On dental health in Icelandic children. Observations during a clinical dentifrice trial.
Dental health and the relative caries preventive effect of different fluoride dentifrice formulations were assessed in an Icelandic child population. For a cross sectional study 1370 children, aged 11 and 12 years were examined for caries and periodontal conditions employing standardized methods. Longitudinal data were obtained from 1161 children, participating in a three-year dentifrice trial. Randomly selected subgroups were employed to study salivary levels of mutans streptococci and lactobacilli, consumption of high-sucrose products and enamel fluoride content in relation to caries experience. Relative caries preventive effect of anticalculus agents (HEBP and AHBP) and lowered fluoride concentration (250 ppm) in dentifrices were evaluated in a three-year double blind randomized clinical trial. At the baseline examination a comparatively high mean caries prevalence (DFS 9.9) was registered. Longitudinal observations showed a mean caries increment of 10.5 surfaces during a three-year period. Simultaneously an improvement of gingival health was observed. A majority of children harbored mutans streptococci (98%) and lactobacilli (92%). High numbers of either microorganism were associated with high caries prevalence. S. sobrinus carriers were more frequent among children with high numbers of CFU per ml saliva. The consumption of sugar-containing products was generally frequent. Higher caries increment was associated with consumption of sweets and bakery products during mealtimes. The fluoride content of surface enamel was comparatively low, reflecting scarce post eruptive exposure. Dentifrice, containing 250 ppm fluoride showed significantly lower caries preventive effect compared to 1000 ppm sodium fluoride and MFP formulations. Addition of anticalculus agents (biphosphonates) had no negative effect on reducing caries increment. These studies show that dental caries constitutes a major health problem among Icelandic children, where high sugar consumption and comparatively low exposure to fluoride appear to play major roles. The use of fluoride dentifrice has not been able to limit caries development.


Propensity Score Analysis of Radical Hysterectomy Versus Definitive Chemoradiation for FIGO Stage IIB Cervical Cancer.
The aim of this study was to compare the outcomes and toxicities of radical hysterectomy (RH) and definitive chemoradiation (CRT) for International Federation of Gynecology and Obstetrics (FIGO) stage IIB cervical cancer. A retrospective analysis was performed on FIGO stage IIB patients who underwent RH with adjuvant radiotherapy (surgery group) or intended to receive CRT (CRT group). The distributions of disease-free survival (DFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Propensity score matching (PSM) was performed for the 2 groups based on age, tumor diameter, histological type, and pelvic node metastasis in pretreatment imaging tests. Median follow-up times were 58 months in the surgery group (n = 75) and 55 months in the CRT group (n = 65). Propensity score matching identified 37 patients with similar characteristics from each group. Significant differences were observed in the ratio of the chemotherapy combination between the surgery and CRT groups before (47% vs 98%) and after PSM (51% vs 100%). Five-year DFS rates were slightly higher in the surgery group than in the CRT group before PSM (69% vs 58%, P = 0.30) but were similar after PSM (76% vs 82%, P = 0.36). Five-year OS rates were similar between the surgery and CRT groups before (70% vs 75%, P = 0.59) and after PSM (78% vs 77%, P = 0.97). The results of multivariate analyses also showed that neither DFS nor OS was associated with the treatment modalities regardless of PSM. The incidence of late toxicities grade 2 or greater was similar between the surgery and CRT groups before (17% vs 23%, P = 0.31) and after PSM (19% vs 24%, P = 0.78). The results of this study suggest that RH with adjuvant radiotherapy and definitive CRT are equivalent treatment options for patients with FIGO stage IIB cancer. However, prospective larger studies are needed to confirm this.


Identification of hospital cost drivers using sparse group lasso.
Public hospital spending consumes a large share of government expenditure in many countries. The large cost variability observed between hospitals and also between patients in the same hospital has fueled the belief that consumption of a significant portion of this funding may result in no clinical benefit to patients, thus representing waste. Accurate identification of the main hospital cost drivers and relating them quantitatively to the observed cost variability is a necessary step towards identifying and reducing waste. This study identifies prime cost drivers in a typical, mid-sized Australian hospital and classifies them as sources of cost variability that are either warranted or not warranted-and therefore contributing to waste. An essential step is dimension reduction using Principal Component Analysis to pre-process the data by separating out the low value 'noise' from otherwise valuable information. Crucially, the study then adjusts for possible co-linearity of different cost drivers by the use of the sparse group lasso technique. This ensures reliability of the findings and represents a novel and powerful approach to analysing hospital costs. Our statistical model included 32 potential cost predictors with a sample size of over 50,000 hospital admissions. The proportion of cost variability potentially not clinically warranted was estimated at 33.7%. Given the financial footprint involved, once the findings are extrapolated nationwide, this estimation has far-reaching significance for health funding policy.


The effect of increased intra-abdominal pressure on orbital subarachnoid space width and intraocular pressure.
In accordance with the trans-lamina cribrosa pressure difference theory, decreasing the trans-lamina cribrosa pressure difference can relieve glaucomatous optic neuropathy. Increased intracranial pressure can also reduce optic nerve damage in glaucoma patients, and a safe, effective and noninvasive way to achieve this is by increasing the intra-abdominal pressure. The purpose of this study was to observe the changes in orbital subarachnoid space width and intraocular pressure at elevated intra-abdominal pressure. An inflatable abdominal belt was tied to each of 15 healthy volunteers, aged 22-30 years (12 females and 3 males), at the navel level, without applying pressure to the abdomen, before they laid in the magnetic resonance imaging machine. The baseline orbital subarachnoid space width around the optic nerve was measured by magnetic resonance imaging at 1, 3, 9, and 15 mm behind the globe. The abdominal belt was inflated to increase the pressure to 40 mmHg (1 mmHg = 0.133 kPa), then the orbital subarachnoid space width was measured every 10 minutes for 2 hours. After removal of the pressure, the measurement was repeated 10 and 20 minutes later. In a separate trial, the intraocular pressure was measured for all the subjects at the same time points, before, during and after elevated intra-abdominal pressure. Results showed that the baseline mean orbital subarachnoid space width was 0.88 ± 0.1 mm (range: 0.77-1.05 mm), 0.77 ± 0.11 mm (range: 0.60-0.94 mm), 0.70 ± 0.08 mm (range: 0.62-0.80 mm), and 0.68 ± 0.08 mm (range: 0.57-0.77 mm) at 1, 3, 9, and 15 mm behind the globe, respectively. During the elevated intra-abdominal pressure, the orbital subarachnoid space width increased from the baseline and dilation of the optic nerve sheath was significant at 1, 3 and 9 mm behind the globe. After decompression of the abdominal pressure, the orbital subarachnoid space width normalized and returned to the baseline value. There was no significant difference in the intraocular pressure before, during and after the intra-abdominal pressure elevation. These results verified that the increased intra-abdominal pressure widens the orbital subarachnoid space in this acute trial, but does not alter the intraocular pressure, indicating that intraocular pressure is not affected by rapid increased intra-abdominal pressure. This study was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR-ONRC-14004947).


The puzzle of bond length variation in substituted cyclobutenes. A new example: molecular structure and conformations of 1,2-dimethoxy-3,3,4,4-tetrafluorocyclobut-1-ene.
The structure and composition of 1,2-dimethoxy-3,3,4,4-tetrafluorocyclobut-1-ene (DMCB) have been measured by electron diffraction from the gas at a temperature of 370 K with the help of auxiliary data from molecular orbital and normal coordinate calculations, the former at several levels of theory and basis-set size, most importantly B3LYP/cc-pVTZ. The compound was found to exist primarily as a rotamer of C(s) symmetry (ca. 98%; 2sigma = 11%) with the remainder one of C(2v) symmetry; theory predicts about 88% C(s). Values for some of the more important parameters (r(g)/A; angle(alpha)/deg) of the C(s) form are r(C=C) = 1.337(21), r(C1-C4) = 1.496(8), r(C2-C3) = 1.501(8), r(C3-C4) = 1.567(12), r(C1-O) = 1.318(12), r(C2-O) = 1.340(12), r(C3-F) = 1.375(4), r(C4-F) = 1.368(4), angle(ave)(C=C-C) = 94.4(4), angle(ave)(C=C-O) = 133.5(12), angle(ave)(C-O-C) = 119.6(13), and angle(ave)(F-C-F) = 104.4(7). Surprisingly, although electron-diffraction values for the fluorinated C3-C4 bond in other cyclobutenes are greater than that for cyclobutene itself, that is not the case for DMCB where it is found to be about the same. Details of the DMCB structure, together with possible reasons for the observed variations in the length of the C3-C4 bond in fluorinated cyclobutene-like molecules, are discussed.


Controlling Electronic Transitions in Fullerene van der Waals Aggregates via Supramolecular Assembly.
Morphologies crucially determine the optoelectronic properties of organic semiconductors. Therefore, hierarchical and supramolecular approaches have been developed for targeted design of supramolecular ensembles of organic semiconducting molecules and performance improvement of, e.g., organic solar cells (OSCs), organic light emitting diodes (OLEDs), and organic field-effect transistors (OFETs). We demonstrate how the photonic properties of fullerenes change with the formation of van der Waals aggregates. We identified supramolecular structures with broadly tunable absorption in the visible spectral range and demonstrated how to form aggregates with targeted visible (vis) absorption. To control supramolecular structure formation, we functionalized the C60-backbone with polar (bis-polyethylene glycol malonate-MPEG) tails, thus yielding an amphiphilic fullerene derivative that self-assembles at interfaces. Aggregates of systematically tuned size were obtained from concentrating MPEGC60 in stearic acid matrices, while different supramolecular geometries were provoked via different thin film preparation methods, namely spin-casting and Langmuir-Blodgett (LB) deposition from an air-water interface. We demonstrated that differences in molecular orientation in LB films (C2v type point group aggregates) and spin-casting (stochastic aggregates) lead to huge changes in electronic absorption spectra due to symmetry and orientation reasons. These differences in the supramolecular structures, causing the different photonic properties of spin-cast and LB films, could be identified by means of quantum chemical calculations. Employing supramolecular assembly, we propounded that molecular symmetry in fullerene aggregates is extremely important in controlling vis absorption to harvest photons efficiently, when mixed with a donor molecule, thus improving active layer design and performance of OSCs.


Solution-grown organic single-crystalline donor-acceptor heterojunctions for photovoltaics.
Organic single crystals are ideal candidates for high-performance photovoltaics due to their high charge mobility and long exciton diffusion length; however, they have not been largely considered for photovoltaics due to the practical difficulty in making a heterojunction between donor and acceptor single crystals. Here, we demonstrate that extended single-crystalline heterojunctions with a consistent donor-top and acceptor-bottom structure throughout the substrate can be simply obtained from a mixed solution of C60 (acceptor) and 3,6-bis(5-(4-n-butylphenyl)thiophene-2-yl)-2,5-bis(2-ethylhexyl)pyrrolo[3,4-c]pyrrole-1,4-dione (donor). 46 photovoltaic devices were studied with the power conversion efficiency of (0.255±0.095)% under 1 sun, which is significantly higher than the previously reported value for a vapor-grown organic single-crystalline donor-acceptor heterojunction (0.007%). As such, this work opens a practical avenue for the study of organic photovoltaics based on single crystals.


Reconstitution and partial purification of several Na+ cotransport systems from renal brush-border membranes. Properties of the L-glutamate transporter in proteoliposomes.
Brush-border membranes of renal proximal tubules were solubilized with deoxycholate and some proteins were separated and incorporated into proteoliposomes by a reconstitution procedure which was analyzed in detail. The proteoliposomes contained mainly polypeptides with molecular weights of 152,000, 94,000, and 52,000, each of which could be separated further into homologous polypeptides with different isoelectric points. In the proteoliposomes, Na+ cotransport systems for D-glucose, acidic and neutral amino acids, and mono- and dicarboxylic acids were demonstrated by showing that due to an inwardly directed Na+ gradient the substrate concentrations in the proteoliposomes increased significantly over their respective equilibrium values. Using inhibition experiments, selectivity of the different transporters could be demonstrated. Studying the reconstituted L-glutamate transporter in detail, countertransport of L-glutamate and K+ was shown (i) at Na+ equilibrium the intraliposomal L-glutamate concentration increased significantly over the equilibrium value if an outside-directed K+ gradient was applied; (ii) Rb+ influx was significantly stimulated by the outflux of L-glutamate. By applying a K+ diffusion potential across the liposomal membrane by addition of valinomycin it could be shown that during L-glutamate transport in the presence of Na+ and K+ positive charge is transferred together with L-glutamate and Na+. The apparent Km value of L-glutamate uptake driven by concentration differences of 89 mM Na+ (out greater than in) and 89 mM K+ (in greater than out) was 26.3 +/- 1.3 microM. The Vmax value of 70.2 +/- 2.3 pmol X mg of protein-1 X S-1 was half the value measured in intact membranes.


New insights into mononuclear phagocyte biology from the visual system.
Major advances in mononuclear phagocyte biology have been made but key questions pertinent to their roles in health and disease remain, including in the visual system. One problem concerns how dendritic cells can trigger immune responses from certain tightly regulated immune- privileged sites of the eye. Another, albeit separate, problem involves whether there are functional specializations for microglia versus monocytes in retinal neurodegeneration. In this Review, we examine novel insights in eye immune privilege and, separately, we discuss recent inroads concerning retinal degeneration. Both themes have been extensively studied in the visual system and show parallels with recent findings concerning mononuclear phagocytes in the central nervous system and in the periphery.


Dynamics of Thermocapillary-Driven Motion of Liquid Drops.
The thermocapillary migration of a drop placed on a solid plate is examined. The Brochard model using the lubrication approximation provides both Marangoni and Poiseuille flow components. The present 2D model extends Brochard analysis and provides a solution for the dynamics of drop migration using extended boundary conditions at the advancing and receding contact lines to account for both Marangoni and Poiseuille flow components, derived approximate drop profiles, and conservation of mass. The model is analytical, and the results are presented in a dimensionless form. The effects of the temperature gradient, surface tension coefficient to surface tension ratio, liquid viscosity, and static advancing and receding contact angles on migration dynamics are analyzed.


[Case of neuro-Behçet disease with homonymous quadrantanopsia due to an inflammatory lesion involving the lateral geniculate body].
We report a rare case of a 57-year-old woman of neuro-Behçet disease with homonymous quadrantanopsia due to an inflammatory lesion involving the lateral geniculate body. She had oral and genital ulcers since 1983, and uveitis since May 1985. She received diagnosis of incomplete Behçet disease and was prescribed cyclophosphamide since June 1985. After the treatment, she recovered completely from uveitis in July 1985. Painful subcutaneous nodules appeared in her right leg on June 21, 2004 and she had a high fever, headache and left visual disturbance on June 29, 2004. Therefore, she was admitted to our hospital on July 1, 2004. Physical and neurological examination showed erythema nodosum in the right lower extremity and left lower homonymous quadrantanopsia. Laboratory findings on admission showed leucocytosis, increased erythrocyte sedimentation rate and C-reactive protein, and positive HLA-B51. Cerebrospinal fluid analysis showed pleocytosis and a markedly high level of protein and interleukin-6. Brain magnetic resonance imaging (MRI) of T2-weighted images showed high intensity lesions in the circumference of the caudal thalamus, optic radiations, and right occipital cortex. T1-weighted images with gadolinium enhancement showed an enhanced lesion in the circumference of the right lateral geniculate body. From these results, she was diagnosed as having an acute relapsing phase of neuro-Behçet disease and she received steroid pulse therapy. Immediately after steroid pulse therapy, she received high-dose prednisolone which was gradually tapered. Brain MRI after treatment showed a high intensity lesion in the right lateral geniculate body. Homonymous quadrantanopsia remained nearly unchanged.


Gas-Producing Infections in the Foot at a Large Academic Medical Center: A 10-Year Retrospective Review.
Gas-producing infections, such as clostridial and nonclostridial gas gangrene, crepitant cellulitis, and necrotizing fasciitis, are characterized in the literature by a variety of initial presentations, microbial burdens and surgical outcomes-ranging from debridement to amputation to death. The primary aim of this study was to identify the organisms cultured in gas-producing infections of the foot in patients that presented to a large academic medical center over a 10-year period. Our secondary aims were to report the prevalence of sepsis in this population upon presentation, and patient outcomes upon discharge. After a retrospective chart review of 207,534 procedures, 70 surgical cases met inclusion criteria. The most common organisms that grew in operating room cultures were Staphylococcus aureus, Group B Beta Streptococcus, and Enterococcus species. Just over half of the population presented with sepsis. After an average of 2 or more operations, 64% of patients underwent amputation. One death occurred. Gas-producing infections, or "gas gangrene," are primarily polymicrobial infections, rarely due to Clostridium perfringens, that warrant surgical exploration for optimal outcomes.


Physiology, phylogeny, and LUCA.
Genomes record their own history. But if we want to look all the way back to life's beginnings some 4 billion years ago, the record of microbial evolution that is preserved in prokaryotic genomes is not easy to read. Microbiology has a lot in common with geology in that regard. Geologists know that plate tectonics and erosion have erased much of the geological record, with ancient rocks being truly rare. The same is true of microbes. Lateral gene transfer (LGT) and sequence divergence have erased much of the evolutionary record that was once written in genomes, and it is not obvious which genes among sequenced genomes are genuinely ancient. Which genes trace to the last universal ancestor, LUCA? The classical approach has been to look for genes that are universally distributed. Another approach is to make all trees for all genes, and sift out the trees where signals have been overwritten by LGT. What is left ought to be ancient. If we do that, what do we find?


SNX17 regulates Notch pathway and pancreas development through the retromer-dependent recycling of Jag1.
Notch is one of the most important signaling pathways involved in cell fate determination. Activation of the Notch pathway requires the binding of a membrane-bound ligand to the Notch receptor in the adjacent cell which induces proteolytic cleavages and the activation of the receptor. A unique feature of the Notch signaling is that processes such as modification, endocytosis or recycling of the ligand have been reported to play critical roles during Notch signaling, however, the underlying molecular mechanism appears context-dependent and often controversial. Here we identified SNX17 as a novel regulator of the Notch pathway. SNX17 is a sorting nexin family protein implicated in vesicular trafficking and we find it is specifically required in the ligand-expressing cells for Notch signaling. Mechanistically, SNX17 regulates the protein level of Jag1a on plasma membrane by binding to Jag1a and facilitating the retromer-dependent recycling of the ligand. In zebrafish, inhibition of this SNX17-mediated Notch signaling pathway results in defects in neurogenesis as well as pancreas development. Our results reveal that SNX17, by acting as a cargo-specific adaptor, promotes the retromer dependent recycling of Jag1a and Notch signaling and this pathway is involved in cell fate determination during zebrafish neurogenesis and pancreas development.


Effects of crowding and sex on fecal cortisol levels of captive forest musk deer.
Restricted space and close contact with conspecifics in captivity may be stressful for musk deer, as they are highly territorial and solitary in the wild. So we tested the effects of crowding on stress of forest musk deer (Moschus berezovskii) in heterosexual groups, using fecal cortisol analysis as a non-invasive method. 32 healthy adults during non-breeding seasons were chose as our experimental objects. Group 1 was defined as higher crowding condition, with 10-15 m2/deer (6 enclosures, 10♀ and 6♂); group 2 was defined as lower crowding condition, with 23-33 m2/deer (6 enclosures, 10♀ and 6♂). Every enclosure contained 1 male and 3 female. These patterns had been existed for years. The results showed that females in lower crowding condition (217.1 ± 9.5 ug/g) had significantly higher fecal cortisol levels than those in higher crowding condition (177.2 ± 12.1 ug/g). Interestingly, crowding seemed have no effect on male fecal cortisol levels (148.1 ± 9.1 ug/g and 140.5 ± 13.3 ug/g, respectively). At both groups, cortisol was significantly lower in males than in females. These results showed that chronic crowding may affect stress status of captive forest musk deer. The captive environment should consider the space need for musk deer.


Phylogenetic analysis of trophic niche evolution reveals a latitudinal herbivory gradient in Clupeoidei (herrings, anchovies, and allies).
Biotic and abiotic forces govern the evolution of trophic niches, which profoundly impact ecological and evolutionary processes and aspects of species biology. Herbivory is a particularly interesting trophic niche because there are theorized trade-offs associated with diets comprised of low quality food that might prevent the evolution of herbivory in certain environments. Herbivory has also been identified as a potential evolutionary "dead-end" that hinders subsequent trophic diversification. For this study we investigated trophic niche evolution in Clupeoidei (anchovies, sardines, herrings, and their relatives) and tested the hypotheses that herbivory is negatively correlated with salinity and latitude using a novel, time-calibrated molecular phylogeny, trophic guilds delimited using diet data and cluster analysis, and standard and phylogenetically-informed statistical methods. We identified eight clupeoid trophic guilds: molluscivore, terrestrial invertivore, phytoplanktivore, macroalgivore, detritivore, piscivore, crustacivore, and zooplanktivore. Standard statistical methods found a significant negative correlation between latitude and the proportion of herbivorous clupeoids (herbivorous clupeoid species/total clupeoid species), but no significant difference in the proportion of herbivorous clupeoids between freshwater and marine environments. Phylogenetic least squares regression did not identify significant negative correlations between latitude and herbivory or salinity and herbivory. In clupeoids there were five evolutionary transitions from non-herbivore to herbivore guilds and no transitions from herbivore to non-herbivore guilds. There were no transitions to zooplanktivore, the most common guild, but it gave rise to all trophic guilds, except algivore, at least once. Transitions to herbivory comprised a significantly greater proportion of diet transitions in tropical and subtropical (<35°) relative to temperate areas (>35°). Our findings suggest cold temperatures may constrain the evolution of herbivory and that herbivory might act as an evolutionary "dead-end" that hinders subsequent trophic diversification, while zooplanktivory acts as an evolutionary "cradle" that facilitates trophic diversification.


Treatment Outcomes in Chronic Rhinosinusitis Refractory to Maximal Medical Therapy: A Prospective Observational Study Under Real-World Conditions.
This investigation explored the outcomes of 4 standardized treatments in patients with refractory chronic rhinosinusitis (CRS), despite recent maximal medical therapy (MMT). In a prospective observational study, we compared continued nasal steroids and irrigation (cNSI), repeated MMT (rMMT), pulsed nasal steroid inhalation (PSI), and endoscopic sinus surgery (ESS). Between November 2015 and March 2016, patients with symptomatic CRS despite having received MMT during the year prior to symptom reoccurrence were offered 1 of 4 standardized treatments. Reflecting real-world conditions, patients selected their treatment option following physician counseling. Sino-Nasal Outcome Test-22 (SNOT-22) scores were obtained before treatment, at the end of treatment, and at 2 months and 1 year following treatment. The mean (± standard deviation [SD]) duration since last MMT was 144 (±36 days). Of the 130 patients, 52 selected cNSI, 16 PSI, 19 rMMT, and 43 ESS. Mean SNOT-22 scores before treatment did not significantly differ between treatments (P = .99). Overall, SNOT-22 scores decreased from 38 ± 2 before treatment to 20 ± 2 after 1 year (P < .001), with a higher reduction for patients having CRS with nasal polyps than for those without nasal polyps (35 ± 2 to 15 ± 2 vs 41 ± 3 to 25 ± 4, respectively; both P < .001). Overall, no difference between the 3 medical treatments was observed (all P > .2). Post-treatment scores following ESS (19 ± 2) were significantly lower than for each of the 3 medical treatments (cNSI 26 ± 2, P = .004; PSI 27 ± 3, P = .026; rMMT 28 ± 3, P = .008). At 1 year following ESS, 26 of 31 patients were asymptomatic and did not require additional systemic steroids, compared to 25 of 50 patients following medical treatment (P = .002). The investigated standardized treatments significantly improved SNOT-22 scores in patients with refractory CRS under real-world conditions. Both patients having CRS with and those without nasal polyps showed significant improvement in SNOT-22 scores, although a less profound effect was found among the latter group. Patients who selected ESS were less symptomatic during the first follow-up year than patients who selected medical treatment alone. Patients with refractory CRS did not benefit from an additional course of MMT in comparison to those who were treated only with cNSI.


Deterioration of pituitary function without relapse after steroid therapy for IgG4-related hypophysitis.
IgG4-related hypophysitis is an autoimmune hypophysitis associated with IgG4-related disease. Swelling of the pituitary gland is responsive to steroid therapy, but the prognosis of pituitary function after the treatment remains unclear. The present case implies that transiently improved pituitary function can re-worsen during long-term follow-up in IgG4-related hypophysitis. A 71-year-old male patient with IgG4-related hypophysitis visited a nearby hospital with malaise, anorexia, and polyuria. Pituitary dysfunction was suspected, so he was referred to our hospital for further examination. Imaging studies and laboratory data showed swelling of the pituitary gland and panhypopituitarism, which dramatically improved following steroid therapy. There was no evidence of relapsing IgG4-related disease during prednisolone tapering. Pituitary function was examined after 4 years under treatment with low-dose prednisolone; surprisingly, anterior pituitary function had worsened again. Our case suggests a need for continuous monitoring of pituitary function after steroid therapy for IgG4-related hypophysitis. This report illustrates the natural course of pituitary function in IgG4-related hypophysitis and may be informative when considering the introduction of steroid therapy. Steroid therapy is an effective first-line therapy for pituitary dysfunction and pituitary swelling in IgG4-related hypophysitis. Pituitary function can worsen again during follow-up, despite transient improvement after steroid therapy in IgG4-related hypophysitis. Continuous monitoring of pituitary function is necessary for IgG4-related hypophysitis, regardless of disease activity.


Acetaminophen-induced anaphylaxis: a case report.
Acetaminophen is known to be generally safe, and the occurrence of anaphylaxis due to acetaminophen has been rarely reported. We report a case of acetaminophen-induced anaphylaxis in a healthy male subject who participated in a clinical trial on the pharmacokinetics of ibandronate. The subject had not experienced an allergic reaction to acetaminophen prior to this incident. The patient received 1300 mg oral acetaminophen at about 12 hours after receiving 150 mg ibandronate. After about 10 minutes, the subject developed whole-body urticaria and hypotension. The temporal association suggested that the anaphylaxis was due to acetaminophen and not ibandronate. Anaphylaxis could occur due to acetaminophen even in the absence of allergic reactions in the first dosing.


Adjunctive Application of Antimicrobial Photodynamic Therapy in Nonsurgical Periodontal Treatment: A Review of Literature.
Periodontal disease is caused by dental plaque biofilms, and the removal of these biofilms from the root surface of teeth plays a central part in its treatment. The conventional treatment for periodontal disease fails to remove periodontal infection in a subset of cases, such as those with complicated root morphology. Adjunctive antimicrobial photodynamic therapy (aPDT) has been proposed as an additional treatment for this infectious disease. Many periodontal pathogenic bacteria are susceptible to low-power lasers in the presence of dyes, such as methylene blue, toluidine blue O, malachite green, and indocyanine green. aPDT uses these light-activated photosensitizer that is incorporated selectively by bacteria and absorbs a low-power laser/light with an appropriate wavelength to induce singlet oxygen and free radicals, which are toxic to bacteria. While this technique has been evaluated by many clinical studies, some systematic reviews and meta-analyses have reported controversial results about the benefits of aPDT for periodontal treatment. In the light of these previous reports, the aim of this review is to provide comprehensive information about aPDT and help extend knowledge of advanced laser therapy.


Self-relevant beauty evaluation: Evidence from an event-related potentials study.
This study examines the electrophysiological correlates of beauty evaluation when participants performed the self-reference task. About 13 (7 men, 6 women) undergraduates participated in the experiment using event-related potentials. Results showed that the response to self-relevant information was faster compared to other-relevant information and no significant differences for self-relevant relative to mother-relevant information were observed. Both physical and interior beauty words for self-relevant information showed an enhanced late positive component as compared to other-relevant information. Physical beauty for self-relevant information yielded a larger late positive component in contrast to mother-relevant information but not for interior beauty. This study indicates that beauty is specific to the person who judges it though an individual and one's mother may hold similar views of interior beauty.


Measuring health workers' motivation composition: validation of a scale based on Self-Determination Theory in Burkina Faso.
Although motivation of health workers in low- and middle-income countries (LMICs) has become a topic of increasing interest by policy makers and researchers in recent years, many aspects are not well understood to date. This is partly due to a lack of appropriate measurement instruments. This article presents evidence on the construct validity of a psychometric scale developed to measure motivation composition, i.e., the extent to which motivation of different origin within and outside of a person contributes to their overall work motivation. It is theoretically grounded in Self-Determination Theory (SDT). We conducted a cross-sectional survey of 1142 nurses in 522 government health facilities in 24 districts of Burkina Faso. We assessed the scale's validity in a confirmatory factor analysis framework, investigating whether the scale measures what it was intended to measure (content, structural, and convergent/discriminant validity) and whether it does so equally well across health worker subgroups (measurement invariance). Our results show that the scale measures a slightly modified version of the SDT continuum of motivation well. Measurements were overall comparable between subgroups, but results indicate that caution is warranted if a comparison of motivation scores between groups is the focus of analysis. The scale is a valuable addition to the repository of measurement tools for health worker motivation in LMICs. We expect it to prove useful in the quest for a more comprehensive understanding of motivation as well as of the effects and potential side effects of interventions intended to enhance motivation.


Accuracy of Electronic Health Record Data for Identifying Stroke Cases in Large-Scale Epidemiological Studies: A Systematic Review from the UK Biobank Stroke Outcomes Group.
Long-term follow-up of population-based prospective studies is often achieved through linkages to coded regional or national health care data. Our knowledge of the accuracy of such data is incomplete. To inform methods for identifying stroke cases in UK Biobank (a prospective study of 503,000 UK adults recruited in middle-age), we systematically evaluated the accuracy of these data for stroke and its main pathological types (ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage), determining the optimum codes for case identification. We sought studies published from 1990-November 2013, which compared coded data from death certificates, hospital admissions or primary care with a reference standard for stroke or its pathological types. We extracted information on a range of study characteristics and assessed study quality with the Quality Assessment of Diagnostic Studies tool (QUADAS-2). To assess accuracy, we extracted data on positive predictive values (PPV) and-where available-on sensitivity, specificity, and negative predictive values (NPV). 37 of 39 eligible studies assessed accuracy of International Classification of Diseases (ICD)-coded hospital or death certificate data. They varied widely in their settings, methods, reporting, quality, and in the choice and accuracy of codes. Although PPVs for stroke and its pathological types ranged from 6-97%, appropriately selected, stroke-specific codes (rather than broad cerebrovascular codes) consistently produced PPVs >70%, and in several studies >90%. The few studies with data on sensitivity, specificity and NPV showed higher sensitivity of hospital versus death certificate data for stroke, with specificity and NPV consistently >96%. Few studies assessed either primary care data or combinations of data sources. Particular stroke-specific codes can yield high PPVs (>90%) for stroke/stroke types. Inclusion of primary care data and combining data sources should improve accuracy in large epidemiological studies, but there is limited published information about these strategies.


Palladium-catalyzed carbonylative Sonogashira coupling of aryl bromides via tert-butyl isocyanide insertion.
A simple and efficient palladium-catalyzed carbonylative Sonogashira coupling via tert-butyl isocyanide insertion has been developed, which demonstrates the utility of isocyanides in intermolecular C-C bond construction. This methodology provides a novel pathway for the synthesis of alkynyl imines which can undergo simple silica gel catalyzed hydrolysis to afford alkynones. The approach is tolerant of a wide range of substrates and applicable to library synthesis.


The contribution of omental adipose tissue to adipokine concentrations in patients with the metabolic syndrome.
To examine differences in peripheral vascular endothelial growth factor (VEGF), interleukin-6 (IL6) and cortisol concentrations between patients with both visceral obesity and metabolic syndrome, and lean controls. In a subsample of metabolic patients underwent abdominal surgery, the adipokine concentrations were measured in venous blood from the omentum to determine information on some processes of synthesis. Forty-two healthy lean controls and 46 overweight-obese patients with central adiposity and stigmata of metabolic syndrome were studied. In a subsample of 11 metabolic patients undergoing non-bariatric surgery, blood samples from omental and peripheral veins were taken intraoperatively to determine VEGF, IL6 and cortisol concentrations. Median levels (range) of peripheral VEGF and IL6 were higher in patients than in controls [31.5 (3-112) pg/mL vs 21.35 (9-41.9) pg/mL (P < 0.05) and 5.50 (1.40-13) pg/mL vs 1.15 (0.3-1) pg/mL (P < 0.0001)]. On the other hand, concentrations of VEGF and IL6 from the omental and peripheral veins were similar in the surgery sub-group. Peripheral cortisol concentrations were not higher in patients than in controls, nor were omental concentrations different from the peripheral. Omental and peripheral VEGF and cortisol values were correlated, whereas no association was found between omental and peripheral IL6. In the presence of abdominal obesity, VEGF and IL6 concentrations are increased in the systemic circulation. The contribution of visceral adipose tissue to circulating levels of VEGF and IL6 was modest.


Effect of low dose methotrexate on neutrophil chemotaxis induced by leukotriene B4 and complement C5a.
When mediators of inflammation such as complement component C5a or leukotriene B4 are introduced into an air pouch created in mice, these mediators induce the migration of neutrophils into the air pouch. Pretreatment of mice with low doses of methotrexate inhibits leukotriene B4 or C5a induced neutrophil migration into the air pouch. Inhibition of neutrophil chemotaxis by methotrexate may, at least in part, account for the rapid onset of antiinflammatory activity that was observed in clinical trials with methotrexate in rheumatoid arthritis.


Ipsilesional motor area size correlates with functional recovery after stroke: a 6-month follow-up longitudinal TMS motor mapping study.
Transcranial magnetic stimulation (TMS) and measurements of upper limb function were longitudinally applied to gain further insights into processes involved in functional recovery from the acute to the chronic stage after stroke. 10 acute stroke patients were monitored over 6 months behaviourally and with established TMS protocols. By using neuronavigated motor mapping, behavioural parameters, and a mixed model analysis, the role of the frontal and parietal part of the motor area of both hemispheres for functional recovery was determined. Size and volume of the ipsilesional motor area (MAipsi) were significantly decreased in the acute phase compared to the contralesional motor area (MAcontra). Size of MAipsi, especially its frontal part, changed over time and was positively correlated with functional recovery, whereas resting motor threshold, volume of both MA or the shift of its center of gravity did not show any association with recovery. The present data suggests the presence of a positive correlation between changes of the motor representation of the lesioned hemisphere and functional recovery after stroke. A possible interpretation is that rather (re-)activated corticomotor outputs are substrates of functional recovery after stroke than increased efficacy of residual, non-lesioned pathways.


The Cpn10(1) co-chaperonin of A. thaliana functions only as a hetero-oligomer with Cpn20.
The A. thaliana genome encodes five co-chaperonin homologs, three of which are destined to the chloroplast. Two of the proteins, Cpn10(2) and Cpn20, form functional homo-oligomers in vitro. In the current work, we present data on the structure and function of the third A. thaliana co-chaperonin, which exhibits unique properties. We found that purified recombinant Cpn10(1) forms inactive dimers in solution, in contrast to the active heptamers that are formed by canonical Cpn10s. Additionally, our data demonstrate that Cpn10(1) is capable of assembling into active hetero-oligomers together with Cpn20. This finding was reinforced by the formation of active co-chaperonin species upon mixing an inactive Cpn20 mutant with the inactive Cpn10(1). The present study constitutes the first report of a higher plant Cpn10 subunit that is able to function only upon formation of hetero-oligomers with other co-chaperonins.


Treatment of advanced differentiated thyroid carcinoma with high activity radioiodine therapy.
This was a retrospective study to assess the efficacy and morbidity of high activity I therapy in patients with advanced differentiated thyroid carcinoma. From 1975 to 2003, 38 patients with locally advanced or metastatic differentiated thyroid cancer (16 follicular, 20 papillary, one Hurthle cell, one insular) were treated with high activity radioiodine therapy (9 GBq) as the cancers had previously not responded to standard activities (5.5 GBq). Cumulative total activities received ranged from 11.8 to 84.5 GBq (mean 29.4 GBq per patient). Staging at presentation showed pT4 and/or M1 disease in 27/38 of patients (71.1%). Moderate (grade 2) and poorly differentiated (grade 3) tumours were present in a total of 9/38 patients (23.7%). Outcomes were evaluated according to the results of I whole-body scans, serum thyroglobulin, radiological assessments and physical examination. Neither [18F]flurodeoxyglucose positron emission tomography (F-FDG PET) nor 99mTc sestamibi were available during this study. The mean duration of follow-up was 83 months. A complete response was observed in 7/38 patients (18.4%), progressive disease in 27/38 (71.1%) and stable disease in 4/38 (10.5%). The mean survival from initiation of high activity treatment was 36.6 months. For patients with lung disease the mean survival was 45 months, neck disease 38.9 months, bone disease 35 months and multiple sites was 30.9 months. Twelve patients died during follow-up (10 due to thyroid carcinoma). After high activity treatment, 9.7% of patients suffered grade 3 and 3.2% suffered grade 4 WHO haematological toxicity. Significant salivary gland morbidity was observed (30% dry mouth, 27% salivary swelling). Repeated treatment with high activity (9 GBq) I in patients with advanced differentiated thyroid carcinoma appears to be of no apparent benefit and may lead to late morbidity.


Ultrastructural changes of the tracheal epithelium after vaccination of day-old chickens with the La Sota strain of Newcastle disease virus.
The progression of tracheal lesions induced by vaccination of day-old specific pathogen-free chicks with the La Sota strain of Newcastle disease virus (NDV) was examined by relating surface changes as observed by scanning electron microscopy with subcellular changes seen by transmission electron microscopy. NDV infection resulted in hypertrophy of goblet cells, their rupture, and the formation of excess mucus. Activation of goblet cells peaked within 4 days postvaccination. Afterward, the activation levels gradually decreased. At the level of the ciliated cells, a marked increase in the proportion of nonciliated to ciliated cells and later an almost complete deciliation of the tracheal surface were observed because a simple squamous to cuboidal epithelium replaced the original pseudostratified epithelium. Fifteen days postvaccination, all epithelial damage was restored. Because the observed vaccination-induced lesions are detrimental to epithelial integrity and function as a barrier against invading microorganisms, they might explain at the ultrastructural level the secondary complications of vaccination with the La Sota strain against NDV.


Optimization of In Vitro Germination, Viability Tests and Storage of Paeonia ostii Pollen.
Paeonia ostii is an important woody oil crop mainly cross-pollinated. However, the low yield has become an important factor restricting the industrial development of P. ostii. Cross-pollination has become one of the important measures to increase the seed yield. Therefore, conservation of pollen with high vitality is crucial to ensure successful pollination of P. ostii. In this study, we found an effective methodological system to assess the viability, ability to germinate, and optimal storage conditions of P. ostii pollen grains. The optimal medium in vitro was 50 g/L sucrose, 100 mg/L boric acid, 50 g/L PEG6000, 100 mg/L potassium nitrate, 300 mg/L calcium nitrate, and 200 mg/L magnesium sulfate at pH 5.4. Optimal germination condition in vitro was achieved at 25 °C for 120 min, allowing easy observation of the germination percentage and length of the pollen tubes. In addition, the viability of pollen grains was assessed by comparing nine staining methods. Among them, MTT, TTC, benzidine-H2O2, and FDA were effective to distinguish between viable and non-viable pollen, and the results of the FDA staining method were similar to the pollen germination percentage in vitro. After evaluation of pollen storage, thawing and rehydration experiments showed that thawing at 4 °C for 30 min and rehydration at 25 °C for 30 min increased the germination percentage of pollen grains stored at low temperatures. The low-temperature storage experiments showed that 4 °C was suitable for short-term storage of P. ostii pollen grains, while -80 °C was suitable for long-term storage. This is the first report on the in vitro germination, viability tests, and storage of P. ostii pollen grains, which will provide useful information for P. ostii germplasm conservation and artificial pollination.


Progesterone-stimulated intracellular calcium increase in human spermatozoa is protein kinase C-independent.
Indirect studies suggested that protein kinase C (PKC) has a role in sperm motility and the acrosome reaction. Physiological inducers of the sperm acrosome reaction include progesterone, which can increase intracellular calcium ([Ca2+]i), tyrosine phosphorylation of proteins and chloride efflux in human spermatozoa. PKC may be involved in progesterone-stimulated acrosome reaction, although controversial results have been obtained concerning the effect of PKC inhibition on progesterone-stimulated [Ca2+]i increase. In the present study, we investigated the direct effect of progesterone on the activity of PKC, as well as the effect of a panel of PKC inhibitors on progesterone-stimulated [Ca2+]i increase and tyrosine phosphorylation of proteins. We found that progesterone stimulates sperm PKC activity and that PKC inhibition with staurosporine and bisindolylmaleimide partially reversed the effect of progesterone on acrosome reaction, indicating an involvement of the enzyme in the effect of the steroid. We next evaluated the effect of three different PKC inhibitors (sangivamycin, staurosporine and bisindolylmaleimide) on progesterone-stimulated [Ca2+]i increase. Neither short-term (15 min) nor long-term (90 min) preincubation with any of the three compounds had a substantial effect on the stimulatory effect of progesterone on sperm [Ca2+]i. Nor was responsiveness to progesterone affected by either short-term (determining activation of PKC) or long-term (determining down-regulation of PKC) incubation with the tumour promoter phorbol myristate acetate (PMA), a known non-physiological stimulator of PKC. These results indicate that progesterone-stimulated calcium influx is independent of PKC activation. In addition, we found that preincubation with PKC inhibitors had a stimulatory effect per se on tyrosine phosphorylation of sperm proteins. When compared with the appropriate control, the effect of progesterone on tyrosine phosphorylation was slightly (but not significantly) reduced by the inhibitors, sangivamycin, staurosporine and bisindolylmaleimide, but was significantly inhibited by calphostin C. These results do not permit a final conclusion on the involvement of PKC in progesterone-stimulated tyrosine phosphorylation of sperm proteins. However, the lack of effect of PMA on tyrosine phosphorylation indicates that PKC stimulation is not sufficient to induce this effect. In conclusion, our results indicate that PKC plays a role in progesterone-induced acrosome reaction and that progesterone-stimulated PKC activation is downstream to stimulation of calcium influx by the steroid.


Role of TLR3 in the immunogenicity of replicon plasmid-based vaccines.
Replicon plasmids encoding an alphavirus RNA replicase constitute an alternative to conventional DNA plasmids with promise for DNA vaccination in humans. Replicase activity amplifies the levels of transgene mRNA through a copying process involving double-stranded (ds) RNA intermediates, which contribute to vaccine immunogenicity by activating innate antiviral responses. Toll-like receptor 3 (TLR3) is a dsRNA innate immune receptor expressed by antigen-presenting dendritic cells (DCs). Here, we test the hypothesis that TLR3 is necessary for the immunogenicity of replicon plasmid-based DNA vaccines. We show that mouse CD8 alpha(+) DC phagocytose dying replicon plasmid-transfected cells in vitro and are activated in a TLR3-dependent manner by dsRNA present within those cells. However, we find that cytotoxic T-cell responses to a replicon plasmid intramuscular vaccine are not diminished in the absence of TLR3 in vivo. Our results underscore the potential role of TLR3 in mediating immune activation by dsRNA-bearing replicon plasmid-transfected cells and indicate that other innate sensing pathways can compensate for TLR3 absence in vivo.


Toward High-Performance Vacuum-Deposited OLEDs: Sublimable Cationic Iridium(III) Complexes with Yellow and Orange Electroluminescence.
Great advances in the development of efficient luminescent materials are the driving force behind organic light-emitting diodes (OLEDs). Sublimable ionic transition-metal complexes (iTMCs) have emerged as a large family of new emissive dopants applied for vacuum-deposited OLEDs, while the achievement of excellent performance remains arduous. A series of novel sublimable cationic iridium(III) complexes have been designed and synthesized, containing an imidazole-type ancillary ligand and tetraphenylborate-type negative counter-ions with large steric hindrance and well-dispersed charges. The photophysical properties, electrochemical behaviors, and thermal stability are fully investigated and discussed, then demonstrated by theoretical calculations. Yellow- and orange-emitting OLEDs thereof are fabricated by vacuum evaporation deposition, realizing a high external quantum efficiency of up to 11 %, maximum brightness over 27.3×103 cd m-2 and low turn-on voltages below 2.4 V, among the best results of analogous phosphorescent OLEDs based on iTMCs. This work indicates the promising applications of sublimable iTMCs in state-of-the-art vacuum-deposited optoelectronic devices.


Coronary heart disease in women: evaluation and management.
Coronary heart disease should not be considered a male dominated disease. The incidence of clinical CHD lags by several years in women, but it remains a leading cause of death and disability in the adult female. Risk factors for the development of coronary atherosclerosis are essentially the same for both sexes. Management strategies are usually similar regardless of gender.


[Efficacy and safety of a herbal drug containing hawthorn berries and D-camphor in hypotension and orthostatic circulatory disorders/results of a retrospective epidemiologic cohort study].
Korodin Herz-Kreislauf-Tropfen, a herbal drug containing D-camphor (CAS 76-22-2; 2.5 %) and a liquid extract of fresh hawthorn berries (97.3%), has been used since many years for the treatment of orthostatic hypotension. The combination as well as its constituents were tested in clinical trials against placebo with healthy volunteers and patients using tilt-tests. The objective of this study was to investigate efficacy and safety of the drug under the conditions of medical practice in comparison to other drugs admitted for this indication. The study was performed as an epidemiological retrospective cohort study in 46 medical practices in Germany. In the practices the files were reviewed for patients who were treated between 1st January 2000 and 31st December 2002 for orthostatic hypotension. Included in the study were all patients who were treated either with the test drug or a control drug containing etilefrine, oxilofrine, midodrine, norfenefrine or dihydroergotamine and who met the inclusion criteria. The data of the files were coded, transferred to case report forms and augmented by the physician's statements about symptoms and success. Effect criteria were the improvement of symptoms and change of blood pressure during treatment. The correctness of the data was controlled using anonymous copies of the files. A total of 490 patients (399 in the test-group and 91 in the control group) between 11 and 102 years were included in the study. To correct heterogeneities in baseline conditions, treatment results were adjusted by regression and stratification to equal baseline conditions using the propensity score. The adjusted odds ratio for improvement was 5.6, the adjusted mean increase of the systolic blood pressure the 2-fold compared to the control group. The difference was highly significant and did not depend on age or initial blood pressure. In the test group two adverse events were observed which had no relation to the medication; in the control group one reversible event with a probable relation to the medication was observed. The test drug was proven as effective and safe in the treatment of orthostatic hypotension in medical practice for all age groups and independent of the initial blood pressures.


Biologic rhythms derived from Siberian mammoths' hairs.
Hair is preserved for millennia in permafrost; it enshrines a record of biologic rhythms and offers a glimpse at chronobiology as it was in extinct animals. Here we compare biologic rhythms gleaned from mammoth's hairs with those of modern human hair. Four mammoths' hairs came from varying locations in Siberia 4600 km, four time zones, apart ranging in age between 18,000 and 20,000 years before present. We used two contemporaneous human hairs for comparison. Power spectra derived from hydrogen isotope ratios along the length of the hairs gave insight into biologic rhythms, which were different in the mammoths depending on location and differed from humans. Hair growth for mammoths was ∼31 cms/year and ∼16 cms/year for humans. Recurrent annual rhythms of slow and fast growth varying from 3.4 weeks/cycles to 8.7 weeks/cycles for slow periods and 1.2 weeks/cycles to 2.2 weeks/cycles for fast periods were identified in mammoth's hairs. The mineral content of mammoth's hairs was measured by electron microprobe analysis (k-ratios), which showed no differences in sulfur amongst the mammoth hairs but significantly more iron then in human hair. The fractal nature of the data derived from the hairs became evident in Mandelbrot sets derived from hydrogen isotope ratios, mineral content and geographic location. Confocal microscopy and scanning electron microscopy showed varied degrees of preservation of the cuticle largely independent of age but not location of the specimens. X-ray fluorescence microprobe and fluorescence computed micro-tomography analyses allowed evaluation of metal distribution and visualization of hollow tubes in the mammoth's hairs. Seasonal variations in iron and copper content combined with spectral analyses gave insights into variation in food intake of the animals. Biologic rhythms gleaned from power spectral plots obtained by modern methods revealed life style and behavior of extinct mega-fauna.


Auger electron spectroscopy: a rational method for determining thickness of graphene films.
We report the determination of the thickness of graphene layers by Auger electron spectroscopy (AES). We measure AES spectra of graphenes with different numbers of layers. The AES spectroscopy shows distinct spectrum shape, intensity, and energy characteristics with an increasing number of graphene layers. We also calculate electron inelastic mean free paths for graphene layers directly from these measurements. The method allows unambiguous and high-throughput determination of thickness up to six graphene layers and detection of defect and dopant in graphene films on almost any substrate. The availability of this reliable method will permit direct probing of graphene growth mechanisms and exploration of novel properties of graphenes with different thicknesses on diverse substrates.


Two-year stability of the late positive potential across middle childhood and adolescence.
The late positive potential (LPP) may be a useful measure of individual differences in emotional processing across development, but little is known about the stability of the LPP across time. We assessed the LPP and behavioral measures of emotional interference following pleasant, unpleasant, and neutral images in 8- to 13-year-old youth. Approximately two years later, the same participants completed the task again (N=34). Results indicated that the LPP is moderately-to-highly reliable across development. Stability was lower and more inconsistent for behavioral measures. In addition, consistent with previous cross-sectional analyses, a decrease in occipital activity was observed at the second assessment. Results indicate that the LPP appears to be a stable measure of emotional processing, even across a fairly large period of development.


Biology of the heat shock response and protein chaperones: budding yeast (Saccharomyces cerevisiae) as a model system.
The eukaryotic heat shock response is an ancient and highly conserved transcriptional program that results in the immediate synthesis of a battery of cytoprotective genes in the presence of thermal and other environmental stresses. Many of these genes encode molecular chaperones, powerful protein remodelers with the capacity to shield, fold, or unfold substrates in a context-dependent manner. The budding yeast Saccharomyces cerevisiae continues to be an invaluable model for driving the discovery of regulatory features of this fundamental stress response. In addition, budding yeast has been an outstanding model system to elucidate the cell biology of protein chaperones and their organization into functional networks. In this review, we evaluate our understanding of the multifaceted response to heat shock. In addition, the chaperone complement of the cytosol is compared to those of mitochondria and the endoplasmic reticulum, organelles with their own unique protein homeostasis milieus. Finally, we examine recent advances in the understanding of the roles of protein chaperones and the heat shock response in pathogenic fungi, which is being accelerated by the wealth of information gained for budding yeast.


Pelvic intraoperative iatrogenic oncosurgical injuries: single-center experience.
Iatrogenic events are more likely to occur during surgical treatment of malignant conditions. Gynecologic and colorectal cancers account for most of the cases that require surgical treatment within the pelvic area. The purpose of this study was to analyze the incidence of intraoperative accidents and the most frequently encountered injuries during surgery for cancers of the pelvic area. The records of 2702 patients admitted to our clinic over a 15-year period, (January 2000-December 2014), were analyzed for type and frequency of intraoperative accidents. Urinary tract lesions were the most common injuries seen in this series (63.1%), followed by enteral (28.1%) and vascular (8.8%) injuries, with an overall incidence of 2.9% for the whole group. Iatrogenic injuries showed a statistically significant difference in incidence depending on the type of primary malignancy (p<0.002). Cervical cancer was associated with a higher rate of ureteral lesions, whereas enteral injuries occurred predominantly during surgical resection for ovarian cancer. The use of neoadjuvant radiotherapy or chemotherapy has been associated with a significantly lower risk of surgical iatrogenic injuries (p=0.004). Immediate recognition of the lesion and prompt treatment are recommended in order to lower postoperative complications and to avoid a second operation.


Effect of Duloxetine on Opioid Use and Pain After Total Knee Arthroplasty: A Triple-Blinded Randomized Controlled Trial.
Duloxetine, a serotonin-norepinephrine dual reuptake inhibitor, may improve analgesia after total knee arthroplasty (TKA). Previous studies had one primary outcome, did not consistently use multimodal analgesia, and used patient-controlled analgesia devices, potentially delaying discharge. We investigated whether duloxetine would reduce opioid consumption or pain with ambulation. A total of 160 patients received 60 mg duloxetine or placebo daily, starting from the day of surgery and continuing 14 days postoperatively. Patients received neuraxial anesthesia, peripheral nerve blocks, acetaminophen, nonsteroidal anti-inflammatory drugs, and oral opioids as needed. The dual primary outcomes were Numeric Rating Scale (NRS) scores with movement on postoperative days 1, 2, and 14, and cumulative opioid consumption surgery through postoperative day 14. Duloxetine was noninferior to placebo for both primary outcomes and was superior to placebo for opioid consumption. Opioid consumption (mean ± SD) was 288 ± 226 mg OME [94, 385] vs 432 ± 374 [210, 540] (duloxetine vs placebo) P = .0039. Pain scores on POD14 were 4.2 ± 2.0 vs 4.8 ± 2.2 (duloxetine vs placebo) P = .018. Median satisfaction with pain management was 10 (8, 10) and 8 (7, 10) (duloxetine vs placebo) P = .046. Duloxetine reduced interference by pain with walking, normal work, and sleep. The 29% reduction in opioid use corresponds to 17 fewer pills of oxycodone, 5 mg, and was achieved without increasing pain scores. Considering the ongoing opioid epidemic, duloxetine can be used to reduce opioid usage after knee arthroplasty in selected patients that can be appropriately monitored for potential side effects of the medication.


Inhibition of astrocyte glutamine production by alpha-ketoisocaproic acid.
We have evaluated the effect of alpha-ketoisocaproic acid (KIC), the ketoacid of leucine, on the production of glutamine by cultured astrocytes. We used 15NH4Cl as a metabolic tracer to measure the production of both [5-15N]glutamine, reflecting amidation of glutamate via glutamine synthetase, and [2-15N]glutamine, representing the reductive amination of 2-oxoglutarate via glutamate dehydrogenase and subsequent conversion of [15N]glutamate to [2-15N]glutamine. Addition of KIC (1 mM) to the medium diminished the production of [5-15N]glutamine and stimulated the formation of [2-15N]glutamine with the overall result being a significant inhibition of net glutamine synthesis. An external KIC concentration as low as 0.06 mM inhibited synthesis of [5-15N]glutamine and a level as low as 0.13 mM enhanced labeling (atom% excess) of [2-15N]glutamine. Higher concentrations of KIC in the medium had correspondingly larger effects. The presence of KIC in the medium did not affect flux through glutaminase, which was measured using [2-15N]glutamine as a tracer. Nor did KIC inhibit the activity of glutamine synthetase that was purified from sheep brain. Addition of KIC to the medium caused no increased release of lactate dehydrogenase from the astrocytes, suggesting that the ketoacid was not toxic to the cells. KIC treatment was associated with an approximately twofold increase in the formation of 14CO2 from [U-14C]glutamate, indicating that transamination of glutamate with KIC increases intraastrocytic alpha-ketoglutarate, which is oxidized in the tricarboxylic acid cycle. KIC inhibited glutamine synthesis more than any other ketoacid tested, with the exception of hydroxypyruvate.(ABSTRACT TRUNCATED AT 250 WORDS)


[Recent progress of aptasensors for tumor exosome-associated protein detection].
Exosomes are phospholipid bilayer membrane-enclosed vesicles released from cells with diameters of 30-150 nm, exosomes can directly reflect the physiological and functional state of secretory cells, participate in material transport and information communication between cells, which are of great significance as biomarkers for early tumor diagnosis and treatment evaluation. There are many detection methods for exosomes, among which aptasensor technology with the properties of low price and easy operation, fast response, high sensitivity, remarkable specificity helps tumor patients to find, diagnose and treat early, improve the survival rate, and provide important basis for the evaluation of the prognosis. There are seven types of common aptasensors: fluorescent, electrochemical, colorimetric, luminescence, lateral flow strips, surface-enhanced Raman scattering and surface plasmon resonance sensors. Different aptasensors have different characteristics, this article focuses on the research progress of several common aptasensor for tumor exosomes detection.


Origin of mounds in the Pantanal wetlands: An integrated approach between geomorphology, pedogenesis, ecology and soil micromorphology.
Vegetated mounds are an important geomorphological feature of the Pantanal, where the influence of floods dictates not only hydropedological processes, but also the distribution and ecology of the flora and fauna. This work aimed to identify factors and processes that influence the formation and spatial distribution of the mounds, which are commonly associated with termite activity. In order to characterize pedological processes, macro and micro morphological descriptions, satellite image interpretation, dating of the sandy sedimentary material using OSL and carbon dating using 14C AMS were carried out. This dating of the materials indicates that the sediments in which the soils were formed were deposited during the Pleistocene, while the carbonates are from the Holocene. The basin-like format of the laminar structures suggests that part of the more clayey material was deposited in lacustrine environments. The more humid climate in the Holocene intensified argilluviation, which at an advanced stage, led to a more pronounced textural gradient, reducing drainage and leading to ferrolysis and thickening of the E horizon. Besides pedogenic processes, more erosive flooding during the Holocene began reducing and rounding the landscape's more elevated structures (paleolevees). In the final stage, these structures were occupied by termites to shelter from flooding. Thereafter, the bio-cementation action of the termite nests has increased the resistance of the vegetated mounds to processes of erosion.


Fullerene Derivatives as Lung Cancer Cell Inhibitors: Investigation of Potential Descriptors Using QSAR Approaches.
Nanotechnology-based strategies in the treatment of cancer have potential advantages because of the favorable delivery of nanoparticles into tumors through porous vasculature. In the current study, we synthesized a series of water-soluble fullerene derivatives and observed their anti-tumor effects on human lung carcinoma A549 cell lines. The quantitative structure-activity relationship (QSAR) modeling was employed to investigate the relationship between anticancer effects and descriptors relevant to peculiarities of molecular structures of fullerene derivatives. In the QSAR regression model, the evaluation results revealed that the determination coefficient r2 and leave-one-out cross-validation q2 for the recommended QSAR model were 0.9966 and 0.9246, respectively, indicating the reliability of the results. The molecular modeling showed that the lack of chlorine atom and a lower number of aliphatic single bonds in saturated hydrocarbon chains may be positively correlated with the lung cancer cytotoxicity of fullerene derivatives. Synthesized water-soluble fullerene derivatives have potential functional groups to inhibit the proliferation of lung cancer cells. The guidelines obtained from the QSAR model might strongly facilitate the rational design of potential fullerene-based drug candidates for lung cancer therapy in the future.


Gene therapy for neurologic manifestations of mucopolysaccharidoses.
Mucopolysaccharidoses (MPS) are a family of lysosomal disorders caused by mutations in genes that encode enzymes involved in the catabolism of glycoaminoglycans. These mutations affect multiple organ systems and can be particularly deleterious to the nervous system. At the present time, enzyme replacement therapy and hematopoietic stem-cell therapy are used to treat patients with different forms of these disorders. However, to a great extent, the nervous system is not adequately responsive to current therapeutic approaches. Recent advances in gene therapy show great promise for treating MPS. This article reviews the current state of the art for routes of delivery in developing genetic therapies for treating the neurologic manifestations of MPS. Gene therapy for treating neurological manifestations of MPS can be achieved by intraventricular, intrathecal, intranasal and systemic administrations. The intraventricular route of administration appears to provide the most widespread distribution of gene therapy vectors to the brain. The intrathecal route of delivery results in predominant distribution to the caudal areas of the brain. The systemic route of delivery via intravenous infusion can also achieve widespread delivery to the CNS; however, the distribution to the brain is greatly dependent on the vector system. Intravenous delivery using lentiviral vectors appear to be less effective than adeno-associated viral (AAV) vectors. Moreover, some subtypes of AAV vectors are more effective than others in crossing the blood-brain barrier. In summary, the recent advances in gene vector technology and routes of delivery to the CNS will facilitate the clinical translation of gene therapy for the treatment of the neurological manifestations of MPS.


Extracellular matrix degradation pathways and fatty acid metabolism regulate distinct pulmonary vascular cell types in pulmonary arterial hypertension.
Pulmonary arterial hypertension describes a group of diseases characterised by raised pulmonary vascular resistance, resulting from vascular remodelling in the pre-capillary resistance arterioles. Left untreated, patients die from right heart failure. Pulmonary vascular remodelling involves all cell types but to date the precise roles of the different cells is unknown. This study investigated differences in basal gene expression between pulmonary arterial hypertension and controls using both human pulmonary microvascular endothelial cells and human pulmonary artery smooth muscle cells. Human pulmonary microvascular endothelial cells and human pulmonary artery smooth muscle cells from pulmonary arterial hypertension patients and controls were cultured to confluence, harvested and RNA extracted. Whole genome sequencing was performed and after transcript quantification and normalisation, we examined differentially expressed genes and applied gene set enrichment analysis to the differentially expressed genes to identify putative activated pathways. Human pulmonary microvascular endothelial cells displayed 1008 significant (p ≤ 0.0001) differentially expressed genes in pulmonary arterial hypertension samples compared to controls. In human pulmonary artery smooth muscle cells, there were 229 significant (p ≤ 0.0001) differentially expressed genes between pulmonary arterial hypertension and controls. Pathway analysis revealed distinctive differences: human pulmonary microvascular endothelial cells display down-regulation of extracellular matrix organisation, collagen formation and biosynthesis, focal- and cell-adhesion molecules suggesting severe endothelial barrier dysfunction and vascular permeability in pulmonary arterial hypertension pathogenesis. In contrast, pathways in human pulmonary artery smooth muscle cells were mainly up-regulated, including those for fatty acid metabolism, biosynthesis of unsaturated fatty acids, cell-cell and adherens junction interactions suggesting a more energy-driven proliferative phenotype. This suggests that the two cell types play different mechanistic roles in pulmonary arterial hypertension pathogenesis and further studies are required to fully elucidate the role each plays and the interactions between these cell types in vascular remodelling in disease progression.


[Fluoxetine enhances combined learning and memory abilities of mice by promoting neural cell functions in the barrel cortex].
To study the behavioral characteristics of memory maintenance and regression in a mouse model of combined learning and memory training with fluoxetine treatment and explore the neural basis for learning and memory in the barrel area of the brain. Twenty-six 16-day-old C57 mice were randomized into two equal groups and were given daily intraperitoneal injection of saline (control) or fluoxetine. The mice were subjected to stimulation of the right whiskers using a multi-sensory stimulation simulator and were given simultaneously olfactory stimulation with butyl acetate. In the initial 10 days of the experiment, the mice were given corresponding drug treatment followed by whisker and olfactory stimulations on a daily basis; from day 11 to day 17, only the drugs were administered without the stimulations; on day 18, both the drugs and stimulations were administered. The daily performance of the mice was recorded and analyzed. In the field potential experiment, the left barrel cortex of the mouse brain was selected to record the frequency of field potential signals in response to whisker stimulation. In the behavioral test, the mice treated with fluoxetine showed greater increments of the frequency and angle of whisker deflection than the control mice (P < 0.01). Compared with the peak levels that occurred on the 10th day, the swing angle and frequency of the whisker deflection decreased on the 17th day decreased in both groups, and the reduction was more obvious in the control group (P < 0.05). During the training on the 18th day, the whisker movement of the mice increased rapidly to the peak level and showed significant differences between the two groups (P < 0.05). In the field potential experiment on the 10th and 17th day, the frequencies of field potential signal in response to whisker stimulation was significantly higher in fluoxetine group than in the control group (P < 0.05). Combined training of the mice results in the formation of combined memory. Fluoxetine can enhance combined learning and memory abilities and prolong such memories in mice by promoting the function of the barrel cortex cells.


Local deformation for soft tissue simulation.
This paper presents a new methodology to localize the deformation range to improve the computational efficiency for soft tissue simulation. This methodology identifies the local deformation range from the stress distribution in soft tissues due to an external force. A stress estimation method is used based on elastic theory to estimate the stress in soft tissues according to a depth from the contact surface. The proposed methodology can be used with both mass-spring and finite element modeling approaches for soft tissue deformation. Experimental results show that the proposed methodology can improve the computational efficiency while maintaining the modeling realism.


A proportional hazards model with time-dependent covariates and time-varying effects for analysis of fetal and infant death.
Birth-weight- and gestational-age-specific perinatal mortality curves intersect when compared by race and maternal smoking. The authors propose a new measure to replace fetal and infant mortality and an analytic strategy to assess the effects of risk factors on this outcome. They used 1998 data for US Blacks and Whites. Age-specific post-last menstrual period (LMP) mortality rate was defined as the proportion of deaths (stillbirth, perinatal death, or infant death) at a given age post-LMP. The authors used extended Cox regression with time-varying covariates and hazard ratios to model the effects of race and smoking on post-LMP mortality. Perinatal mortality rates (conventional calculation) for Blacks and Whites showed the expected crossover. However, analyses of post-LMP mortality showed no crossover. For the Black-White comparison, a hazard ratio of 1.72 (95% confidence interval: 1.67, 1.77) was obtained. The hazard was higher for smokers than for nonsmokers, but the hazard ratio increased from 1.09 (95% confidence interval: 0.98, 1.22) at 22 weeks to 1.82 (95% confidence interval: 1.72, 1.92) at 40 weeks. The hazard ratio associated with birth was also time dependent: higher than 1 for preterm gestation and lower than 1 for term gestation. The increasing adverse effect of smoking with gestational age suggests an accumulating effect of smoking on mortality. Modeling post-LMP mortality eliminates the crossover paradox for race and maternal smoking in a single statistical model.


Surgical treatment for pulmonary metastases in urogenital cancers.
The malignant disease's ability to metastasize remains one of the major obstacles when treating patients with cancer. The indication of metastasectomy is currently limited to patients undergoing treatment of the primary tumor. Resections for lung metastases of high selected patients with urogenital cancer present minimal risks and can prolong survival. Prognostic factors that determine which patients will benefit from surgery are still unclear. This article presents a retrospective analysis of patients who underwent lung metastases resection between 2008 and 2013 in our clinic. Among 148 patients, 8 (5.41%) had lung metastases after urologic cancers (UC), 18 (12.16%) after genital cancers (GC), 13 (8.78%) after breast tumors and 109 (73.65%) had lung metastases from other type of tumors. The overall 6 months survival was 100% for UC, 94.44 for GC, 84.62% for BC and 87.16% for others. The criteria for surgery proved to have a positive predictive value and what should be considered are the following: prolonged disease-free interval (DFI), unilateral disease, the absence of systemic pathologies, oncological margins resecability and less than 3 radioimagistic detectable metastases. A negative prognosis was observed in those with primary tumor in the cervix, at least 3 metastases and a tumor larger than 3 cm. To determine how to select surgical candidates for pulmonary metastasectomy more precisely, further analysis of prognostic factors is evident and the need for a prospective, randomized, multicenter study is clear.


Progress in the contemporary management of hemophilia: The new issue of patient aging.
The management of inherited coagulation disorders such as hemophilia A and B has witnessed dramatic progresses since the last few decades of the last century. Accordingly, persons with hemophilia (PWH) now enjoy a life expectancy at birth not different from that of males in the general population, at least in high income countries. Nowadays, a substantial proportion of PWH are aging, like their peers in the general population. This outstanding progress is accompanied by problems that are in part similar to those of any old person (multiple concomitant diseases and the resulting intake of multiple drugs other than those specific for hemophilia treatment). In addition, older PWH suffer from the consequences of the comorbidities that developed when their treatment was at the same time poorly available and unsafe. Typical hemophilia comorbidities affect the musculoskeletal system following joint and muscle bleeds, but also the liver and kidney are often impaired due to previous bloodborne infections such as viral hepatitis and HIV. Thus, the comorbidities of hemophilia superimposed on the multimorbidity and polypharmacy associated with aging create peculiar problems in the current management of these patients, that demand the coordinated holistic intervention of internists, geriatricians and clinical pharmacologists in addition to the care traditionally provided by pediatricians and hematologists.


Leptin receptor and neuropeptide Y gene expression in the sheep brain.
Leptin, a protein secretory product of adipocytes, is important in appetite control, energy balance and reproduction. In rodents, the physiological effects of leptin are centrally mediated, in part via the neuropeptide Y (NPY) system in the hypothalamus. The role of leptin in ruminants, where appropriate nutrition and reproductive status are of major economic concern, is largely unknown. To elucidate the function of leptin in sheep we have investigated putative sites of action for leptin in the brain and pituitary gland using both in-situ hybridization to detect expression of the signalling form of the leptin receptor (OB-Rb) and in-vitro autoradiography using (125I)leptin to detect sites of specific leptin binding. OB-Rb gene expression occurred in the hippocampus, cerebral cortex, preoptic area, stria terminalis and choroid plexus, and within the hypothalamus in the paraventricular (PVN), ventromedial (VHM) and arcuate (ARC) nuclei. OB-Rb gene expression in the ovine pituitary gland was not detected by in-situ hybridization. Sites of OB-Rb and NPY gene expression were compared using both in-situ hybridization on adjacent sections containing the arcuate and ventromedial nuclei, and dual in-situ hybridization on sections containing these areas. In serial sections, OB-Rb expression was found to correspond closely with that of NPY over the arcuate nuclei. Using dual in-situ hybridization, NPY expressing neurones in the arcuate nuclei were also positive for OB-Rb gene expression. Therefore, it appears that leptin may partly act via OB-Rb located on NPY neurones in the sheep hypothalamus as in the rodent.


[Echographic investigation of normal and pathological voiding (author's transl)].
A new urodynamic method is described which is based upon the principle of measuring the anteroposterior diameter of the urinary bladder during micturition by ultrasound. A 4 MHz transducer is placed vertically on the abdominal wall 6 to 7 cm above the symphysis and kept in a constant position by means of a special device. The continuously decreasing bladder diameter during micturition is recorded by M-mode echography (Echopan K, Siemens) and plotted as a diameter-time curve. Normals can be differentiated from patients with a subvesical outflow obstruction or a neurogenic disturbance of bladder emptying. For quantification the mean velocity of bladder diameter shortening during the first 30 seconds of micturition is calculated and correlated with the maximal uroflow (r = 0,77). Therefore a rough quantitative measurement of micturition seems to be possible.


Air Pollution and Temperature: a Systematic Review of Ubiquitous Environmental Exposures and Sudden Cardiac Death.
Environmental exposures have been associated with increased risk of cardiovascular mortality and acute coronary events, but their relationship with out-of-hospital cardiac arrest (OHCA) and sudden cardiac death (SCD) remains unclear. SCD is an important contributor to the global burden of cardiovascular disease worldwide. Current literature suggests a relationship between environmental exposures and cardiovascular disease, but their relationship with OHCA/SCD remains unclear. A literature search was conducted in PubMed, Embase, Web of Science, and Global Health. Of 5138 studies identified by our literature search, this review included 30 studies on air pollution, 42 studies on temperature, 6 studies on both air pollution and temperature, and 1 study on altitude exposure and OHCA/SCD. Particulate matter air pollution, ozone, and both hot and cold temperatures are associated with increased risk of OHCA/SCD. Pollution and other exposures related to climate change play an important role in OHCA/SCD incidence.


Exploration of thiaheterocyclic hHDAC6 inhibitors as potential antiplasmodial agents.
The recurring resistance of the malaria parasite to many drugs compels the design of innovative chemical entities in antimalarial research. Pan-histone deacetylase inhibitors (pan-HDACis) have recently been presented in the literature as powerful novel antimalarials, although their application is hampered due to toxic side effects. This drawback might be neutralized by the deployment of isoform-selective HDACis. In this study, 42 thiaheterocyclic benzohydroxamic acids, 17 of them being potent and selective hHDAC6 inhibitors, were tested to investigate a possible correlation between hHDAC6 inhibition and antiplasmodial activity. Four hHDAC6 inhibitors showed submicromolar potency against both a chloroquine-sensitive and a chloroquine-resistant strain of Plasmodium falciparum with high selectivity indices, pointing to the relevance of exploring hHDAC6 inhibitors as potential new antiplasmodial agents.


Kinetics and energetics of assembly, nucleation, and growth of aggregates and fibrils for an amyloidogenic protein. Insights into transition states from pressure, temperature, and co-solute studies.
The transition states for prenucleation assembly, nucleation, and growth of aggregates and amyloid fibrils were investigated for a dimeric immunoglobulin light chain variable domain, employing pressure, temperature, and solutes as variables. Pressure-induced aggregation was nucleation-dependent and first-order in protein concentration and could be seeded. The insoluble aggregates were mixtures of amyloid fibrils and amorphous aggregates. Activation volumes, activation surface areas, and activation waters of hydration were larger for aggregate growth than for prenucleation assembly or nucleation, although activation free energies were similar for the three processes. Activation free energies for each of the transition states were dominated by the unfavorable free energy of solvation of newly exposed surfaces. Equilibrium dissociation and unfolding of the dimer showed a much larger volume change than those required to form the transition states for the three processes. Thus, the transition states for these steps are similar to the native state, and their formation requires only small structural perturbations. Finally, the presence of Congo red during amyloid fibril formation shortened lag times and caused pressure insensitivity of nucleation, suggesting that this compound or its analogs may not be effective as inhibitors of amyloidosis.


Algibacter aquaticus sp. nov., a slightly alkaliphilic marine Flavobacterium isolated from coastal surface water.
A rod-shaped, pale yellow-pigmented, aerobic, Gram-staining-negative strain with gliding motility, designated as strain SK-16T, was isolated from the coastal surface water of a semi-enclosed coastal inlet in Misaki, Japan. Analysis of 16S rRNA gene sequences revealed that SK-16T represented a member of the family Flavobacteriaceae and was closely related to the genus Algibacter, with sequence similarities ranging from 95.9 to 94.3 % to the type strains of species of the genus Algibacter. The major cellular fatty acids were iso-C15 : 0, iso-C17 : 0 3-OH, iso-C15 : 0 G and iso-C15 : 0 3-OH. Major polar lipids were phosphatidylethanolamine, an aminophospholipid and an unidentified phospholipid. The DNA G+C content of SK-16T was 32.3 mol% and MK-6 was the only predominant isoprenoid quinone. On the basis of the results of phenotypic, genotypic, chemotaxonomic and phylogenetic studies, it was suggested that SK-16T represents a novel species within the genus Algibacter, with the newly proposed name Algibacteraquaticus. The type strain is SK-16T (=NBRC 110220T=KCTC 32974T).


Inflammatory markers C-reactive protein and PLR in relation to HCC characteristics.
Several markers of systemic inflammation, including blood C-reactive protein, platelet lymphocyte ratio (PLR) and neutrophil lymphocyte ratio (NLR) have been identified as independent prognosticators for hepatocellular carcinoma (HCC). To attempt to understand the significance of these markers, they were examined in relation to 4 tumour parameters, namely maximum tumour diameter (MTD), tumour multifocality, portal vein thrombosis (PVT) and blood alpha-fetoprotein (AFP) levels. Using linear and logistic regression models, we found that C-reactive protein and PLR on single variables, were statistically significantly related to the tumour parameters. In a logistic regression final model, CRP was significantly related to MTD, AFP and PVT, and the Glasgow Index significantly related to MTD and AFP. Results of the area under the receiver operating characteristic curves (ROC), showed that the areas for PLR and CRP were statistically significant for high versus low MTD and for presence versus absence of PVT. CRP alone was significant for high versus low AFP. These analyses suggest that the prognostic usefulness of the inflammatory markers PLR and CRP (but not NLR) may be due to their reflection of parameter values for tumour growth and invasiveness.


Radiofrequency catheter ablation of atrioventricular accessory pathways: experience in 179 patients.
Radiofrequency catheter ablation was used to treat 179 patients aged 5 to 79 (37 +/- 17) years. Six patients had multiple accessory pathways. The total number of accessory pathways was 188, 47 conducting only retrogradely; among them, 8 had retrograde decremental properties. The location of the accessory pathways was: 81 at the left lateral position; 13 left posterior; 15 left posteroseptal; 24 posteroseptal; 16 midseptal; 16 right posteroseptal; 17 anteroseptal and 6 right lateral. All patients were symptomatic and six had congenital heart disease. Initial success was achieved in 159 patients (88.8%). Ten out the 20 patients in whom ablation failed underwent a second attempt and success was obtained in all but 3 patients. Final success was accomplished in 166 patients (92.7%). There were 14 recurrences (7.8%) all successfully ablated during a second procedure. The mean procedure duration time was 80 +/- 60 minutes, the mean radiation exposure time was 31 +/- 26 minutes and the mean number of radiofrequency applications was 9 +/- 10. Three patients developed complete atrioventricular block during the procedure requiring permanent pacing, one patient had a perforation of a previously unknown congenital aneurysm of the aorta solved by surgery and one patient had a transient amaurosis after the procedure attributed to microembolization. Radiofrequency ablation of accessory pathways is a safe and effective treatment.


Predictive ability of a comprehensive incremental test in mountain bike marathon.
Traditional performance tests in mountain bike marathon (XCM) primarily quantify aerobic metabolism and may not describe the relevant capacities in XCM. We aimed to validate a comprehensive test protocol quantifying its intermittent demands. Forty-nine athletes (38.8±9.1 years; 38 male; 11 female) performed a laboratory performance test, including an incremental test, to determine individual anaerobic threshold (IAT), peak power output (PPO) and three maximal efforts (10 s all-out sprint, 1 min maximal effort and 5 min maximal effort). Within 2 weeks, the athletes participated in one of three XCM races (n=15, n=9 and n=25). Correlations between test variables and race times were calculated separately. In addition, multiple regression models of the predictive value of laboratory outcomes were calculated for race 3 and across all races (z-transformed data). All variables were correlated with race times 1, 2 and 3: 10 s all-out sprint (r=-0.72; r=-0.59; r=-0.61), 1 min maximal effort (r=-0.85; r=-0.84; r=-0.82), 5 min maximal effort (r=-0.57; r=-0.85; r=-0.76), PPO (r=-0.77; r=-0.73; r=-0.76) and IAT (r=-0.71; r=-0.67; r=-0.68). The best-fitting multiple regression models for race 3 (r2=0.868) and across all races (r2=0.757) comprised 1 min maximal effort, IAT and body weight. Aerobic and intermittent variables correlated least strongly with race times. Their use in a multiple regression model confirmed additional explanatory power to predict XCM performance. These findings underline the usefulness of the comprehensive incremental test to predict performance in that sport more precisely.


Characterization of the atrial natriuretic peptide system in the oviduct.
The atrial natriuretic peptide (ANP) gene is expressed in several extraatrial tissues in which ANP may be involved in the regulation of autocrine or paracrine functions. In the ovary, the synthesis of ANP, its binding sites, and a physiological role were found. The ANP system in the oviduct, however, is yet to be defined. The purpose of the present study was to determine whether the ANP system is present in the oviduct and then to define its function. The serial dilution curves of oviductal extracts in rat and rabbit were parallel to the standard curve of ANP. Molecular profiles using reverse phase HPLC indicated that the prohormone and processed circulating peptide were the main forms present. The immunoreactive ANP content of the oviduct was 27.07 +/- 4.41 pg/mg tissue wet wt (1.19 +/- 0.19 ng/oviduct; n = 10; at metestrus) in rats and 1.21 +/- 0.12 pg/mg tissue wet wt (0.15 +/- 0.01 ng/oviduct; n 12) in rabbits. In adult 4-day cycling rats, the immunoreactive ANP contents in oviducts had a cyclic change characterized by the lowest level at proestrus (14.59 +/- 3.24 pg/mg; n = 12). A distinct and strong ANP immunoreactivity was found in the mucosal layer of rat oviduct, and ANP messenger RNA was also detected in the oviduct by reverse transcriptase-PCR. Specific high affinity binding sites for iodinated rat ANP ([125I]rANP) were observed in the mucosal layer of the oviduct in rats and rabbits. Specific [125I]rANP bindings localized in the mucosal layer of rabbit oviduct showed an apparent dissociation constant (Kd) of 18.69 +/- 5.55 nM and a maximal binding capacity of 14.85 +/- 6.19 fmol/mm2. These specific [125I]rANP bindings were not reversed by des-[Gln18,Ser19,Gly20,Leu21,Gly22]ANP-(4- 23) as a selective ligand of clearance receptor. Synthetic ANP inhibited both the frequency and amplitude of basal motility of rabbit oviduct in a dose-dependent manner. These results suggest that the oviduct has its own ANP system, and the system is involved in the regulation of oviductal motility.


Crystallization and X-ray analysis of NH3-dependent NAD+ synthetase from Helicobacter pylori.
The ubiquitous NAD(+) synthetase catalyzes the key step in the biosynthesis of nicotinamide adenine dinucleotide. NH3-dependent NAD(+) synthetase from Helicobacter pylori was purified to homogeneity and crystallized using PEG 1500 as a precipitant. The crystal diffracted up to a resolution of 2.3+ and was found to belong to space group C2 with unit cell dimensions of a = 93.8, b = 48.3, c = 64.2 A and alpha = gamma = 90, beta = 110.0 degrees.


Characterization by restriction fragment length polymorphism and sequence analysis of field and vaccine strains of infectious laryngotracheitis virus involved in severe outbreaks.
At the end of 2002 and throughout 2003, there was a severe outbreak of infectious laryngotracheitis (ILT) in an intensive production area of commercial hens in the Sao Paulo State of Brazil. ILT virus was isolated from 28 flocks, and 21 isolates were genotyped by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) using four genes and eight restriction enzymes, and by partial sequencing of the infected cell protein 4 (ICP4) and thymidine kinase (TK) genes. Three groups resulted from the combinations of PCR-RFLP patterns: 19 field isolates formed Group I, and the remaining two isolates together with the chicken embryo origin (CEO) vaccine strains formed Group II. Group III comprised the tissue-culture origin (TCO) vaccine strain by itself. The PCR-RFLP results agreed with the sequencing results of two ICP4 gene fragments. The ICP4 gene sequence analysis showed that the 19 field isolates classified into Group I by RFLP-PCR were identical among themselves, but were different to the TCO and CEO vaccines. The two Group II isolates could not be distinguished from one of the CEO vaccines. The nucleotide and amino acid sequence analyses discriminated between the Brazilian and non-Brazilian isolates, as well as between the TCO and CEO vaccines. Sequence analysis of the TK gene enabled classification of the field isolates (Group I) as virulent and non-vaccine. This work shows that the severe ILT outbreak was caused by a highly virulent, non-vaccine strain.