred as the PHY tongue, is one of the central structural elements for signal transduction. It extends from a distinct domain establishing close contacts with the chromophore binding site. If the coupling between these interactions is disrupted, the dynamic range of the enzymatic regulation is reduced. Our study highlights the complex conformational properties of the hairpin extension as a bidirectional link between the chromophore-binding site and the output module, as well as functional properties of diverse output modules.


Clinical accuracy of the Omron M3 Comfort® and the Omron Evolv® for self-blood pressure measurements in pregnancy and pre-eclampsia - validation according to the Universal Standard Protocol.
Electronic devices for blood pressure (BP) measurements need to go through independent clinical validation as recommended by different authorities, both in general and in special populations such as pregnancy. To evaluate the accuracy of the Omron Evolv® (HEM-7600T-E) and the Omron M3 Comfort® (HEM-7134-E) devices in pregnancy and pre-eclampsia according to the Universal Standard Validation Protocol. Both devices, the Evolv and the M3 Comfort, measure BP at the brachial level using the oscillometric method. The study was performed according to the recently published protocol, the so-called "modified Advancement of Medical Instrumentation (AAMI)/British Hypertension Society (BHS)/European Society of Hypertension (ESH) protocol" or the "Universal Standard Protocol." Validation of each device included 45 pregnant women in the second and third gestational trimester of whom 15 had pre-eclampsia, 15 had gestational hypertension and 15 were normotensives. BP differences between the observer and the device BP values were classified into three categories (≤5, ≤10, and ≤15 mmHg) and the mean BP differences (test vs reference) and its SD were calculated. Both devices, the Evolv and the M3 Comfort, achieved a grade A/A in both pregnancy and pre-eclampsia. The mean difference (SD) between the mercury standard and the device BP values in pregnancy were: 1) for the Evolv of -0.7±2.3 mmHg for systolic blood pressure (SBP) and -0.1±1.8 mmHg for diastolic blood pressure (DBP); 2) for the M3 Comfort of -1.6±2.8 mmHg for SBP and -0.1±2.3 mmHg for DBP. Both devices, the Evolv and the M3 Comfort, achieved a grade A/A for both SBP and DBP and fulfill the validation protocol criteria in pregnancy and pre-eclampsia. Consequently, these two devices can be recommended for home BP measurements in this specific population.


Role of echocardiography in patients with stroke.
Investigation of potential embolic source is an important diagnostic step in treating patients with ischemic stroke and transient ischemic attack. Cardiogenic embolism has been estimated to be the causative factor in 15-30% of all cases of ischemic stroke. Cardioembolic strokes are generally severe and recurrence and mortality rate high. Various cardiac disorders including atrial fibrillation, ventricular thrombus, valvular heart disease, cardiac tumors, and structural heart defects can cause cardioembolic stroke. Although the aortic arch is not a cardiac structure, it is usually considered under source of cardiac embolism (cardioaortic source) and is reviewed in this article. Echocardiography (both transthoracic and transesophageal) is a widely used and versatile technique that can provide comprehensive information of thromboembolic risk in patients with stroke. This article reviews potential cardiac sources of stroke and discusses the role of echocardiography in clinical practice.


Feline Lymphoma: Patient Characteristics and Response Outcome of the COP-Protocol in Cats with Malignant Lymphoma in The Netherlands.
Feline lymphoma is currently less commonly associated with retrovirus infections as the feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV). This is thought to have caused a shift in the distribution of anatomical subtypes and eventually have led to poorer treatment outcomes. The aim of this study was to evaluate whether this change was also notable in the Netherlands, a country historically known for its low prevalence of FeLV and FIV, and to determine its consequences on treatment response. A 10-year cohort of 174 cats with large cell lymphoma (110 treated) were included and compared to historical data from previously published reports in the Netherlands. Of the 90 cats screened, only one tested positive for FeLV and three for FIV. The most current cohort had an increased age (median 8.7 years) and fever Siamese cats (6.3%) compared to previous reports, with alimentary (24.5%) and nasopharyngeal lymphoma (22.7%) being the most common subtypes. Sixty-six of the one hundred and ten cats (60%) went into complete remission, (CR) resulting in a median disease-free period (DFP) of 763 days, with nasopharyngeal and mediastinal having the longest DFP. The median overall survival time was 274 days with an estimated 1-year survival of 41.3% and a 2-year survival of 34.6%, respectively. Patient characteristics of cats with malignant lymphoma in the Netherlands have changed over the years, but this cannot be explained by differences in FeLV/FIV prevalence. Although the overall response rate to therapy did not change over time, for some lymphoma subtypes, longer DFPs were observed compared to 30 years ago.


Adult dyskinetic cerebral palsy: Upper limb movement and muscle function.
The aim of this study was to characterize upper limb motor function during a comparative analysis of electromyographic and upper limb movement analysis during drinking between healthy adults and individuals with DCP. Fifteen healthy individuals (CG) and fifteen individuals with DCP (DG) participated in the study. Upper limb function was analyzed during drinking and consisted of a task divided into three phases: the going, the adjustment, and the return. Electromyographic analysis revealed a lower activity of the anterior deltoid, posterior deltoid, and biceps brachii muscles in the DG. When comparing the interactions between groups and phases, only biceps brachii shower lower muscle activity during going and adjustment phases. The DG presented a smaller range of motion (ROM) for the shoulder, elbow, forearm and wrist movements. An interaction between groups and phases showed smaller ROM for the flexion and internal rotation of the shoulder, elbow flexion, forearm pronation, and ulnar deviation in the return phase compared to CG. The results may contribute positively to the quantification of the level of motor impairment and may be used as a reference for the development of therapeutic interventions for patients with DCP.


The use of mucoadhesive polymers in buccal drug delivery.
Buccal delivery of the desired drug using mucoadhesive polymers has been the subject of interest since the early 1980s. Advantages associated with buccal drug delivery have rendered this route of administration useful for a variety of drugs. This review highlights the use of mucoadhesive polymers in buccal drug delivery. Starting with a review of the oral mucosa, mechanism of drug permeation, and characteristics of the desired polymers, this article then proceeds to cover the theories behind the adhesion of bioadhesive polymers to the mucosal epithelium. Additionally, we focus on the new generation of mucoadhesive polymers such as thiolated polymers, followed by the recent mucoadhesive formulations for buccal drug delivery.


Natural occurrence of deoxynivalenol, 3-acetyl-deoxynivalenol, 15-acetyl-deoxynivalenol, nivalenol, 4,7-dideoxynivalenol, and zearalenone in polish wheat.
Three wheat samples collected in 1987 in Central Poland and naturally infected withFusarium spp were analyzed for the presence ofFusarium spp andFusarium toxins. Heads were separated into three fractions: kernels with visibleFusarium damage, healthy looking kernels, and chaff + rachis.The samples contained deoxynivalenol (2.0 - 40.0μg/g), nivalenol (O.O1μg/g), 4,7-dideoxynivalenol (0.10 - 0.15μg/g). 15-acetyldeoxynivalenol (0.10-2.00 μg/g), 3-acetyldeoxynivalenol (O/1Oμg/g), and zearalenone (0.01-2.00μg/g).This is the first report about 15 - acetyldeoxynivalenol in European wheat and the co-occurrence of 3 - acetyldeoxynivalenol and 15-acetyldeoxynivalenol in the same sample of contaminated cereals.


Instrumented implants in orthopaedics.
This brief paper discusses the need for instrumentation in orthopaedic implants, and examines areas for further research and development. It is suggested that the future of this technology may have major clinical applications.


Correction: Research into the thermal stability and mechanical properties of vitamin E diffusion modified irradiation cross-linked graphene oxide/ultra-high molecular weight polyethylene composites.
[This corrects the article DOI: 10.1039/C9RA09893C.].


Heavy metal contamination in soils of a decommissioned landfill southern Brazil: Ecological and health risk assessment.
The incorrect disposal of waste negatively influences the population's quality of life and harms the environment. In Brazil, waste disposal in the open air is still a reality, which generates concerns about the contamination of the areas surrounding these dumpsites. The present work evaluated the possible environmental risks of a deactivated dumpsite in southern Brazil. The soil was characterized by physical and chemical tests, emphasizing the analysis of heavy metals Al, Fe, Cu, Mn, and Zn. Using geostatistical tools, it was possible to determine the distribution of these heavy metals in the influence of the landfill, since the metals Mn, Fe, and Zn showed a significant difference about the reference soil, indicating that they came from leaching from the landfill. The dispersion of the metals along the slope showed a tendency towards mobility since the highest concentrations were at elevations below the landfill. The area was considered contaminated due to the high scores of the evaluated indexes pollution, as the Improved Nemerow Pollution Index, which considers pollutant concentration, toxicity, and environmental impact to provide a measure of contamination, and was equivalent to 6.44, indicating that the area is contaminated. However, it presented low ecological risks, with a potential ecological risk of 18.55. As well as low risks to human health, with hazard index below the limit considered critical to health (HI < 1). Thus, the results of this study showed that the metals are released around the deactivated deposit, which compromises the environmental safety of the site, mainly due to its proximity to bodies of water that supply the region. Thus, the permanent control and monitoring of the areas of deactivated dumpsites are essential to avoid further pollution and should be included in the management plans for deactivating these deposits throughout the country.


Noroviral P particle: structure, function and applications in virus-host interaction.
Noroviruses are an important cause of epidemic acute gastroenteritis and the viruses recognize human histo-blood group antigens (HBGAs) as receptors. The protruding (P) domain of noroviral capsid, the receptor-binding domain, forms subviral particles in vitro that retain the receptor-binding function. In this study we characterized the structure and HBGA-binding function of the P particle. Structure reconstruction using cryo-EM showed that the P particles are comprised of 12 P dimers that are organized in octahedral symmetry. The dimeric packing of the proteins in the P particles is similar to that in the norovirus capsid, in which the P2 subdomain with the receptor-binding interface is located at the outermost surface of the P particle. The P particles are immunogenic and reveal similar antigenic and HBGA-binding profiles with their parental virus-like particle, further confirming the shared surface structures between the two types of particles. The P particles are easily produced in E. coli and yeast and are stable, which are potentially useful for a broad application including vaccine development against noroviruses.


Early childhood education: a means to earlier diagnosis of hearing impairment in the multihandicapped.
Detection of congenital or infantile hearing loss is often delayed in otherwise normal children, but even greater delays occur in the multihandicapped. Neonatal hearing screening and high risk register techniques have not had universal acceptance. A collaborative project between medical school otology and audiology personnel and a school for multihandicapped children under the age of 3 years in the Department of Special Education in another university has significantly reduced detection time and provided speech, language and other remedial therapy while otologic diagnosis and educational functional assessment proceed. The investigators and staff are bilingual. Parents learn to observe and work with their own child at the school and in the home.


Blunt injury to the pancreas in children: selective management based on ultrasound.
Twenty-one children with blunt injuries to the pancreas were treated over a 5-year period. Group I consisted of 12 patients brought to our hospital within 24 hours of injury. Group II included nine patients who were referred to us more than 24 hours after injury following initial treatment at another hospital. Two group I patients died within four hours of admission from other causes. Three had early laparotomy for other injuries. Of these, two had a contusion and one had a complete transection of the pancreas. All recovered uneventfully after appropriate surgical treatment. The remaining seven were all treated nonoperatively. Two had obstructive pancreatitis secondary to duodenal hematomas, three had pancreatic contusions, and two developed pancreatic pseudocysts. All seven recovered completely without operation. In group II, three patients had undergone laparotomy elsewhere. All three had pancreatic contusions. However, only one had appropriate drainage of the injured pancreas; he recovered uneventfully. Two, who were not drained, developed pseudocysts and one of these required surgical drainage by cystgastrostomy. The other six patients in group II presented to our hospital with established pseudocysts. Three of these resolved with nonoperative treatment but three required drainage. Overall, six of ten posttraumatic pancreatic pseudocysts resolved without surgical treatment. The single most useful diagnostic test in the management of these patients was abdominal ultrasound (US). US revealed specific anatomic lesions of the pancreas--contusion, obstructive pancreatitis, or pseudocyst--and provided an objective guide to management. Surgical intervention is not necessary in all cases of pancreatic trauma.


Endoparasitic flies, pollen-collection by bumblebees and a potential host-parasite conflict.
Conopid flies (Conopidae, Diptera) are common larval parasites of bumblebees. The larva develops inside the abdomen of workers, queens and males. Development is completed within 10-12 days after oviposition when the host is killed and the parasite pupates in situ. Development results in parasitised bees becoming unable to carry large loads of nectar, as the conopid larvae reside where the honey crop is normally located. Furthermore, an addition to the bee's unloaden body mass is likely (average larval weight reached at pupation by the common parasite species Sicus ferrugineus: ±SD 36.3±12.3 mg, n=59; by Physocephala rufipes: 55.8±16.9 mg, n=108). We here asked whether the propensity of workers of the bumblebee Bombus pascuorum to collect nectar rather than pollen is related to the presence of conopid larvae. For samples of bees (n=2254 workers) collected over 3 years of field studies in northwestern Switzerland, there was no difference in the frequency of bees caught as pollen collectors among parasitised (38.1% of cases, n=210) as compared to non-parastised bees (43.9%, n=360) (χ 2=1.83, n.s.). However, compared to the non-parasitised bees (n=360), those hosts containing a third (last) instar larva (n=9) were less likely to collect pollen than expected by chance χ 2=6.91, P=0.003. Similarly, hosts with short survival time between capture and being killed by the developing larva (which hence must have harboured a late instar parasite at time of capture) were less likely to collect pollen (8%, n=25) than those found not parasitised (37.6%, n=891 χ 2=9.16, P<0.001). Late instar larvae grow so big that they fill the entire abdomen. Although there was also a tendency for presumably older bees to collect less pollen, this is unlikely to explain the observations. We also discuss whether these changes in foraging behaviour of bumblebees may reflect a host-parasite conflict over the type of resource to be collected.


Prognosis of nonoperative treatment in elderly patients with a hip fracture: A systematic review and meta-analysis.
Hip fractures in frail elderly patients are associated with significant mortality and morbidity. Surgery remains the predominant treatment of choice, despite the poor prognosis. Limited research has been done with regards to nonoperative management of frail elderly patients with a hip fracture and therefore the natural course is relatively unknown. This systematic review aimed to provide an overview of the prognosis of nonoperative management in frail elderly patients with a hip fracture in terms of mortality, complications, mobility, and quality of life (QoL). A systematic review of the literature was conducted in PubMed, EMBASE, and Cochrane Central. In addition, a meta-analysis was performed. The primary outcome measurement was 30-days mortality. A total of 4,318 studies were screened. In total eighteen studies matched the eligibility criteria; with low to moderate quality. Approximately two-thirds of the patients were managed nonoperatively due to medical reasons and one-third due to non-medical reasons. Pooled mortality rates after 30 days, six months and one year were 36%, 46%, and 60%, respectively. 33% of the patients developed in-hospital complications. At six months post trauma, 9.6% of the patients were able to mobilize. Data on quality of life (QoL), functional outcome, pain, comfort during nursing care, and costs were not reported. Nonoperative management of frail elderly patients with a hip fracture is associated with a poor prognosis. Heterogenous study cohorts and limited outcomes were reported. Current literature shows a lack of evidence of the true prognosis of nonoperative management of frail elderly patient with a hip fracture and a limited life expectancy. Results of this review can be used to aid decision making and improve expectation management.


Local bone turnover in the metaphysis of the proximal tibia and the lumbar vertebra during the early periods after ovariectomy in rats.
To clarify the local changes in bone formation and resorption during the early period after ovariectomy (OVX), 200 SD rats, 4 months of age, underwent OVX or sham surgeries and seven to nine rats from each group were terminated at 1, 3, 7, 11, 15, 19, 23, 28, 35, 63, and 91 days postsurgery after tetracycline labeling. Serum intact osteocalcin levels were measured. Undecalcified sections of the 5th lumbar body (L5) and the right proximal tibia were measured for trabecular bone area, the labeled perimeters and the interlabeling distances after Villanueva's staining. On the 4th lumbar body (L4) and the left proximal tibia, undecalcified sections were measured for the trabecular osteoclast by tartrate-resistant acid phosphatase staining. The uterine horns were atrophied on the 3rd postovariectomy day (day 3). Serum osteocalcin levels increased on day 7 and reached the highest value on day 23. In either L5 or the metaphysis of the proximal tibia, trabecular bone volume (BV/TV) significantly decreased on day 15. The trabecular bone loss on day 28 was approximately 50% in the tibia and 15% in the L5. In either the lumbar or the tibia, osteoclast numbers significantly increased at day 3, and peaked between days 15 and 23. In the tibia, however, the bone formation rates (BFR/BS) were significantly reduced on the 3rd and 7th post-surgical days compared with the start value for both the OVX and sham groups. The BFR/BS values in L5 did not decrease during the first 7 days in either group. The BFR/BS values were then increased for both L5 and the tibia after day 7. These data clearly demonstrated that the local bone turnover 7 days post-OVX was identical in the proximal tibia and the lumbar vertebra. In the proximal tibia, however, it may be suggested that the increased bone resorption and reduced formation within 7 days after OVX due to the combined effects of both an estrogen deficiency and the surgical intervention would possibly play a critical role in the greater magnitude of the trabecular bone loss.


Incidence of chromosome 3, 7, 10, 11, 17 and X disomy in mature human sperm nuclei as determined by nonradioactive in situ hybridization.
In situ hybridizations were performed on mature human sperm cells with biotin-labeled alpha-satellite DNA probes specific for chromosomes 3, 7, 10, 11, 17, and X in order to reveal the disomy rate for each of these chromosomes. A total of 76,253 sperm nuclei from seven healthy probands aged 23-57 years were analyzed. An average of 12,000 sperm nuclei (at least 1500 per donor) showing hybridization were scored with each probe. The disomy rate as indicated by two distinct hybridization signals turned out to be similar for all chromosomes, ranging from 0.31% to 0.34%. There were no significant interindividual differences and no age correlation in the frequency of disomic sperm cells between the donors.


Clearance and action of insulin during general or epidural anaesthesia.
Surgery performed under general anaesthesia induces impaired glucose tolerance together with comparatively low levels of insulin. This contrasts with the normal glucose tolerance and normal insulin levels found in patients operated upon under epidural anaesthesia. The aim of this study was to investigate insulin clearance and insulin action during surgery. Sixteen non-diabetic patients admitted for elective inguinal herniorrhaphy were operated under general anaesthesia (thiopentone, N2O/O2 (2/1), fentanyl, pancuronium bromide) or after high epidural blockade with mepivacaine. The clearance and hypoglycemic action of insulin were determined after a 2.5 min infusion of a physiologic dose of insulin. All patients were studied the day before operation and during surgery. The hypoglycemic action of insulin, expressed as % decrement from the pre-test blood glucose level, was unchanged during epidural anaesthesia but reduced during general anaesthesia (22.4 +/- 1.8% pre-operatively vs 7.5 +/- 1.3% intra-operatively, p < 0.01). The insulin resistance during general anaesthesia was associated with a decreased clearance of insulin (20.3 +/- 0.8 ml min(-1) kg(-1) pre-operatively vs 12.7 +/- 1.1 ml min(-1) kg(-1) intra-operatively, p < 0.01), whereas insulin clearance was normal during epidural anaesthesia. It is concluded that general anaesthesia, but not epidural anaesthesia, induces a reduction in both clearance and hypoglycemic action of insulin.


Clinical Profiles of Arteriolosclerosis and Alzheimer Disease at Mild Cognitive Impairment and Mild Dementia in a National Neuropathology Cohort.
We sought to evaluate early clinical differences between cerebral arteriolosclerosis (pARTE), Alzheimer disease (pAD), and AD with arteriolosclerosis (ADARTE). Using National Alzheimer's Coordinating Center neuropathology diagnoses, we defined pARTE (n=21), pAD (n=203), and ADARTE (n=158) groups. We compared demographics, medical history, psychometrics, neuropsychiatric symptoms, and apolipoprotein E (APOE) allele variants across neuropathology groups. Retrospective timepoints were first evaluation with Global Clinical Dementia Rating (CDR) score of 0.5 and 1.0, via the CDR Dementia Staging Instrument, corresponding to mild cognitive impairment (MCI) and mild dementia, respectively. In MCI, clinical differences were minimal but pARTE subjects were older, had later onset cognitive decline, and progressed less severely than pAD. In mild dementia, pAD subjects were younger and had earlier onset of decline. Neuropsychiatric (depression) and psychometric (Logical Memory Delayed Recall, Trails B) differences also emerged between the groups. In MCI, APOE4 associated with worse Logical Memory Delayed Recall in pAD and ADARTE. In mild dementia, APOE4 associated with better animal fluency in pAD, but with better Trails A performance and more neuropsychiatric symptoms (Neuropsychiatric Inventory Questionnaire) in ADARTE. Differences between pARTE, pAD, and ADARTE emerge at mild dementia rather than MCI. APOE4 has varied cognitive and psychiatric impact dependent on neuropathology group and stage.


Protective effect of Di'ao Xinxuekang capsule against doxorubicin-induced chronic cardiotoxicity.
Di'ao Xinxuekang capsule (DXXK) extracted from Dioscorea nipponica Makino is a well-known traditional Chinese herbal medicinal product widely used in the treatment of cardiovascular disease, such as myocardial ischemia and arrhythmia. The active ingredients of DXXK were also traditionally utilized for treating cardiovascular disease in the former Soviet Union after the 1960s. As a specific type of cardiovascular disease, doxorubicin (DOX)-induced cardiotoxicity is characterized by arrhythmia, myocardial ischemia, and heart failure. This study aimed to investigate the potential protective effect of DXXK against chronic cardiotoxicity induced by DOX. A mouse model of chronic cardiotoxicity induced by DOX and an in vitro model of DOX-induced myocardial damage were created to assess the protective effect of DXXK. Cardiac functional parameters, serum levels of CK-MB and LDH and cardiac histopathological indicators were determined in the mouse model. Moreover, cell viability was measured by the MTT method, and the effect of DXXK on the anticancer activity of DOX was also investigated by utilizing 4T1, HepG2, and H460 cell lines. Furthermore, the levels of markers of oxidative stress indexes (SOD, GSH, MDA) and inflammation (TNF-α, IL-1α) were measured using biochemical and Elisa kits, respectively. The level of ROS in H9c2 cardiomyocyte was determined by flow cytometry. The protein expression levels of HIF-1α and NF-κB p65 were measured by western blotting. Finally, molecular docking was performed to visualize the patterns of interactions between the effective molecule and targeted protein. DXXK alleviated DOX-induced chronic cardiotoxicity as shown by the reversal of changes in levels of myocardial enzymes and left ventricular function and structure. DXXK exhibits antioxidant and anti-inflammatory activities. We also observed that DXXK might increase the protein expression level of HIF-1α and decrease the protein expression level of NF-κB p65. Further results of in vitro experiments showed that DXXK could protect cardiomyocyte against DOX-induced production of ROS, but DXXK had no effect on the anticancer activity of DOX. The results of molecular docking showed that dioscin and pseudoprotodioscin were the top two compounds of DXXK, which had high affinity with HIF-1α and NF-κB p65. Our results indicated that DXXK could protect against cardiotoxicity induced by DOX and alleviate oxidative stress and inflammation in vivo and in vitro via the regulation of HIF-1α and down NF-κB p65.


Heterolytic dihydrogen activation by B(C6F5)3 and carbonyl compounds.
Aromatic carbonyl compounds in combination with B(C(6)F(5))(3) are able to activate H(2) heterolytically. The reactivity of the carbonyl-B(C(6)F(5))(3) adduct is initiated by its thermal dissociation into components. After H(2) addition, aromatic carbonyl compounds convert into aryl-substituted methanes or alcohols.


In silico prediction of prostaglandin D2 synthase inhibitors from herbal constituents for the treatment of hair loss.
Many herbal topical formulations have been marketed worldwide to prevent hair loss or promote hair growth. Certain in vivo studies have shown promising results among them; however, the effectiveness of their bioactive constituents remains unknown. Recently, prostaglandin D2 (PGD2) inhibition has been discovered as a pharmacological mechanism for treating androgenic alopecia (AGA). This present study was aimed to identify prostaglandin D2 synthase (PTGDS) inhibitors in traditional Chinese medicines (TCMs) for treating AGA. In this study, 389 constituents of 12 selected herbs were docked into 6 different crystal structures of PTGDS. The accuracy of the docking methods was successfully validated with experimental data from the ZINC In Man (Zim) database using receiver operating characteristic (ROC) studies. Seven essential drug properties were predicted for topical formulation: skin permeability, sensitisation, irritation, corrosion, mutagenicity, tumorigenicity and reproductive effects. Many constituents of the twelve herbs were found to have more advanced binding energies than the experimentally proved PTGDS inhibitors, but many of them were indicative of at least one type of skin adverse reactions, and exhibited poor skin permeability. Overall, ricinoleic acid, acteoside, amentoflavone, quercetin-3-O-rutinoside and hinokiflavone were predicted to be PTGDS inhibitors with good pharmacokinetic properties and minimal adverse skin reactions. These compounds have the highest potential for further in vitro and in vivo investigation with the aim of developing safe and high-efficacy hair loss treatment.


Validation of the blood pressure measurement technology used in the Novacor Diasys 3 (DIS-0001-00) upper arm device for ambulatory blood pressure measurement, according to the requirements of the AAMI/ANSI/ISO 81060-2:2013 standard (for both a general study and a cardiac-stress study in adults) and of the European Society of Hypertension International Protocol revision 2010.
The objective of this study was to determine the accuracy of the oscillometric blood pressure measurement technology of the Novacor Diasys 3 (model number DIS-0001-00) blood pressure monitor, intended for ambulatory blood pressure measurement, when used with the recommended Standard (ACC-0213-00), Large (ACC-0214-00) and Paediatric (ACC-0215-00) cuffs. The Novacor Diasys 3 (model number DIS-0001-00) was evaluated according to the requirements of the AAMI/ANSI/ISO 81060-2:2013 standard, including an additional cardiac-stress study, a requirement for ambulatory blood pressure measurement devices. It was also validated according to the requirements of the European Society of Hypertension International Protocol revision 2010. The protocol requirements for all thee studies were followed precisely. The Novacor Diasys 3 (model number DIS-0001-00) fulfilled all of the requirements for a pass in each of the three studies. In the primary AAMI/ANSI/ISO 81060-2:2013 study, the Criterion 1 errors were +3.9 mmHg ± 2.9 mmHg for SBP and +3.4 ± 2.5 mmHg for DBP. The Novacor Diasys 3 (model number DIS-0001-00), when used with the recommended cuffs, can be recommended for ambulatory blood pressure measurement in the adult population.


Predictive validity of endpoints used in electrophysiological modelling of migraine in the trigeminovascular system.
The trigeminovascular system has a pivotal role in the pathomechanism of migraine. The aim of the present study was to further develop existing models of migraine making them more suitable for testing the effects of compounds with presumed antimigraine activity in anaesthetised rats. Simultaneous recording of ongoing activity of spontaneously active neurons in the trigeminocervical complex as well as their discharges evoked by electrical stimulation of the dura mater via activation of A- and C-sensory fibres were carried out. Effects of sumatriptan, propranolol and topiramate were evaluated prior to and after application of a mixture containing inflammatory mediators on the dura. Propranolol (10 mg/kg s.c) and topiramate (30 mg/kg s.c.) resulted in a tendency to decrease the level of both spontaneous and evoked activity, while sumatriptan (1 mg/kg s.c.) did not exhibit any effect on recorded parameters. Application of an inflammatory soup to the dura mater boosted up spontaneous activity, which could be significantly attenuated by propranolol and topiramate but not by sumatriptan. In addition, all compounds prevented the delayed increase of spontaneous firing. In contrast to the ongoing activity, evoked responses were not augmented by inflammatory mediators. Nevertheless, inhibitory effect of propranolol and topiramate was evident when considering A- or C-fibre responses. Findings do not support the view that electrically evoked responses are useful for the measurement of trigeminal sensitization. It is proposed however, that inhibition of enhanced firing (immediate and/or delayed) evoked by inflammatory mediators as an endpoint have higher predictive validity regarding the clinical effectiveness of compounds.


Two technical aids for intermittent sterile catheterisation.
The use of a spray bottle for an antiseptic solution, and a method of attaching the catheter to a disposable urine bag are suggested and discussed.


Cholesterol-binding sequence is a key regulatory motif of cellular folding and conformational activation for C-reactive protein.
Human, rat, and mouse C-reactive protein (CRP) possess distinct expression patterns, but have similar conformations and conserved in vivo functions. We have previously demonstrated that this level-function mismatch is delicately tuned by the hidden activities of unfolded CRP. The cholesterol-binding sequence (CBS; a.a. 35-47) is a major functional motif exposed on monomeric CRP, which is the unfolded and activated conformation of CRP. We replaced the CBS of rat CRP with that of either mouse or human CRP, yielding two grafting mutants with unaffected pentameric assembly. However, these mutants exhibited altered cellular foldability and conformational activation efficiency that matched those of the CRP that provided the grafted CBS. These results indicate that CBS is a critical regulatory motif, whose variation maintains the pentameric assembly of CRP but derives distinct cellular foldabilities and conformational activation efficiencies, therefore helping to ensure that CRPs with various expression patterns exhibit overall conserved functions.


Decontamination of dental unit water systems with hydrogen peroxide.
Transmission of microbial pathogens to patients from water in dental units is a concern. To reduce this risk, the decontaminating efficiency of hydrogen peroxide was evaluated. Three percent hydrogen peroxide diluted 1 : 4 in distilled water (contact time 15 min) was used daily to disinfect the waterlines of a pilot unit previously contaminated with Pseudomonas aeruginosa or Staphylococcus aureus. The behaviour of the test bacteria was seen to differ over time. Staph. aureus numbers slowly decreased until only low numbers were recovered, after which the levels remained stable. Ps. aeruginosa abatement was more rapid and the density of the bacteria reached a peak when the circuit was empty. Staph. aureus and Ps. aeruginosa treated with hydrogen peroxide fell from 6 to 4 log. Treatment of dental unit waterlines with hydrogen peroxide was seen to be able to keep the number of the bacteria under control, as long as the treatment was repeated daily.


A re-evaluation of the ability of thiopental to identify cerebrospinal fluid in epidural catheter aspirate.
Sodium thiopental has been used to determine whether fluid aspirated from an epidural catheter is previously injected local anesthetic or cerebrospinal fluid (CSF). The purpose of this study was to test the efficacy of this test in distinguishing opioids from CSF. in vitro study. Laboratory of a university hospital. Three in vitro studies were performed. The first study tested for precipitation when thiopental was mixed with several commonly used epidural medications. Then, thiopental was mixed in combinations of opioids with local anesthetics to see if the opioid might prevent the precipitation of the local anesthetics. Finally, lidocaine was serially diluted and precipitation with thiopental was assessed. It was found that certain concentrations of opioids as well as normal saline do not precipitate with thiopental. In addition, the ratio of opioids to local anesthetic of 10:1 prevented precipitation when thiopental was added. Local anesthetics combined with cerebrospinal fluid in a 1:10 ratio produced a precipitate on mixing with thiopental. Use of thiopental to differentiate opioids from cerebrospinal fluid is unreliable. In addition, in some simulated situations, opioids may mask the presence of local anesthetic.


Validation of the qSOFA and CRB-65 in SARS-CoV-2-infected community-acquired pneumonia.
Prognostic accuracy of the quick sequential organ failure assessment (qSOFA) and CRB-65 (confusion, respiratory rate, blood pressure and age (≥65 years)) risk scores have not been widely evaluated in patients with SARS-CoV-2-positive compared to SARS-CoV-2-negative community-acquired pneumonia (CAP). The aim of the present study was to validate the qSOFA(-65) and CRB-65 scores in a large cohort of SARS-CoV-2-positive and SARS-CoV-2-negative CAP patients. We included all cases with CAP hospitalised in 2020 from the German nationwide mandatory quality assurance programme and compared cases with SARS-CoV-2 infection to cases without. We excluded cases with unclear SARS-CoV-2 infection state, transferred to another hospital or on mechanical ventilation during admission. Predefined outcomes were hospital mortality and need for mechanical ventilation. Among 68 594 SARS-CoV-2-positive patients, hospital mortality (22.7%) and mechanical ventilation (14.9%) were significantly higher when compared to 167 880 SARS-CoV-2-negative patients (15.7% and 9.2%, respectively). All CRB-65 and qSOFA criteria were associated with both outcomes, and age dominated mortality prediction in SARS-CoV-2 (risk ratio >9). Scores including the age criterion had higher area under the curve (AUCs) for mortality in SARS-CoV-2-positive patients (e.g. CRB-65 AUC 0.76) compared to SARS-CoV-2 negative patients (AUC 0.68), and negative predictive value was highest for qSOFA-65=0 (98.2%). Sensitivity for mechanical ventilation prediction was poor with all scores (AUCs 0.59-0.62), and negative predictive values were insufficient (qSOFA-65=0 missed 1490 out of 10 198 patients (∼15%) with mechanical ventilation). Results were similar when excluding frail and palliative patients. Hospital mortality and mechanical ventilation rates were higher in SARS-CoV-2-positive than SARS-CoV-2-negative CAP. For SARS-CoV-2-positive CAP, the CRB-65 and qSOFA-65 scores showed adequate prediction of mortality but not of mechanical ventilation.


Point-of-care (POC) measurement of coagulation after cardiac surgery.
Two different point-of-care (POC) systems for the monitoring of coagulation variables at the bedside were evaluated with regard to practicability, accuracy and costs. Prospective, descriptive study. Single-institutional, clinical investigation on an intensive care unit (ICU) of an urban, university-affiliated hospital. Eighty cardiac surgery patients were studied postoperatively. Arterial blood samples were drawn postoperatively on the ICU at different data points. Activated partial thromboplastin time (aPTT) and prothrombin time (PT) were measured using two POC systems (Thrombolytic Assessment System [TAS] and CoaguCheck Plus). At the same time coagulation parameters were measured by the central laboratory of the hospital. Measurements were carried out at different data points after cardiac surgery on the ICU. The direct and indirect costs of measuring aPTT/PT were also assessed. Bias analyses revealed good agreement of the POC-based monitoring of aPTT/PT with laboratory-based monitoring of coagulation (e. g. aPTT CoaguCheck: bias of -2.8 s with +/- 2 SD [limits of agreement] of +13.7 and -19.1 s). Mean turn-around time (TAT; time from blood sampling until availability of data for the ICU physicians) was significantly longer for the central laboratory-based coagulation monitoring (130 +/- 38 min) than for the two POC systems (aPTT-TAS: 9.6 +/- 2.7 min; aPTT-CoaguCheck: 6.5 +/- 1.9 min). Blood sampling at unfavorable times increased the TAT for laboratory-based measurements considerably. The direct costs for measuring aPPT and PT were significantly higher using both POC systems (aPTT-TAS: $4.84; aPTT-CoaguCheck: $4.34) than for the central laboratory ($1.59). Costs for transportation increased the laboratory-based monitoring considerably ($3.77). Both POC analyzers may reduce the potential for preanalytical errors associated with coagulation measurements at the central laboratory, hasten TAT significantly and may improve patient therapy by reducing inappropriate administration of blood products.


Alkaline ultrasonic irradiation-mediated boosted H2 production over O/N-rich porous carbon anchored Ru nanoclusters.
Developing efficient catalytic systems to boost hydrogen evolution from hydrolytic dehydrogenation of ammonia borane (AB) is of broad interest but remains a formidable challenge since the widespread usages of hydrogen have been considered as sustainable solutions to ensure future energy security. Herein, we developed an alkaline ultrasonic irradiation-mediated catalytic system with O/N-rich porous carbon supported Ru nanoclusters (NCs) (Ru/ONPC) to considerably boost the catalytic activity for hydrogen production from the hydrolytic dehydrogenation of AB. The uniformly distributed sub-2.0 nm Ru NCs on the ONPC were demonstrated to be efficient catalysts to boost hydrogen generation from the hydrolytic dehydrogenation of AB with the synergistic effect between ultrasonic irradiation and alkaline additive without any additional heating. An ultrahigh turnover frequency (TOF) of 4004 min-1 was achieved in the developed catalytic system, which was significantly higher than that of ultrasound-mediated AB hydrolysis without alkali (TOF: 485 min-1) and alkaline AB hydrolysis (TOF: 1747 min-1) without ultrasound mixing. The alkaline ultrasonic irradiation was beneficial for the cleavage of the OH bonds in the attacked H2O molecules catalyzed by the Ru/ONPC and thus considerably boost the catalytic hydrogen generation from AB. This study provides a tractable and ecofriendly pathway to promote the activity toward AB hydrolysis to release hydrogen.


Short-term outcome of neonates with congenital heart disease and diaphragmatic hernia treated with extracorporeal membrane oxygenation.
Major congenital heart disease (CHD) is seen in 10% to 15% of patients with congenital diaphragmatic hernia (CDH). Some neonates with CDH and major CHD are treated by surgery and some with extracorporeal membrane oxygenation (ECMO). Because of presumed poor survival, there is significant heterogeneity in management approaches for patients with CDH and associated CHD, and there is no published outcome data of patients who were placed on ECMO support. To examine outcomes of children with CDH with CHD supported with ECMO, Extracorporeal Life Support Organization (ELSO) registry was queried from 1998 to May 2010. There were a total of 3,342 deployments for CDH and 316 (9.5%) neonates with associated CHD. The median values are as follows: age at presentation, 1 (0 to 52) days; gestational age, 38 (29 to 42) weeks; birth weight, 3 (1.35 to 4.7) kg; admission to time to ECMO, 16 (0 to 1,220) hours; duration of ECMO, 194 (3 to 823) hours; time off of ECMO to extubation, 366 (0 to 7,934) hours; and time off of ECMO to death was 114 (0 to 7,272) hours. Initially, ECMO support was venoarterial in 91% (283 of 316), 5 were converted from venovenous to venoarterial ECMO. Overall survival to hospital discharge for all patients with CDH and CHD was 47% (148 of 316). Survival to hospital discharge for hypoplastic left heart syndrome and single-ventricle physiology was 55% (33 of 60), 48% (43 of 89) for ventricular septal defect, and 40% (24 of 60) for coarctation of the aorta patients. Patients with CDH and CHD supported with ECMO have had better than predicted short-term outcomes. In this cohort, overall survival of patient's with CDH with or without CHD was similar. Patients with single-ventricle physiology had similar short-term outcome to those with 2 ventricle physiology.


Ultrasound and CT diagnosis of intramural duodenal hematoma.
An 8-year-old boy with traumatic duodenal hematoma is reported. Diagnosis is easy if one is familiar with its typical findings in modern imaging modalities.


Economic evaluation of lifestyle interventions to treat overweight or obesity in children.
To estimate lifetime cost effectiveness of lifestyle interventions to treat overweight and obese children, from the UK National Health Service perspective. An adaptation of the National Heart Forum economic model to predict lifetime health service costs and outcomes of lifestyle interventions on obesity-related diseases. Hospital or community-based weight-management programmes. Hypothetical cohorts of overweight or obese children based on body mass data from the National Child Measurement Programme. Lifestyle interventions that have been compared with no or minimal intervention in randomized controlled trials (RCTs). Reduction in body mass index (BMI) standard deviation score (SDS), intervention resources/costs, lifetime treatment costs, obesity-related diseases and cost per life year gained. Ten RCTs were identified by our search strategy. The median effect of interventions versus control from these 10 RCTs was a difference in BMI SDS of -0.13 at 12 months, but the range in effects among interventions was broad (0.04 to -0.60). Indicative costs per child of these interventions ranged from £108 to £662. For obese children aged 10-11 years, an intervention that resulted in a median reduction in BMI SDS at 12 months at a moderate cost of £400 increased life expectancy by 0.19 years and intervention costs were offset by subsequent undiscounted savings in treatment costs (net saving of £110 per child), though this saving did not emerge until the sixth or seventh decade of life. The discounted cost per life year gained was £13 589. Results were broadly similar for interventions aimed at children aged 4-5 years and which targeted both obese and overweight children. For more costly interventions, savings were less likely. Interventions to treat childhood obesity are potentially cost effective although cost savings and health benefits may not appear until the sixth or seventh decade of life.


Cerebellar ataxia, hypogonadism and chorioretinopathy: molecular analysis of an Italian family.
This study aimed to determine if cerebellar ataxia, hypogonadism and chorioretinopathy (AHCR) is associated with mutations in mitochondrial DNA or in genes responsible for spinocerebellar ataxias (SCA1, SCA2, SCA3 and Friedreich's ataxia). Two brothers with cerebellar ataxia, hypogonadism and chorioretinopathy and their unaffected parents underwent molecular analysis for duplications and deletions in mitochondrial DNA (mtDNA), point mutations in the ATP ase 6 gene, and expansions of CAG repeats (at 6p22-p23, 12q24.1, 14q32.1) and of GAA repeats (at gene X25 on chromosome 9q13). The research was negative for all mutations. Our findings confirm that AHCR is a distinct disease within the inherited cerebellar ataxias.


Studies of chloroplast thylakoid proteins using monoclonal antibodies.
Several monoclonal antibodies have been produced against partially purified photosystem I reaction center complexes isolated from spinach chloroplasts. One of the clones was shown to be highly specific for the 28,000 and 27,000 dalton subunits of purified light harvesting chlorophyll a/b binding complex. Studies with thylakoids suggest at least a portion of the light harvesting chlorophyll a/b binding protein molecules are exposed on a normally inaccessible surface of the membrane.


Interactions of a beta-dipeptide with monovalent metal cations: crystal structures of (anthranoyl)anthranilic acid and its lithium, sodium and thallium salts.
X-ray crystal structure analyses have been performed on the beta-dipeptide (anthranoyl)anthranilic acid [HAnthAnthOH] and its lithium, sodium and thallium salts [HAnthAnthOM] to give a first set of data for this representative model ligand. Crystals of the beta-dipeptide are orthorhombic, space group Pca2(1). The unit cell contains two molecules of (anthranoyl)anthranilic acid which form a dimer via hydrogen bonds. The components of the beta-dipeptide are rotated into the trans-conformation which allows for internal hydrogen bonds. The pKS value of (anthranoyl)anthranilic acid (9.80+/-0.14) shows a slight decrease as compared to anthranilic acid; the metal salts can therefore be prepared by direct neutralization of the beta-dipeptide with metal hydroxides or carbonates. The alkali compounds crystallize as the trihydrates [HAnthAnthOM(H2O)3, M=Li, Na] in the triclinic space group p1. Both metal ions show a clear preference for water molecules over the (anthranoyl)anthranilate anions as ligands in their coordination spheres. As a consequence, the [HAnthAnthO]- anions are only partially involved in metal complexation. The cell plots of both compounds exhibit a stacking with an alternation of oppositely charged layers. The negatively charged layers are composed exclusively of (anthranoyl)anthranilate anions. The thallium compound crystallizes as the hemihydrate [HAnthAnthOTl(H2O)0.5] in the monoclinic space group C2/c. In the dinuclear units, the thallium ions accommodate one nitrogen and four oxygen atoms of the anions in their coordination sphere and in addition entertain weak Tl-arene contacts. In contrast to the alkali compounds, the water molecules are not involved in metal complexation, but contribute to a network of hydrogen bonding.


Resident and Fellow Participation Does Not Affect Short-Term Postoperative Complications After Distal Radius Fracture Fixation.
Background Complications after open reduction internal fixation (ORIF) for distal radius fractures (DRF) are well documented, but the impact of trainee involvement on postoperative outcomes has not been studied. Questions Does trainee involvement affect postoperative complication rates and length of hospital stay? Methods The American College of Surgeons National Surgical Quality Improvement Program was queried from 2006 to 2012 for patients undergoing DRF ORIF. A 1:1 propensity score matched resident/fellow involved cases to attending-only cases. Demographics, length of stay, and postoperative complications were compared between the two groups. Logistic regression was used to evaluate independent predictors of adverse events and to evaluate cases with and without trainee involvement. Results Overall, 3,003 patients underwent DRF ORIF from 2006 to 2012. After matching, 1,150 cases (50% with resident/fellow involvement) were included. The overall rate of adverse events was 4.4% (46/1,050). There were no significant differences in the short-term complication rate in trainee-involved (2.3%) versus attending-only cases (3.9%) ( p = 0.461). For ORIF of DRF, there were no significant differences, between attending-only cases and resident/fellow-involved cases, with regard to short-term major complications ( p = 0.720) or minor complications ( p = 0.374). Length of hospital stay was similar between cohorts (1.22 vs. 0.98 days) ( p = 0.723). On multivariate analysis, trainee involvement was not an independent predictor of minor, major, or any complication after DRF fixation after controlling for multiple independent factors (all p > 0.364). Discussion Trainee participation in DRF ORIF is not associated with increased risk of short-term (30 days) medical or surgical postoperative complications. Level of Evidence This is a Level IV case-control study.


Prematurely delivering mothers show reductions of lachnospiraceae in their gut microbiomes.
Preterm birth is the leading cause of perinatal morbidity and mortality. Despite evidence shows that imbalances in the maternal microbiome associates to the risk of preterm birth, the mechanisms underlying the association between a perturbed microbiota and preterm birth remain poorly understood. Applying shotgun metagenomic analysis on 80 gut microbiotas of 43 mothers, we analyzed the taxonomic composition and metabolic function in gut microbial communities between preterm and term mothers. Gut microbiome of mothers delivering prematurely showed decreased alpha diversity and underwent significant reorganization, especially during pregnancy. SFCA-producing microbiomes, particularly species of Lachnospiraceae, Ruminococcaceae, and Eubacteriaceae, were significantly depleted in preterm mothers. Lachnospiraceae and its species were the main bacteria contributing to species' differences and metabolic pathways. Gut microbiome of mothers delivering prematurely has altered and demonstrates the reduction of Lachnospiraceae.


Caries prevalence among HIV-infected children between four and ten years old at a paediatric virology out-patients ward in Johannesburg, Gauteng Province, South Africa.
There remains controversy in the literature as to whether children with HIV are at greater risk for caries than healthy children. To determine the caries prevalence and unmet treatment needs (UTN) in a cohort of HIV+ive children between the ages of four and ten years who were attending the Charlotte Maxeke Paediatric Virology out-patients ward and to compare the results with the data of the National Children's Oral Health Survey (NCOHS). This descriptive, analytic study comprised of a sample of 277 children attending the Paediatric Virology out patients ward at the Charlotte Maxeke Hospital over a one year period. The caries status was measured using WHO guidelines and criteria. Among the 93 children aged between four and five years, the caries prevalence of the primary dentition was 70.9%; the dmft was 5.1 and the UTN was 99.6%. In the 62 six year olds and 122 seven to ten year olds, the caries prevalence in the primary teeth was 62.9% and 67.2%; the dmft was 4.2 and 4 and the UTN 100% and 87.8% respectively. The mean dmft of the four, five and six year olds was significantly higher than those reported in the NCOHS. The four, five and sx-year old HIV positive children had a 1.4 times higher risk of caries development than children from the general population (p < 0.002). This cohort of HIV-infected children had significantly higher caries prevalence, dmft and UTN than did children from the general population.


Plant essential oils improve growth performance by increasing antioxidative capacity, enhancing intestinal barrier function, and modulating gut microbiota in Muscovy ducks.
Essential oils (EO) are known for their antioxidant, anti-inflammatory, antimicrobial, and growth-promoting properties. However, data rgarding their impact on the intestinal health and gut microbiota of ducks remain limited. Thus, this study aimed to investigate the effects of plant EO on the growth performance, intestinal health, and gut microbiota of Muscovy ducks. A total of 360 healthy male Muscovy ducks aged 1 d were randomly divided into 4 groups with 6 replicates and 15 ducks per replicate. Ducks were fed basal diets supplemented with 0, 100, 200, or 300 mg/kg EO. The results showed that 200 mg/kg EO supplementation significantly (P < 0.05) increased the final body weight and average daily gain, while significantly (P < 0.05) decreased the feed conversion ratio during the 56-d experimental period. Furthermore, dietary 200 mg/kg EO significantly (P < 0.05) enhanced antioxidant capacity and immune function and improved the barrier function of the intestine. Additionally, 16S rDNA sequencing analysis results showed that 200 mg/kg EO favorably modulated the cecal microbial diversities and composition evidenced by the increased (P < 0.05) the abundances of short-chain fatty acid-producing bacteria (e.g., Subdoligranulum and Shuttleworthia) and decreased (P < 0.05) abundances of potential enteric pathogenic bacteria (e.g., Alistipes, Eisenbergiella, and Olsenella). The relative abundance of beneficial bacteria was positively correlated with antioxidant, immune, and barrier function biomarkers. Overall, these findings revealed that dietary supplementation with 200 mg/kg EO had several potentially beneficial effects on the growth performance of Muscovy ducks by improving antioxidant capacity, enhancing the intestinal barrier function and favorably modulating gut microbiota.


Biomonitoring of ochratoxin A in grain workers.
Handling agricultural commodities such as grain can result in an inhalation of mycotoxin-containing dusts. Ochratoxin A (OTA) is particularly well suited for biomonitoring studies due to its long half-life in blood, and served as a marker toxin to investigate whether or not exposure to dusts in occupational contexts may result in elevated OTA blood serum levels. OTA analysis was performed for blood samples (n=61) obtained from a cohort of male workers employed at granaries of several grain handling companies in Germany. OTA was analyzed in plasma extracts by HPLC with fluorimetric detection; calibration curves were run for each batch of samples collected between July 2005 and March 2006, and the level of detection was 0.05 ng/ml plasma. The OTA plasma levels of the 61 grain workers ranged between 0.07 ng/ml and 0.75 ng/ml. The mean (0.28±0.13 ng/ml) and median (0.26 ng/ml) OTA value for this cohort was similar to average values previously reported for the German population. Our results gave no indication that OTA in excess of those originating from typical dietary sources was ingested by these workers. Although measurable OTA concentrations have been found in dust samples collected at the corresponding workplaces (Mayeret al, this issue), the biomonitoring data do not provide evidence for a significant inhalatory burden of OTA in grain workers. Since deoxynivalenol and zearalenone were also detected in the dust samples in concentrations much higher than that of OTA, additional research should try to assess the potential relevance of an inhalation exposure to these mycotoxins.


Correction to: A loss of consciousness in a teenage girl with anorexia nervosa, due to polydipsia: case report and a minireview.
AN was the most frequent cause of hospitalization within all ED and suicide attempt-related hospitalizations were most common among patients with AN [9].


Phosphorus supplementation of Nellore steers fed Yaragua/Stylo mixture in the Peruvian tropics.
Twenty-four yearling 11-month old Nellore steers initially weighing 180 kg were assigned to three treatments in a randomised complete block experiment lasting 392 days. Animals grazed continuously either Yaragua grass (Hyparrhenia rufa) or Yaragua/Stylo legume (Stylosanthes guianensis) and received the following treatments: A) Control, Yaragua plus common salt, B) Yaragua/Stylo plus common salt, and C) Yaragua/Stylo plus dicalcium phosphate/common salt (1:1). Mineral consumption in the three groups averaged 52 g per animal day-1. At 13 months daily liveweight gains/steer were 0.182, 0.409 and 0.483 kg for treatments of Yaragua, Yaragua/Stylo, and Yaragua/Stylo plus dicalcium phosphate/common salt mixture. Daily liveweight gains per ha were 0.488, 1.289, and 1.522 kg steer-1 for Yaragua, Yaragua/Stylo plus common salt and Yaragua/Stylo plus dicalcium phosphate/common salt. Steers receiving a legume (stylo) in the diet more than doubled weight gains (P less than 0.05) compared to controls with dicalcium phosphate further (P less than 0.05) increasing these gains.


Intracellular features of type II procollagen and chondroitin sulfate proteoglycan synthesis in chondrocytes.
The intracellular compartments of chondrocytes involved in the synthesis and processing of type II procollagen and chondroitin sulfate proteoglycan (CSPG) monomer were investigated using simultaneous double immunofluorescence and lectin localization reactions. Type II procollagen was distributed in vesicles throughout the cytoplasm, whereas intracellular precursors of CSPG monomer were accumulated in the perinuclear cytoplasm. In this study, cytoplasmic vesicles that stained intensely with antibodies directed against CSPG monomer but did not react with type II collagen antibodies, also were observed. A monoclonal antibody, 5-D-4, that recognizes keratan sulfate determinants was used to identify the Golgi complex (the site of keratan sulfate chain elongation). Staining with 5-D-4 was restricted to the perinuclear cytoplasm. The vesicles outside the perinuclear cytoplasm that stained intensely with antibodies to CSPG monomer did not react with 5-D-4. Fluorescent lectins were used to characterize further subcellular compartments. Concanavalin A, which reacts with mannose-rich oligosaccharides, did not stain the perinuclear region, but it did stain vesicles throughout the rest of the cytoplasm. Because mannose oligosaccharides are added cotranslationally, the stained vesicles throughout the cytoplasm presumably correspond to the rough endoplasmic reticulum. Wheat germ agglutinin, which recognizes N-acetyl-D-glucosamine and sialic acid (carbohydrates added in the Golgi), stained exclusively the perinuclear cytoplasm. By several criteria (staining with the monoclonal antibody 5-D-4 and with wheat germ agglutinin), the perinuclear cytoplasm seems to correspond to the Golgi complex. The cytoplasmic vesicles that react with anti-CSPG monomer and not with anti-type II collagen contain precursors of CSPG monomer not yet modified by Golgi-mediated oligosaccharide additions (because they are not stained with wheat germ agglutinin or with the anti-keratan sulfate antibody); these vesicles may have a unique function in the processing of CSPG.


Relationships between nutrient intake, nutritional status and activity levels in an elderly and in a younger population; a comparison of physically more active and more inactive people.
Differences in absolute nutrient intakes, nutrient densities, and nutritional status between more physically active and more physically inactive elderly persons were analyzed from data of the Heidelberg-Michelstadt-Berlin Study. Comparisons were made in the different sex groups for older persons, the same comparisons were made for a group of younger persons. Although there was no significant statistical difference, the active persons had higher absolute energy intakes compared with inactive persons in all groups, except in the younger female group. Active older women have statistically significant higher vitamin B2, iodine, and calcium intakes than less active older women. Active older men have higher energy, carbohydrate, carotene, vitamin E, vitamin C, and calcium intakes than the less active older men. A totally different pattern of intakes is seen in the group of younger persons. The more active younger women show lower absolute intakes of vitamin A, vitamin E, vitamin B1, niacin, vitamin B6, vitamin B12, and sodium in comparison with the less active young women. Active young men show higher iodine intakes compared with the inactives. The differences in intakes however are not reflected in the nutritional status. The nutritional status of more active people is therefore neither endangered nor improved in comparison with less active.


A midcourse review of the healthy people 2010: 21 critical health objectives for adolescents and young adults.
As part of Healthy People 2010, a national consensus panel identified 21 Healthy People 2010 objectives as critical to adolescent and young adult health. These objectives span six areas: mortality, unintentional injury, violence, mental health and substance use, reproductive health, and the prevention of chronic disease during adulthood. Progress on these objectives was reviewed as part of the Healthy People 2010 Midcourse Review. The review found little or no improvement on most objectives. Expert recommendations call for broad, population-based efforts to improve adolescent health. However, changes in health policy are largely issue-based and occur incrementally.


Non-invasive aneurysm detection using digital signal processing.
The attributes and performance expectations of a relatively low cost, non-invasive, aneurysm detection system have been studied. The developed system required that bio-acoustic data be captured at the patients' eyes, conditioned, transformed into the frequency domain, and analysed in some systematic fashion. It was admitted that the signal transducers were in need of improvement. Several low cost spectral analysers were built and tested. This system transformed the patient's bio-acoustic signal into a power spectrum. Features, representative of the patient's medical state, were extracted from the power spectrum and were input to a double-linked tree structure. Together with the medical class information, the structure can be searched to find the best statistical estimate of a patient's medical status. Experiment on generated and patient data, support the validity of the chosen diagnostic scheme.


Estimate of vitamin A in the guinea pig cochlea.
Microfluorometric estimates of the membranous structures of the freeze-dried guinea pig cochlea have demonstrated that vitamin A is present in these tissues at a concentration of 21.2 microgram/gm (SD +/- 4.77 microgram) which is approximately ten times the vitamin A concentration in most other tissues.


Ni[(EPiPr2)2N]2 complexes: stereoisomers (E = Se) and square-planar coordination (E = Te).
The reaction of ((i)Pr 2PE) 2NM.TMEDA (M = Li, E = Se; M = Na, E = Te) with NiBr 2.DME in THF affords Ni[(SeP (i)Pr 2) 2N] 2 as either square-planar (green) or tetrahedral (red) stereoisomers, depending on the recrystallization solvent; the Te analogue is obtained as the square-planar complex Ni[(TeP (i)Pr 2) 2N] 2.


Effect of mutation of glycosylation sites on the Na+ dependence of steady-state and transient currents generated by the neuronal GABA transporter.
The GABA (gamma-aminobutyric acid) transporter (GAT1) belongs to a superfamily of secondary active uptake systems for neurotransmitters that depend on the electrochemical gradients for Na+ and Cl-. In the GAT1, two Na+ ions and one Cl- ion are co-transported with one GABA molecule. Steady-state transport activity and transient charge movements during partial reactions of the transport cycle of the GAT1 of mouse brain expressed in Xenopus oocytes were investigated by two-electrode voltage clamp. Functional expression was demonstrated by Na+-dependent [3H]GABA uptake. Effects of mutation of two out of three N-glycosylation sites located in the extracellular loop between transmembrane domains 3 and 4 (Asn176, Asn181, Asn184) were analysed. Simultaneous substitution of two Asn by Asp leaves the transport system intact but leads to a reduction in turnover and complex changes in the interaction of external Na+ with the transport protein. If Asn176 is mutated to Asp and simultaneously Asn181 to Gly, no transport and no charge movements can be detected. In conclusion, mutations of the glycosylation sites result in altered transport, and the local conformation at Asn181 is critical for expression of transport activity.


Formulation optimization of photocrosslinked polyacrylic acid modified with 2-hydroxyethyl methacrylate hydrogel as an adhesive for a dermatological patch.
A photopolymerization technique was applied in the preparation of a hydrogel composed of polyacrylic acid (PAA) in which 2-hydroxyethyl methacrylate (HEMA) was modified. The formulation of photocrosslinked PAA modified with HEMA hydrogel as an adhesive for a dermatological patch was optimized based on the simultaneous optimization technique. Photocrosslinked PAA modified with HEMA hydrogels that retained a large amount of water, above 85%, were successfully prepared. Based on the analysis of ANOVA, the gel strength and adhesiveness increased with an increase in the degree of modification with HEMA and the concentration of PAA modified with HEMA in the aqueous solution. For the optimization study, the modification with HEMA and the concentration of initiator were selected as causal factors. Gel yield, probe tack, degree of swelling and turbidity were selected as response variables. A set of causal factors and response variables was used as a tutorial date for the prediction of optimal formulation with a quadratic regression model, an artificial neural network (ANN) and a multivariate spline interpolation (MSI). Response surfaces generated with MSI well represented the nonlinear relationship between the factors and the responses, and all the observed values of the response variables coincided with the predictions. A high functional photocrosslinked PAA modified with HEMA hydrogel as an adhesive for a dermatological patch was successfully created using the simultaneous optimization technique incorporating MSI.


Astrocytic characteristics of oligodendroglioma. Fine structural and immunohistochemical studies of two cases.
Two oligodendrogliomas were studied by light and electron microscopy. Additionally, an immunohistochemical study for glial fibrillary acidic protein (GFAP) was carried out. Some tumor cells exhibited glial filaments and perivascular end-feet, as on the one hand is characteristic of astrocytes, and glycogen granules and zonulae adherents which on the other hand are often seen in astrocytes but rarely in oligodendrocytes. Tumor cells with or without astrocytic characteristics showed the common fine structures and appeared to be on the same cell line. Our fine structural and immunohistochemical findings suggest that oligodendroglioma cells are of an astrocytic nature.


Influence of postural changes on haemodynamics in internal carotid artery bifurcation aneurysm using numerical methods.
Cerebral intracranial aneurysms are serious problems that can lead to stroke, coma, and even death. The effect of blood flow on cerebral aneurysms and their relationship with rupture are unknown. In addition, postural changes and their relevance to haemodynamics of blood flow are difficult to measure in vivo using clinical imaging alone. Computational simulations investigating the detailed haemodynamics in cerebral aneurysms have been developed in recent times not only to understand the progression and rupture but also for clinical evaluation and treatment. In the present study, the haemodynamics of a patient-specific case of a large aneurysm on the left side internal carotid bifurcation (LICA) and no aneurysm on the right side internal carotid bifurcation (RICA) was investigated. The simulation of these patient-specific models using fluid-structure interaction provides a valuable comparison of flow behavior between normal and aneurysm models. The influences of postural changes were investigated during standing, sleeping, and head-down (HD) position. Significant changes in flow were observed during the HD position and quit high arterial blood pressure in the internal carotid artery (ICA) aneurysm model was established when compared to the normal ICA model. The velocity increased abruptly during the HD position by more than four times (LICA and RICA) and wall shear stress by four times (LICA) to ten times (RICA). The complex spiral flow and higher pressures prevailing within the dome increase the risk of aneurysm rupture.