Smac mimetics: implications for enhancement of targeted therapies in leukemia.
Drug resistance is a growing concern with clinical use of tyrosine kinase inhibitors. Utilizing in vitro models of intrinsic drug resistance and stromal-mediated chemoresistance, as well as functional mouse models of progressive and residual disease, we attempted to develop a potential therapeutic approach designed to suppress leukemia recurrence following treatment with selective kinase inhibitors. The novel IAP inhibitor, LCL161, [corrected] was observed to potentiate the effects of tyrosine kinase inhibition against leukemic disease both in the absence and presence of a stromal-protected [corrected] environment. LCL161 enhanced the proapoptotic effects of nilotinib and PKC412, against leukemic disease in vitro and potentiated the activity of both kinase inhibitors against leukemic disease in vivo. In addition, LCL161 synergized in vivo with nilotinib to reduce leukemia burden significantly below the baseline level suppression exhibited by a moderate-to-high dose of nilotinib. Finally, LCL161 displayed antiproliferative effects against cells characterized by intrinsic resistance to tyrosine kinase inhibitors as a result of expression of point mutations in the protein targets of drug inhibition. These results support the idea of using IAP inhibitors in conjunction with targeted tyrosine kinase inhibition to override drug resistance and suppress or eradicate residual disease.


Fiber-type composition of hindlimb muscles in the turtle, Pseudemys (Trachemys) scripta elegans.
A description is provided of the fiber-type composition of several hindlimb muscles of the adult turtle, Pseudemys (Trachemys) scripta elegans. In addition, cross-section areas of each fiber type and an estimation of the relative (weighted) cross-section area (wCSA) occupied by the different fiber types are also provided. Seven muscles were selected for study, based on their suitability for future neurophysiological analysis as components of the segmental motor system, and on their homologies with muscles in other vertebrates. The test muscles were iliofibularis (ILF), ambiens (AMB), external gastrocnemius (EG), extensor digitorum communis (EDC), flexor digitorum longus (FDL), tibialis anterior (TA), and peroneus anterior (PA). Serial sections of these muscles were stained for myosin adenosine triphosphatase (ATPase), NADH-diaphorase, and alpha-glycerophosphate dehydrogenase (alpha-GPDH), thereby enabling fiber-type classification on the basis of indirect markers for contraction speed and oxidative (aerobic) vs. glycolytic (anaerobic) metabolism. All muscles contained three fiber types: slow oxidative (SO; possibly including some non-twitch tonic fibers); fast oxidative glycolytic (FOG); and fast glycolytic (Fg). There were at least 30% FOG and 50% FOG + Fg fibers in the seven muscles, the extreme distributions being the predominantly glycolytic ILF vs. the predominantly oxidative FDL muscle (ILF--15.5% SO, 35.2% FOG, 49.3% Fg vs. FDL--49.1% SO, 41.1% FOG, 9.8% Fg). As in other species, the test muscles exhibited varying degrees of regional concentration (compartmentalization) of the different fiber types. This feature was most striking in ILF. Pronounced compartmentalization was also observed in AMB, EG, PA, TA, and EDC, whereas the distribution of fiber types in the highly oxidative FDL was homogeneous. In five of the seven muscles, fiber size was ranked with Fg > FOG > SO. In terms of wCSA, which provides a coarse-grain measure of the different fiber types' potential contribution to whole muscle peak force, all muscles exhibited a higher Fg and lower SO contribution to cross-section area than suggested by their corresponding fiber-type composition. The largest relative increase in wCSA vs. fiber-type composition were in the ILF and AMB muscles. We conclude that the turtle hindlimb provides some interesting possibilities for testing for a division of labor among different muscles during different movements (e.g., sustained vs. ballistic), and for study of the behavior of the different fiber (and motor unit) types under normal and perturbed conditions. The relationships between the present results and previous findings on homologous muscles of the mammalian (cat, rat) and reptilian (lizard) hindlimb are discussed.


Snail populations in arctic lakes: competition mediated by predation?
For 2 species of snails in arctic Alaskan lakes, I studied the patterns of snail distribution with respect to habitat, distribution of predatory fish, and the potential for interspecific competition. The snails Lymnaea elodes and Valvata lewisi co-exist in these arctic lakes, either in the presence of lake trout, Salvelinus namaycush, or in the absence of predation. Intensive sediment core sampling of Toolik Lake and Lake N-2, with trout and lacking trout, respectively, showed that the smaller snail, Valvata, was abundant in Toolik but ocurred at very low densities in Lake N-2. On the open sediments of lakes containing trout, diver surveys revealed very low densities of adult Lymnaea (0.12±0.12/m2), but similar surveys in lakes without trout revealed much higher densities of adult Lymnaea (7.1±1.8/m2). A survey of 14 lakes indicated that adult Lymnaea grew to a smaller mean size in lakes with trout than in lakes which lacked trout.In laboratory and field experiments, the presence of Lymnaea lowered the fecundity of Valvata. Laboratory experiments also showed that Lymnaea fecundity was enhanced by the presence of Valvata. Enhancement was not due to predation by Lymnaea on Valvata eggs or young. The observed patterns of distribution and abundance in the absence of trout, combined with results from laboratory experiments, are consistent with the hypothesis that competitive and facilitative interactions control the population dynamics of the two snails. The distribution and abundance patterns of snails where trout are present suggest that trout predation rather than competition controls snail population dynamics in lakes containing trout.


Systematic characterization of components of Makyo-kanseki-to granule and serum metabolomics for exploring its protective mechanism against acute lung injury in lipopolysaccharide-induced rats.
Makyo-kanseki-to has been used for the treatment of pneumonia, becoming a basic formula for coronavirus disease 2019. However, the chemical profile of Makyo-kanseki-to granule and its possible mechanism against acute lung injury from terminal metabolic regulation have been unclear. The aim of this study was to characterize the constituents in Makyo-kanseki-to granule and reveal the potential related mechanism of Makyo-kanseki-to granule treatment for acute lung injury using a rat model of lipopolysaccharide-induced acute lung injury. Totally, 78 constituents were characterized based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Makyo-kanseki-to granule could alleviate acute lung injury through modulating rectal temperature, pulmonary edema, histopathology, and processes of inflammatory and oxidative stress. Twenty-two potential biomarkers in acute lung injury rats were identified by metabolomics based on ultra-performance liquid chromatography coupled with quadrupole exactive high-field mass spectrometry. They were mainly involved in amino acids and glycerophospholipid metabolism, which were regulated by Makyo-kanseki-to granule. The present results not only increase the understanding of the chemical profile and molecular mechanism of Makyo-kanseki-to granule mediated protection against acute lung injury but also provide an experimental basis and new ideas for further development and clinical application of Makyo-kanseki-to granule.


A case of bilateral uveitis and optic disc swelling with Chiari I malformation.
We report a case of bilateral uveitis and optic disc swelling with Chiari I malformation. A 16-year-old girl was admitted to our clinic due to conjunctival hyperaemia and blurred vision in her right eye. Ophthalmologic and systemic examinations were performed. Visual acuity was 0.7 (OD) and 1.0 (OS). Bilateral optic disc swelling was observed. Fluorescein angiography demonstrated bilateral retinal vasculitis as well as optic disc hyperflourescence due to leakage. Laboratory examinations were within normal limits. Cranial magnetic resonance venography imaging revealed neither cranial mass nor cerebral venous thrombosis but a Chiari I malformation. The patient was started oral cetazolamid, topical and oral corticosteroids. After six months follow-up, bilateral optic disc swelling was resolved completely and visual acuity was 1.0 in both eyes. Optic disc swelling may be associated with intraocular inflammation; however, patients with bilateral optic disc swelling should be suspected of having an accompanying intracranial pathology.


Latency and loss of pulse oximetry signal with the use of digital probes during prehospital rapid-sequence intubation.
Prehospital personnel rely on timely and accurate pulse oximetry data when performing critical skills, such as rapid-sequence intubation (RSI). However, loss of signal may be a frequent occurrence in patients with poor peripheral perfusion. In addition, a delay or latency period in the timeliness of pulse oximetry data may exist with probes placed on the fingers. To define the incidence of pulse oximetry signal loss or a latent period during prehospital RSI. Patients with severe traumatic brain injury (TBI) (Glasgow Coma Scale score [GCS] 3-8) undergoing prehospital RSI by air medical crews were enrolled. Data from hand-held oximetry-capnometry units were analyzed for either the loss of a pulse oximetry tracing (≥ 30 seconds) during the RSI procedure or the presence of a latent period, defined by the saturation of peripheral oxygen (SpO(2)) nadir occurring after intubation in patients undergoing desaturation (SpO(2) ≤ 93%) during the procedure. A total of 98 of 124 patients (79%, 95% confidence interval [CI] 71-85%) had pulse oximetry failure during critical points in the RSI procedure. In the 49 patients with a desaturation during RSI, a latent period was observed in 27 patients (55%, 95% CI 41-68%). A high incidence of pulse oximetry failure was observed with the use of a digital pulse oximetry probe during prehospital RSI. In addition, a latent period appears to exist in the majority of patients undergoing desaturation.


Electro-clinical and imaging characteristics of focal cortical dysplasia: correlation with pathological subtypes.
Focal cortical dysplasia (CD) is a common cause of pharmaco-resistant epilepsy. CD is due to abnormalities in neuronal migration, proliferation, and/or differentiation that result in four distinct pathological subtypes: 1A, 1B, 2A, and 2B. In order to provide clinical correlation to these pathological subtypes, we reviewed the electro-clinical and imaging characteristics and surgical outcomes of the four pathological subtypes of CD. We retrospectively reviewed patient data from epilepsy surgeries at the Cleveland Clinic Foundation between 1990 and 2002. Only those patients with the definite pathological diagnosis of isolated cortical dysplasia were included in the study (n = 145). Pathological subtypes 2A and 2B were predominantly frontal in location, and had a more severe epilepsy syndrome with lower intelligence quotient scores than subtypes 1A and 1B. Patients with subtype 1A FCD had less severe, later onset epilepsy that was predominantly located in the temporal lobe. Risk factors for epilepsy included febrile seizures for type 1A, head trauma for types 1A and 1B, and perinatal adverse events for type 2B. Type 2B demonstrated significantly more FLAIR signal abnormalities than the other groups. Sixty-three percent of patients overall had an Engel I outcome at 6 months follow-up. The best outcomes were in the 2B subtype, and in those who did not require an invasive EEG evaluation. Clinically important differences exist between the pathological subtypes of CD, which may assist in their management, and provide further insight into their underlying pathophysiology.


Effects of variation in Eucalyptus essential oil yield on insect growth and grazing damage.
Levels of insect attack and yields of leaf essential oils in Eucalyptus vary widely within and among species. We tested the hypotheses that 1) metabolic cost of oil detoxification increases with increasing oil yield, resulting in lower herbivore growth rates and, consequently, 2) in lower herbivore damage to plants. Distribution of insect damage, eggs, immature insects and adults and feeding rates, growth and survivorship of insects do not support the hypotheses, although a threshold level of oil may be necessary to influence herbivorous insects. Herbivorous beetles tested do not detoxify essential oils. Levels of leaf nitrogen, rather than oil content, explained differences in insect feeding and growth.


Regulating the ribosome: a spotlight on RNA dark matter.
In this issue, Pircher et al. (2014) show that an abundant ribosome-associated 18 nt noncoding RNA (ncRNA), derived from the open reading frame of an mRNA, acts directly on the ribosome and regulates global translation levels in response to hypertonic shock.


Effects of endotoxic shock on right ventricular systolic function and mechanical efficiency.
To investigate the effects of endotoxin infusion on right ventricular (RV) systolic function and mechanical efficiency. Six anesthetized pigs (Endo group) received a 0.5 mg/kg endotoxin infusion over 30 min and were compared with six other anesthetized pigs (Control group) receiving placebo for 5 h. RV pressure-volume (PV) loops were obtained by the conductance catheter technique and pulmonary artery flow and pressure were measured with high-fidelity transducers. RV adaptation to increased afterload during the early phase of endotoxin-induced pulmonary hypertension (T30) was obtained by both homeometric and hetereometric regulations: the slope of the end-systolic PV relationship of the right ventricle increased from 1.4+/-0.2 mmHg/ml to 2.9+/-0.4 mmHg/ml (P<0.05) and RV end-diastolic volume increased from 56+/-6 ml to 64+/-11 ml (P<0.05). Consequently, right ventricular-vascular coupling was maintained at a maximum efficiency. Ninety minutes later (T120), facing the same increased afterload, the right ventricle failed to maintain its contractility to such an elevated level and, as a consequence, right ventricular-vascular uncoupling occurred. PV loop area, which is known to be highly correlated with oxygen myocardial consumption, increased from 1154+/-127 mmHg/ml (T0) to 1798+/-122 mmHg/ml (T180) (P<0.05) while RV mechanical efficiency decreased from 63+/-2% (T0) to 45+/-5% (T270) (P<0.05). In the very early phase of endotoxinic shock, right ventricular-vascular coupling is preserved by an increase in RV contractility. Later, myocardial oxygen consumption and energetic cost of RV contractility are increased, as evidenced by the decrease in RV efficiency, and right ventricular-vascular uncoupling occurs. Therefore, therapies aiming at restoring right ventricular-vascular coupling in endotoxic shock should attempt to increase RV contractility and to decrease RV afterload but also to preserve RV mechanical efficiency.


High-resolution melting of multiple barcode amplicons for plant species authentication.
In recent years, species identification in herbs has attracted considerable attention due to several cases of fraud; hence inexpensive high-throughput authentication methods are highly welcomed. Species authentication is often performed through DNA analysis and several specific regions (barcodes) are considered suitable. Each barcode (Bar) possesses different qualities in terms of universality and discrimination power. A multiplexed format where information can be extracted simultaneously from several barcode regions is seemingly appropriate to ensure the power of both universality and discrimination. In this approach, we amplified DNA from five different barcode regions in a multiplexed PCR format followed by high-resolution melting (HRM). This multiplexed Bar-HRM approach was first applied to plants spanning the plant kingdom and then gradually narrowing down the genetic variability within the Lamiaceae and the Solanaceae families to finally reach closely related cultivars. Universality was demonstrated through distinct melting profiles obtained for species originating from 29 different families spanning the angiosperms, gymnosperm, mosses, and liverwort (Marchantiophyta). Discrimination power was retained for species, sub-species, and a few cultivars through the application of multivariate statistics to the high-resolution melting profiles. This preliminary investigation has shown the potential to discriminate a vast amount of species within the whole plant kingdom. It requires no a priori knowledge of the species' DNA sequence and occurs in a closed system within 2.5 h at a reduced cost per sample compared to other DNA based approaches.


A Review on Classification and Biological Activities of Alkaloids from the Genus Zanthoxylum Species.
Many plants in the genus Zanthoxylum, belonging to the Rutaceae family, are used as folk medicines for the treatment of various diseases, which have gained much attention for their phytochemical and pharmacological activity investigations. Alkaloids are the largest secondary metabolites with structurally diverse types found in this genus and they demonstrate a wide range of biological activities. The aim of this review is to provide a summary on the isolation, classification, and biological properties of alkaloids from Zanthoxylum species, which also will bring more attention to other researchers for further biological study on alkaloids for the new drug development.


c-Kit receptor (CD117) expression on myeloblasts and white blood cell counts in acute myeloid leukemia.
The c-Kit receptor is considered to play a crucial role in hematopoiesis. Induction of mobilization of hematopoietic cells in the bone marrow requires cooperative signaling through c-Kit and c-Kit ligand pathway, and these interactions are important in the retention of stem cells within the bone marrow. Therefore, we analyzed c-Kit density on the leukemic myeloblasts of patients with acute myeloid leukemia (AML) in relation to white blood cell count (WBC) in the peripheral blood. Bone marrow aspirates collected from patients with AML and bone marrow aspirates and leukapheresis products after granulocyte colony-stimulating factor blood mobilization from adult volunteers were studied. To determine the level of c-Kit receptor expression, we applied quantitative (relative fluorescence intensity and antibody binding per cell) cytometric methods. Our data showed negative correlation between the level of c-Kit expression intensity on myeloblasts and the number of leukocytes in blood of AML patients. The c-Kit receptor density on myeloblasts in patients with low WBC was significantly stronger than that on myeloblasts in patients with high WBC. In the latter patient group, the density c-Kit receptor on myeloblasts was similar to that on CD34(+) cells in mobilized peripheral blood. The obtained data suggest an involvement of c-Kit receptor in the regulation of leukemic myeloblasts egress to the peripheral blood.


A semi-synthetic flavonoid from Bauhinia pulchella stem attenuates inflammatory osteolysis in periodontitis in rats: Impact on cytokine levels, oxidative stress, and RANK/RANKL/OPG pathway.
Many species of theBauhinia genus have been widely used in folk medicine as analgesic, anti-inflammatory and antioxidant agents. (-)-Fisetinidol palmitate is a semi-syntetic flavonoid obtained from the ethanolic extract of the stem of Bauhinia pulchella. This study aimed to evaluate the antiresorptive effect of the semi-syntetic (-)-fisetinidol palmitate in ligature-induced periodontitis in rats. Also, it evaluated the mechanism of action of (-)-fisetinidol palmitate and its toxicity. Periodontitis was inducedvia a nylon thread ligature (3.0) around the second upper left molars. Rats were treated (oral gavage) once a day for 11 days with (-)-fisetinidol palmitate (0.01 or 0.1 mg/kg) or saline vehicle. (-)-Fisetinidol palmitate (0.1 mg/kg) reduced alveolar bone loss, increased bone alkaline phosphatase (BALP), superoxide dismutase (SOD), and catalase (CAT) activity; also, it decreased IL1-β, IL-8/CINC-1, nitrite/nitrate levels and myeloperoxidase activity. (-)-Fisetinidol palmitate reduced the mRNA levels of IL1-β, IL-6, RANK, and RANK-L, while it increased the OPG ones. No statistical differences (P > 0.05) were observed in the transaminases (ALT, AST) and Total Alkaline Phosphatase (TALP) levels among groups. Fisetinidol palmitate did not result in any signs of toxicity and had anti-resorptive effects in a pre-clinical trial of periodontitis, showing antioxidant activity with the involvement of the RANK/RANKL/OPG pathway.


Encapsulated probiotic cells: Relevant techniques, natural sources as encapsulating materials and food applications - A narrative review.
The administration of probiotic microorganisms in adequate amounts is constantly related to health benefits. To promote beneficial effects, these microorganisms must not be affected by exposure to environmental factors and must be able to adhere and colonize the human gastrointestinal tract. Several encapsulation techniques and encapsulating materials are available to produce probiotic particles, however, it is essential that the process must not be aggressive, reducing or preventing injuries and cell losses, besides, the particle properties obtained must be adequate for the proposed purpose. At the same time, the global market for supplements and probiotic foods has been growing significantly, and cell encapsulation appears as an alternative to incorporate probiotics into different food matrices. This review discusses and updates the main techniques, and the traditional and emerging polysaccharides for encapsulation of probiotic cells, as well as the advantages and possibilities of incorporating produced particles into food matrices. Currently, various scientific studies report the use of different encapsulation techniques, such as extrusion, emulsion, spray drying, spray chilling and fluidized bed to encapsulate probiotics properly. The alginate is still widely used to produce probiotic particles, however, there has been a growing interest in its total or partial substitution with others polysaccharides, such as gums, mucilages, prebiotic compounds and microbial exopolysaccharides, which improve the protection and survival of encapsulated cells and allow their incorporation into dairy and non-dairy food products.


[Population genetic analysis of the association between the BRCA1 and P53 gene polymorphisms and the risk of sporadic breast cancer].
Polymorphism of two tumor-suppressor genes, BRCA1 and P53, was examined. DNA was extracted from blood leukocytes of the women affected with breast cancer (N = 151) and of the women with no clinical symptoms of tumor diseases (N = 191). Typing of the polymorphic variants was performed using PCR-RFLP method. It was demonstrated that the genetic structure of the patient group (taking into consideration BRCA1 and P53 polymorphic variants) differed from that of the control group. The group of genotypes, found exclusively among the patients, as well as the group of "resistant" genotypes revealed predominantly among the controls, was described. Detection of the genotype A1A1 B1B1 S1S1 C1C1 F1F1 J2J2, whose frequency in control group was eight times higher than in the patient group, was an additional confirmation of the existence of "resistant" genotypes. These findings point to the association between the combinations of the BRCA1 and P53 allelic variants and the risk of breast cancer.


In situ generation of bioadhesives using dry tannic silk particles: a wet-adhesion strategy relying on removal of hydraulic layer over wet tissues for wound care.
Tissue adhesives have been widely used in biomedical applications. However, the presence of a hydrated layer on the surface of wet tissue severely hinders their adhesion capacities, resulting in ineffective wound treatment. To address this issue, a dry particle dressing (plas@SF/tann-hydro-pwd) capable of removing the hydrated layer and converting in situ to bioadhesives (plas@SF/tann-hydro-gel) was fabricated via simple physical mixing based on the hydrophobic-hydrogen bonding synergistic effect and Schiff-base reaction. It was found that the plas@SF/tann-hydro-gel bioadhesive, which was changed from plas@SF/tann-hydro-pwd dressing by adsorption of water, exhibited good wet adhesion to diverse biological tissues. In addition, the wet adhesion qualities of the plas@SF/tann-hydro-gel adhesive was studied under a variety of demanding conditions, including a wide range of temperatures, varying pH levels, highly concentrated salt solutions, and simulated fluids. Experiments on animals had showed that the adhesive plas@SF/tann-hydro-gel has superior wet adhesion qualities and superior wound healing properties compared to the commercial product Tegaderm™. This study develops a new wet-adhesion technique employing dry particle dressing to eliminate the hydrated layer over wet tissues for the in situ creation of gel bioadhesives for wound healing.


Increased susceptibility of SARS-CoV2 infection on oral cancer patients; cause and effects: An hypothesis.
In 2019, a new coronavirus (SARS CoV2) infecting humans has emerged in Wuhan, China which caused an unprecedented pandemic involving at least 185 countries infecting 2.5 million people till date. This virus is transmitted directly or indirectly through the upper aerodigestive tract. As it is evident from the recent studies that SARS-CoV-2 requires host enzyme Furin to activate receptor binding domain of its S protein and host Angiotensin Convertase Enzyme 2 (ACE2) is required as binding receptor, facilitating the entry of virus into the host cell. Evidence from literature shows that oral cancer tissues as well as paracarcinoma tissue exhibit higher expression of both Furin and ACE2, giving rise to the hypothesis that patients with oral cancer have higher chances of SARS CoV2 infection. It is also hypothesised that there will be increased severity of disease due to facilitated entry of the virus into the cells. Therefore, we suggest oral cancer patients require extra attention during COVID-19 pandemic and re-evaluation of current treatment paradigms in oral oncology is also needed.


Autologous human macrophages and anti-tumour cell therapy.
Most technical problems concerning the production of human macrophages have been resolved by cultures in hydrophobic plastic, gas-permeable bags. This process enables collection of non-adherent macrophages and is well adapted to the safety requirements of cell therapy. Under optimized culture conditions, about one billion macrophages are currently obtained from a single leukapheresis product. In most clinical trials, macrophages have been activated by interferon-gamma (IFNgamma). The injections have little or no toxic effect. The anti-tumour activity of the intravenous (i.v.) administrations is more pronounced in certain protocols than in others. The mechanism remains poorly understood. In vitro, the cytolytic effect of macrophages requires cell-to-cell contact but macrophages injected i.v. show no particular tropism for tumour tissue. This could result from modifications in adhesion molecules occurring during monocyte-macrophage differentiation which might modify recruitment in inflammatory foci. Macrophages can, however, infiltrate tumour cell clusters, which could explain their improved efficacy when injected intratumorally (i.t.). Moreover, several arguments would favour the use of macrophages as human tumour antigen-presenting cells (APCs). In vitro, macrophages are as efficient as monocyte-derived dendritic cells (MDDCs) in stimulating cytotoxic T lymphocyte (CTL) clones or circulating CTL precursors.


Comparison of respiratory virus detection rates for infants and toddlers by use of flocked swabs, saline aspirates, and saline aspirates mixed in universal transport medium for room temperature storage and shipping.
A nylon flocked swab/universal transport medium collection method developed for bacterial sexually transmitted infections was adapted to detect respiratory viruses in infants and toddlers. This method significantly outperformed the traditional use of nasal aspirates in terms of PCR-based virus detection (P = 0.016), and the samples were easier for clinicians to evaluate, store, and transport.


Vacancy-induced tensile strain of CdS/Bi2S3 as a highly performance and robust photocatalyst for hydrogen evolution.
Lattice strain is a new strategy for promoting photocatalytic activity in order to source more sustainable energy. Vacancy-induced strain is an effective tactic for lattice deformation. Herein, a CdS/Bi2S3 heterojunction structure containing sulfur vacancies (CdS/Bi2S3-VS) is synthesized by a one-step solvothermal method. When there are sulfur vacancies in the Bi2S3 lattice (Bi2S3-VS), the surrounding atoms move toward sulfur vacancies. This phenomenon lengthens the bonds between surrounding atoms, resulting in tensile stress. Strain engineering adjusts the energy band structure to reduce the interface barrier height, thus effectively improving the interface charge transfer rate. Moreover, density functional theory (DFT) calculations explore the influence of different strain levels on the band structure and Gibbs free energy. The strain-regulated band structure provides a new approach and effectively reduce the interface barrier.


Prophylaxis of lipopolysaccharide-induced shock by alpha-galactosylceramide.
The NKT cell ligand alpha-galactosylceramide and its synthetic homologue KRN7000 stimulate rapid and copious secretion of IFN-gamma and TNF-alpha release, both of which are key mediators of LPS-induced shock. We showed that KRN7000, injected before or within 2 h after LPS challenge, was able to prevent endotoxic shock. KRN7000 induced survival when the mice were injected 6, 9, or 12 days before the first injection of LPS, and this protective effect was associated with reduction upon subsequent challenge in the levels of IFN-gamma, TNF-alpha, MCP-1, and an increase of IL-10. Further analysis showed that the animals treated with KRN7000 prior to LPS challenge had lower numbers of F4/80+, NKT, and NK cells and lower percentages of NKT cells that stained for intracytoplasmic IFN-gamma when compared with mice that were not treated with KRN7000. When MCP-1 was injected in KRN7000-treated mice, the lethal effect of LPS challenge was restored, and the numbers of F4/80+, NKT, and NK cells increased to levels similar to those in untreated mice following LPS challenge. Taken together, our data demonstrated that KRN7000, injected from 6 to 12 days before the first administration of LPS, prevented endotoxin shock by inhibiting IFN-gamma, TNF-alpha, and MCP-1 release.


STARD5 specific ligand binding: comparison with STARD1 and STARD4 subfamilies.
We present herein a review of our recent results on the characterization of the binding sites of STARD1, STARD5 and STARD6 using NMR and other biophysical techniques. Whereas STARD1 and STARD6 bind cholesterol, no cholesterol binding could be detected for STARD5. However, titration of STARD5 with cholic acid and chenodeoxycholic acid led to specific binding. Using perturbation of the (1)H-(15)N-HSQC spectra and the sequence specific NMR assignments, we identified the amino acids in contact with those ligands. The most perturbed residues in presence of ligands are lining the internal cavity of the protein. Interestingly, these residues are not conserved in STARD1 and STARD6 and could therefore be key structural determinants of the specificity of START domains toward their ligands. We highlight three tissues expressing STARD5 that are affected by bile acids.


Neuropathology of viral infections of the central nervous system.
Many viral infections of the nervous system cause stereotyped pathologic features and overlapping clinical and imaging features. Neuroimaging usually offers neuroanatomical localization of the pathology, degree of involvement of the nervous system, and response to therapy during follow up in a few instances. Neuroimaging is a useful adjunct for diagnosis.


Experimental sulfate amendment alters peatland bacterial community structure.
As part of a long-term, peatland-scale sulfate addition experiment, the impact of varying sulfate deposition on bacterial community responses was assessed using 16S tag encoded pyrosequencing. In three separate areas of the peatland, sulfate manipulations included an eight year quadrupling of atmospheric sulfate deposition (experimental), a 3-year recovery to background deposition following 5years of elevated deposition (recovery), and a control area. Peat concentrations of methylmercury (MeHg), a bioaccumulative neurotoxin, were measured, the production of which is attributable to a growing list of microorganisms, including many sulfate-reducing Deltaproteobacteria. The total bacterial and Deltaproteobacterial community structures in the experimental treatment differed significantly from those in the control and recovery treatments that were either indistinguishable or very similar to one another. Notably, the relatively rapid return (within three years) of bacterial community structure in the recovery treatment to a state similar to the control, demonstrates significant resilience of the peatland bacterial community to changes in atmospheric sulfate deposition. Changes in MeHg accumulation between sulfate treatments correlated with changes in the Deltaproteobacterial community, suggesting that sulfate may affect MeHg production through changes in the community structure of this group.


Impact of ovarian hormones on the modulation of the serotonin transporter by fluvoxamine.
Most preclinical studies examining the mechanism(s) of action of antidepressants are carried out using male animals. Blockade of serotonin transporter (SERT) function by selective serotonin reuptake inhibitors (SSRIs) is the initial event that triggers a not completely understood process that results in clinical improvement in depression. To investigate whether there are differences in the ability of SSRIs to inhibit the SERT between male and female rats at different phases of the estrous cycle, clearance of locally applied serotonin (5-HT) was measured by in vivo chronoamperometry. Local application of the SSRI, fluvoxamine, directly into the CA3 area of hippocampus increased significantly 5-HT clearance time parameters in male rats and female rats in estrus or diestrus, but not in proestrus. The contribution of ovarian steroids to this result was investigated in ovariectomized (OVX) rats treated with estradiol benzoate (EB) and/or progesterone (P). In OVX-control rats, fluvoxamine increased clearance time parameters, whereas EB and/or P treatment blocked this effect, consistent with what was seen in female rats in proestrus. This effect was gender-specific, since treatment of castrated rats with EB/P had no effect on the ability of fluvoxamine to slow 5-HT clearance. The time course of hormonal effects showed that 1-60 min after local application of 17-beta-estradiol (E(2)) into the CA3 region of OVX rats, fluvoxamine had no effect on clearance time of 5-HT. E(2)-BSA mimicked E(2)'s effects at 10 min but not at 60 min. Pretreatment with estrogen receptor antagonists blocked the effects of E(2). The finding that acutely both estradiol and progesterone can inhibit the ability of an SSRI to slow the clearance of 5-HT, may have important implications for the use of SSRIs in women.


The effect of felodipine on ventricular fibrillation after coronary artery ligation in the anaesthetized pig.
A 10 min ligation of the left anterior descending coronary artery in anaesthetized pigs resulted in ventricular fibrillation (VF) in 70% of control and propranolol-treated animals. Felodipine (10 nmol kg-1) not only reduced ventricular ectopic activity by 90%, but also completely abolished VF. When a second occlusion was applied after 20 min of reperfusion, felodipine was less effective against VF, possibly due to decreasing felodipine concentrations or only a transient increase in VF threshold.


Opposing effects of curcuminoids on serum stimulated and unstimulated angiogenic response.
Curcumin is known to be a potent wound healer. Despite this, studies on curcumin using certain model systems have shown it to be anti-angiogenic. Results of the present investigations suggest that curcumin causes opposing effects on angiogenesis in serum stimulated and unstimulated conditions. The evidence in support of this are: (a) in serum free conditions, curcumin promoted sprouting in rat aortic ring, increased vascular density in CAM and induced morphological changes indicative of angiogenic phenotype in HUVECs and rat aortic endothelial cells in culture, (b) increased the expression of biochemical markers of angiogenesis such as CD 31, E-selectin, VEGF and VEGFR-2 in HUVECs on treatment with curcumin, and (c) supplementation of curcumin along with serum caused decrease in CD 31 and E-selectin levels, downregulation of VEGF, angiopoietin-1 and VEGFR-2 and delayed formation of capillary network-like structure. Proangiogenic effect of the individual components of the natural curcumin differed and the presence of the three components in the natural mixture has a synergistic effect. Effect of curcuminoids in the absence of serum appears to depend on VEGF as (a) anti-VEGF antibody blocked the effect of curcuminoids (b) curcuminoids caused decrease in PAR modification of VEGF increasing its biological activity. Treatment with curcuminoids in serum-free conditions resulted in activation of PI3K-Akt pathway; but in serum-supplemented condition, curcuminoids caused inhibition of the MAPK pathways thereby inhibiting the expression of angiogenic phenotype. These results suggest that PI3K-Akt and MAPK pathways involved in the expression of angiogenic phenotype respond differently to the extracellular microenvironment.


Evaluation of clinical competence and its related factors among ICU nurses in Kermanshah-Iran: A cross-sectional study.
The present study was conducted to evaluate the clinical competence and its related demographic factors among critical care nurses in Kermanshah, Iran. In this cross-sectional study, 155 Iranian nurses were selected by stratified random sampling. The data collection tools included a personal information form and the "Nurse Competence Scale". Data were analyzed using descriptive and analytical statistics. The mean score of nurses' clinical competence was equal to 76.14 ± 1.59 out of 100, which was at a "very good level". The mean score of using clinical competence in practice was equal to 70.38 ± 15.25 out of 100, which was at a "good level". Among the subscales of clinical competence, the highest mean score was related to "managing situation". The mean score of "using clinical competence in practice" was related to the subscale of "therapeutic interventions". There was no statistically significant difference among the score of clinical competence of nurses varying with different gender, age, academic degree, and work experience. The clinical competence of critical care nurses in Kermanshah was at a "very good" level, and the use of clinical competence in practice was at a "good level." Given the importance of clinical competencies in practice, nurses' clinical competence should be evaluated objectively and positive measures should be taken to promote the application of their clinical competence.


A palynological record of mangrove biogeography, coastal geomorphological change, and prehistoric human activities from Cedar Keys, Florida, U.S.A.
Under the continuous warming trend in the 21st century, mangroves are likely to migrate into more temperate regions in North and South America. However, the biogeography of different mangrove species is still unclear, especially near their latitudinal range limits in the two continents. This study utilizes palynological, geochemical, and sedimentological analyses to record changes in the coastal morphology and vegetation during the Holocene in Cedar Keys, Florida, the mangrove sub-range limit in North America. The multi-proxy dataset indicates that the milder winters during the Medieval Climate Anomaly likely facilitated the establishment of mangroves in the study region, where Avicennia, Laguncularia, and Rhizophora were established in the ~12th (790-850 cal yr BP), ~14th (580-660 cal yr BP), and ~ 16th century (440-460 cal yr BP), respectively. Thus, the Medieval Climate Anomaly likely triggered the poleward mangrove migration in North and South America synchronously. Moreover, the multi-proxy dataset also documents the obliteration of the Woodland Culture near Cedar Keys, where a once-thriving native civilization on Seahorse Key was driven out by the European colonizers, who settled on the mainland and Atsena Otie Key. Over time, the relict sites of the Woodland people on Seahorse Key were covered by mangroves and marsh vegetation since the ~16th century. Overall, our dataset suggests that industrial-era warming may have intensified the poleward mangrove expansion, although this trend had started earlier during the Medieval Climate Anomaly.


Biosorption of heavy metals by microorganisms: Evaluation of different underlying mechanisms.
Globally, ecotoxicologists, environmental biologists, biochemists, pathologists, and other experts are concerned about environmental contamination. Numerous pollutants, such as harmful heavy metals and emerging hazardous chemicals, are pervasive sources of water pollution. Water pollution and sustainable development have several eradication strategies proposed and used. Biosorption is a low-cost, easy-to-use, profitable, and efficient method of removing pollutants from water resources. Microorganisms are effective biosorbents, and their biosorption efficacy varies based on several aspects, such as ambient factors, sorbing materials, and metals to be removed. Microbial culture survival is also important. Biofilm agglomerates play an important function in metal uptake by extracellular polymeric molecules from water resources. This study investigates the occurrence of heavy metals, their removal by biosorption techniques, and the influence of variables such as those indicated above on biosorption performance. Ion exchange, complexation, precipitation, and physical adsorption are all components of biosorption. Between 20 and 35 °C is the optimal temperature range for biosorption efficiency from water resources. Utilizing living microorganisms that interact with the active functional groups found in the water contaminants might increase biosorption efficiency. This article discusses the negative impacts of microorganisms on living things and provides an outline of how they affect the elimination of heavy metals.


Effective passivation of Ag nanowire network by transparent tetrahedral amorphous carbon film for flexible and transparent thin film heaters.
We developed effective passivation method of flexible Ag nanowire (NW) network electrodes using transparent tetrahedral amorphous carbon (ta-C) film prepared by filtered cathode vacuum arc (FCVA) coating. Even at room temperature process of FCVA, the ta-C passivation layer effectively protect Ag NW network electrode and improved the ambient stability of Ag NW network without change of sheet resistance of Ag NW network. In addition, ta-C coated Ag NW electrode showed identical critical inner and outer bending radius to bare Ag NW due to the thin thickness of ta-C passivation layer. The time-temperature profiles demonstrate that the performance of the transparent and flexible thin film heater (TFH) with the ta-C/Ag NW network is better than that of a TFH with Ag NW electrodes due to thermal stability of FCVA grown ta-C layer. In addition, the transparent and flexible TFHs with ta-C/Ag NW showed robustness against external force due to its high hardness and wear resistance. This indicates that the FCVA coated ta-C is promising passivation and protective layer for chemically weak Ag NW network electrodes against sulfur in ambient.


Selective listening modifies activity of the human auditory cortex.
We have studied the effect of selective listening on the neuromagnetic evoked activity of the human auditory cortex. In the word categorization experiment the stimuli were 5-letter words, each beginning with (k). Half of them were targets, i.e., names of animals or plants, and half other meaningful Finnish words. In the duration discrimination experiment equiprobable tones of 425 ms (targets) or 600 ms duration were presented. In both experiments the interstimulus interval (ISI) was 2.3 s and the stimuli of the two classes were presented randomly. Subjects either ignored the stimuli (reading condition) or counted the number of targets (listening condition). The magnetic field over the head was measured with a 7-channel 1st-order SQUID-gradiometer. The stimuli evoked a transient response followed by a sustained field. The transient response did not differ between the two conditions but the sustained field was significantly larger in the listening than reading condition; the increase began 120-200 ms after stimulus onset and continued for several hundred milliseconds. The equivalent source locations of both transient and sustained responses agreed with activation of the supratemporal auditory cortex. In the dichotic listening experiment 25-ms square-wave stimuli were presented randomly and equiprobably either to the left or to the right ear at an ISI of 0.8-1 s, either alone or in presence of a speech masker. Counting the stimuli of either ear resulted in differences between responses to relevant and irrelevant sounds. The difference began 140-150 ms after stimulus onset and peaked at 200-240 ms. During monaural speech masking, N100m was larger for attended than ignored stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)


Automatic recognition of myeloma cells in microscopic images using bottleneck algorithm, modified watershed and SVM classifier.
Plasma cells are developed from B lymphocytes, a type of white blood cells that is generated in the bone marrow. The plasma cells produce antibodies to fight with bacteria and viruses and stop infection and disease. Multiple myeloma is a cancer of plasma cells that collections of abnormal plasma cells (myeloma cells) accumulate in the bone marrow. The definitive diagnosis of multiple myeloma is done by searching for myeloma cells in the bone marrow slides through a microscope. Diagnosis of myeloma cells from bone marrow smears is a subjective and time-consuming task for pathologists. Also, because of depending on final decision on human eye and opinion, error risk in decision may occur. Sometimes, existence of infection in body causes plasma cell's increment which could be diagnosed wrongly as multiple myeloma. The computer diagnostic process will reduce the diagnostic time and also can be worked as a second opinion for pathologists. This study presents a computer-aided diagnostic method for myeloma cells diagnosis from bone marrow smears. At first, white blood cells consist of plasma cells and other marrow cells are separated from the red blood cells and background. Then, plasma cells are detected from other marrow cells by feature extraction and series of decision rules. Finally, normal plasma cells and myeloma cells could be classified easily by a classifier. This algorithm is applied on 50 digital images that are provided from bone marrow aspiration smears. These images contain 678 cells: 132 normal plasma cells, 256 myeloma cells and 290 other types of marrow cells. Applying the computer-aided diagnostic method for identifying myeloma cells on provided database showed a sensitivity of 96.52%; specificity of 93.04% and precision of 95.28%.


Successful surgical treatment for a single coronary artery arising from the pulmonary artery.
The case of a 17-day-old infant who underwent correction of an aortic coarctation with pulmonary artery banding for ventricular septal defect is reported. Ischemic cardiac failure 3 weeks later led the authors to diagnose a single coronary artery originating from the pulmonary artery. At the age of 2 months, the infant underwent successful reimplantation of the coronary artery onto the ascending aorta and surgical closure of the septal defect. Normalization of the left ventricular function was observed at the 2-year follow-up assessment.


Radiotherapy Utilization for Patients Over Age 60 With Early Stage Breast Cancer.
Recent studies have questioned the relative benefit of radiotherapy (RT) for older patients with favorable breast cancer given the lack of survival benefit and marginal local control benefit. Despite the 2004 National Comprehensive Cancer Network (NCCN) guidelines advocating for the option of hormonal therapy alone, trends in utilization rates of RT in this group are not well-documented. We analyzed our institutional experience with implementation of the guidelines over time. We identified 564 patients aged ≥ 60 years with favorable breast cancer treated with breast conserving surgery from 2000 to 2017. Patients met criteria for Cancer and Leukemia Group B (CALGB) 9343, Postoperative Radiotherapy in Minimum Risk Elderly (PRIME II), or the very-low risk cohort identified in the Toronto-British Columbia study. Multivariable logistic regression analysis was performed to assess the magnitude of association between omission status, grade, and tumor size while controlling for age and year of diagnosis. Overall RT omission rates were 17.6% prior to the 2004 NCCN update and 45% after the publication of the 10-year CALGB data in 2013. The overall RT omission rate was 29%. Patients with grade 1 to 2 histology (odds ratio, 3.2; 95% confidence interval, 1.3-7.7; P = .01) and tumors < 1 cm (odds ratio, 1.60; 95% confidence interval, 0.4-0.9; P = .007) were more likely to omit RT than those with higher grade or larger tumors. We observed a slight decrease in the use of RT over time, suggesting a move towards adoption of the NCCN guidelines. There remains a fundamental need to continue to individualize breast cancer care based on risk stratification and make evidenced-based treatment recommendations with equitable use of health care resources.


Respiratory depression at birth--value of Apgar score and ventilatory measurements in its detection.
The purpose of this investigation was to determine the value of ventilatory measurements and Apgar score in the diagnosis of respiratory depression in the newborn infant. The following were the results of the determinations made in 24 neonates whose mothers had received meperidine in a total dose up to 3 mg/kg within three hours prior to delivery; Respiratory rate, 51+/-3.7/minute; tidal volume, 21.4 +/- 1.5 ml; minute ventilation, 339 +/- 24 ml/kg X minute; end tidal CO2, 40.8 +/- 1.3 mm Hg; ventilatory response to CO2, 21.8 +/- 2.7 ML/KG X minute X mm Hg PACO2. The mean Apgar score was 7.1 and 9.0 at 1 and 5 minutes, respectively. None of the determinations were indicative of respiratory depression with the exception of the slope of the CO2 response curve; it was considered to be below the normal range. No correlations existed between the CO2 response curve and any other values. It is concluded that meperidine administered to mothers in labor in the described dose will not significantly alter Apgar score, VE, VT, RR, AND PAco2 in the newborn infant. The extent of respiratory center depression could be determined only by the decreased ventilatory response to CO2.


A Learning Framework for Personalized Random Utility Maximization (RUM) Modeling of User Behavior.
Understanding user behavior is crucial for the success of many emerging applications that aim to provide personalized services for target users, such as many patient-centered health apps and transportation apps. Models based on the random utility maximization (RUM) theory are widely used in learning and understanding behavioral preferences on the population level but find difficult to estimate individuals' preferences, particularly when individuals' data are limited and fragmented. To address this problem, our framework builds on the concepts such as canonical structure and membership vectors invented in recent works on collaborative learning and is suitable for modeling heterogeneous population with insufficient data from each individual. We further propose an extension of the collaborative learning framework using pairwise-fusion regularization as a knowledge discovery tool for real-world applications where the canonical structure is uneven, e.g., some canonical models may only represent minor subpopulations. Computationally competent algorithms are developed to solve the corresponding optimization challenges. Extensive simulation studies and a real-world application in smart transportation demand management (TDM) show the effectiveness of our proposed methods.


Tissue reaction to silver nanoparticles dispersion as an alternative irrigating solution.
Nanomaterials have been used to create new consumer products as well as applications for life sciences and biotechnology. The aim of this study was to evaluate the tissue response to implanted polyethylene tubes filled with fibrin sponge embedded with silver nanoparticles dispersion. Thirty rats received individually 4 polyethylene tubes filled with sponge embedded in 47 ppm, 23 ppm silver nanoparticles dispersion, 2.5% sodium hypochlorite, or with no embedding as control. The observation periods were 7, 15, 30, 60, and 90 days. After each period of time, 6 animals were killed, and the tubes and surrounding tissue were removed, fixed, and prepared to be analyzed in light microscope with glycol methacrylate embedding, 3-μm serial cutting, and hematoxylin-eosin stain. Qualitative and quantitative evaluations of the reactions were performed. Both materials caused moderate reactions at 7 days. The response was similar to the control on the 15th day with 23 ppm silver nanoparticles dispersion and 2.5% sodium hypochlorite and on the 30th day with 47 ppm silver nanoparticles dispersion. It was possible to conclude that silver nanoparticles dispersion was biocompatible especially in a lower concentration.


[Multimodality therapy concept in stage I-IIIA small cell bronchial carcinoma. Case follow-up over 15 years].
We analysed our results of multimodal therapy including chemotherapy, radiotherapy and surgery in 150 consecutive patients with SCLC stage I-IIIa operated on in our hospital between 1983 and 2000. Median age: 58 years, stages see Table 2. Patients with proven SCLC had induction chemotherapy prior to surgery. All patients received three cycles of adjuvant chemotherapy, some with additional radiotherapy. Perioperative mortality: 2%. Median survival: 22.4 months. R0 resection was possible in 84% of all patients. Pre- and post-surgery staging differed in the majority of the patients. Rotes of 1-, 2- and 5-year survival were 79%, 47%, and 32%, respectively. A median survival of 22.4 months in multimodally treated LD-SCLC, most of them stage IIb/IIIa appears promising. Randomized studies based on clinical staging procedures are not recommended. Survival data are promising.


Clinical assessment of extracellular fluid volume in hyponatremia.
Assessment of the status of extracellular fluid volume is important in evaluating the cause and selecting appropriate therapy for hyponatremic disorders. Since the sensitivity and specificity of clinical assessment of extracellular fluid volume status in hyponatremic states remain unknown, 58 non-edematous patients with serum sodium less than 130 meq/liter were prospectively evaluated. Patients were judged to be either normovolemic (no response of serum sodium to saline infusion) or hypovolemic (saline infusion significantly corrected hyponatremia). Hypovolemic patients had significantly higher plasma renin activity (5.0 +/- 1.5 versus 2.5 +/- 0.5 ng/ml per three hours, p less than 0.05) and norepinephrine (1,054 +/- 252 versus 519 +/- 55 pg/ml, p less than 0.05) concentrations than did normovolemic patients. Clinical assessment correctly identified only 47 percent of hypovolemic patients and 48 percent of normovolemic patients. Thus, clinical assessment was of limited sensitivity and specificity in identifying extracellular fluid volume status in these hyponatremic patients. However, the concentration of sodium in a spot urine sample clearly separated hypovolemic (mean UNa = 18.4 +/- 3.1 meq/liter) from normovolemic (mean UNa = 72 +/- 3.7 meq/liter, p less than 0.001) hyponatremic patients.


Is tranexamic acid safe for the hip joint?
To show the effects of tranexamic acid, which is a drug frequently used to control bleeding, on the hip joint and sciatic nerve in animal experiments. There were 15 rats in each of the 3 groups, with a total of 45 rats. Topical saline injections were applied to the first group, topical TXA injections to the second group, and intravenous (IV) TXA injections to the third group. In the samples taken from the hip joint 3 weeks later, femoral head cartilage, sciatic nerve, and joint capsule thicknesses were analyzed histologically. Statistically significantly more cartilage degradation was detected in the femoral head cartilage in both the IV and intraarticular TXA group when compared to the control group. The groups were also compared in terms of acetabular cartilage; however, no histological difference was found between the groups. It was seen that when the femoral head cartilage thickness (the average of the measurements made from 3 different points were used) was examined, the cartilage thickness in the topical TXA group was less when compared to the other 2 groups. However, this difference was determined to not be statistically significant. The data of the hip joint capsule thickness measurement, it was found that the capsule thickness in the topical TXA applied group was less when compared to the other 2 groups. However, this difference was not statistically significant. When the sciatic nerves in all 3 groups were compared, no different staining characteristics were found in the immunofluorescence examination. TXA, which is frequently used in orthopedic practice, shows negative effects on hip joint cartilage in both topical and intravenous application.


On-treatment risk model for predicting treatment response in advanced renal cell carcinoma.
The field of immunotherapy combinations for advanced renal cell carcinoma (aRCC) has been expanded in recent years. However, the treatment response varies widely among individual patients. It is still a challenge to predict oncological outcome in clinical practice. We assessed the impact of an activated immune system reflected by changes in C-reactive protein (CRP) levels and the early onset of treatment-related adverse events (TRAEs) on the treatment response. In this retrospective analysis of 57 aRCC patients, CRP kinetics based on previous descriptions of CRP flare-response, CRP response or CRP non-response, and the TRAEs, which occurred within a month after therapy initiation, were obtained for this study. According to logistic regression analysis of both factors, we stratified the patients into risk groups: the presence of CRP flare-response/response and early onset of TRAE (low-risk group); the presence of a single factor (intermediate-risk group); and without both factors (high-risk group). Ten patients (17%) experienced primary disease progression. No progressive disease was observed in the low-risk group, while 60% (n = 6/10) of the high-risk group showed a primary disease progression. Significantly, an increased risk of disease progression was observed by patients without CRP response and TRAEs (p < 0.001). The present analysis displays the predictive value of the on-treatment risk model based on CRP kinetics and the early onset of TRAEs, which can be easy to implement in clinical practice to optimize the treatment monitoring.


Factors associated with demand for emergency medical services by people with hypertension and diabetes.
to analyze the association between recurrence of emergency service visits due to lack of blood pressure and/or glycemic control with sociodemographic variables and disease registration in Primary Care. quantitative study, which consulted medical records of people who attended these services two or more times for 26 months. Descriptive statistics and multiple logistic regression models were used in analysis. most people did not have hypertension and/or diabetes record in their Primary Care records. The absence of this record was more frequent in males, aged between 18 and 59 years, with low education and lack of blood pressure. There was association between greater number of people seeking these services in the same year and not monitoring the chronic condition in specialized care. people who do not follow up hypertension and/or diabetes in Primary Care are more likely to need assistance due to blood pressure and/or glycemic management.


The evaluation of a model speech training program for deaf children.
Systematic speech training procedures were employed with a group of 20 hearing-impaired children ranging in age from 7 to 10 years. Using a primarily auditory-oral approach, the speech training program employed a hierarchical sequence in order to teach the suprasegmental patterns of English to the children. The children's performance on the speech training hierarchy was monitored on a daily basis using a checklist system. Based on their rate of progress in the development of speech skills, the children were divided into three groups post hoc: rapid, slow but steady, inordinately slow. Although the system worked well, on the average, approximately one-third of the children encountered serious difficulites at one or more levels of the hierarchy. Examination of the children's background information and audiological data revealed that those children who encountered difficulty had an extremely limited amount of residual hearing and/or problems other than a hearing handicap.


Preferential solvation of a dicyanate ester monomer and poly(sulfone) in different organic solvents by size-exclusion chromatography.
Preferential solvation parameters A in the ternary systems solvent (1) -monomer (2) -polymer (3) were determined as a tool to measure the compatibility between the cyanate ester monomer Arocy B10 and poly(sulfone), PSF, in the presence of three organic solvents: tetrahydrofuran, dimethylformamide and dicloromethane. The A parameter was measured by size-exclusion chromatography at different monomer-to-polymer ratios. The quantitative evaluation was rigorously made at polymer-diluted conditions. PSF was found to be preferentially solvated by the monomer. Concerning the solvent used, systems containing tetrahydrofuran showed the strongest solvation, the lowest A values being those obtained in dicloromethane. These results were in accordance with the intrinsic viscosity values of the PSF-solvent systems. The variation of A values with the Arocy B10 concentration is strongly dependent upon the nature of the solvent.


Uncontrolled pain in critically ill patients and acute kidney injury: a hypothesis-generating cohort study.
In critically ill patients, acute pain occurs frequently, causes sympathetic activation, release of inflammatory mediators, and potential organ dysfunction, with the kidneys potentially sensitive to inflammation-mediated injury. This study aimed to explore the association between acute pain in critically ill patients and the occurrence of acute kidney injury (AKI). Data from a retrospective cohort of adult patients admitted between June 2013 and June 2016 to the Intensive Care Unit (ICU) of a tertiary hospital in São Paulo, Brazil, were analyzed. The main exclusion criteria were ICU length of stay < 48 h, coma, and prior kidney dysfunction. The outcome (AKI) was defined as an elevation in the baseline serum creatinine level of ≥ 0.3 mg/dl and/or > 50% at any time after the first 48 h in the ICU. Multivariable logistic regression and hierarchical cluster analysis were performed. The isolated incidence of pain was 23.6%, and the incidence of pain duration > 5 days was 10.6%. AKI occurred in 31.7% of the cohort. In multivariable logistic analysis, duration of pain > 5 days (OR 5.25 CI 2.19-12.57 p < 0.01) and mechanical ventilation (MV) ≥ 3 days (OR 5.5 CI 2.3-13.5 p < 0.01) were the variables with positive association with AKI. The hierarchical cluster analysis reinforced the relation between AKI, MV and duration of pain. Pain is an especially important issue in critically ill patients and in this exploratory study it appears to be associated with AKI development. The search for more rigorous pain control in ICU is crucial and can influence organ dysfunction.


Neuroscience: An Arousal Circuit that Senses Danger in Sleep.
Dangerous or alerting stimuli typically trigger arousal from sleep; however, the brain circuitry responsible for threat detection during sleep remains unclear. New research in mice identified a specific class of neuron in the basal forebrain that causes arousal from sleep by responding to threatening stimuli.


Lactococci dominate the bacterial communities of fermented maize, sorghum and millet slurries in Zimbabwe.
Maize, sorghum and millet fermented porridges are important as complementary foods for young children in Africa. The objective of the present study was to gain some insights into the bacterial communities of fermented slurries prepared from maize, sorghum and millets originating from different locations in Zimbabwe, and prepared either at household or laboratory level. A deep sequencing approach targeting the hypervariable V4 region of the 16S rRNA gene was used and yielded about 100,000 sequences per sample. Lactococcus dominated all the fermented slurries, flanked by other lactic acid bacteria such as Weissella, Leuconostoc and Enterococcus. Enterobacteriaceae detected in the water samples persisted throughout all the fermented cereals. Other sub-dominant bacteria identified in the fermented slurries included Aeromonas, Pseudomonas and Acinetobacter. In addition, some Proteobacteria, Actinobacteria and Bacteroidetes associated with the raw materials and environment were also detected. Fermented slurries could not be differentiated based on their origin nor on the type of fermentation, but clear differences were observed between red sorghum fermented slurries and fermented slurries prepared from other cereal flours. A thorough understanding of the functional capacities of the microbiota in African fermented slurries is highly needed in order to steer the fermentation for the production of standard, safe and nutritious fermented products.


Impact on neonatal outcome and anthropometric growth in very low birth weight infants with histological chorioamnionitis.
Chorioamnionitis (CAM) is one of the main causes of preterm labor. The specific aim of our study was to evaluate neonatal outcome and anthropometric growth at the corrected age of 2 years after exposure to an adverse intrauterine event of CAM in very low birth weight (VLBW, less than 1500 g) infants. One hundred and nineteen VLBW infants had adequate placental histological data available for the study. Maternal and perinatal characteristics and neonatal morbidity were determined. The infants were followed up prospectively and their anthropometric growth was recorded in the neonatal follow-up clinic for 2 years. Histological CAM was evident in 64 cases (53.8%, CAM group). Patients with histological CAM delivered earlier (27.8 +/- 2.9 vs. 29.6 +/- 3.6 weeks, p = 0.003), and they had higher incidence of preterm premature rupture of membranes (PPROM, p less than 0.001) and longer ventilation days (p = 0.001). After adjusting for gestational age, sepsis (aOR, 3.355), bronchopulmonary dysplasia (aOR, 3.018) and mechanical ventilation (aOR, 4.094) had a higher incidence in the CAM group. At the corrected ages of 6, 12, 18 and 24 months, anthropometric measurements, including body weight, body height and head circumference, were similar for the study and control infants. Histological CAM was associated with a higher incidence of PPROM, sepsis, bronchopulmonary dysplasia, more mechanical ventilation and longer ventilation days. However, at the age of 2 years, CAM had no impact on anthropometric growth.


Incidence and clinical outcome of Cryptococcosis in a nation with advanced HIV surveillance program.
Cryptococcosis is a major opportunistic invasive mycosis that mostly affects immunocompromised patients. This was an observational study of all culture-confirmed cases of cryptococcosis conducted in the State of Qatar from January 2005 to December 2016. Cryptococcus fungi were identified using Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS). Fourteen culture-confirmed cases of cryptococcosis were identified during the study period. Four patients had a Human Immunodeficiency Virus (HIV) infection with low CD4 count and five were receiving immunosuppressant medications. The rest of the patients were apparently immuno-competent. The central nervous system was the most common site of infection (57%) followed by bloodstream infection (36%) and pneumonia (14%). One patient had a cryptococcal scrotal infection. Twelve isolates were Cryptococcus neoformans and 2 were Cryptococcus laurentii. All isolates were within the wild type ECV values to amphotericin B and fluconazole. Only 2 patients with bloodstream infection (HIV negative) died. The rest were cured of the infection. Cryptococcosis is a rare fungal disease in the State of Qatar, mostly diagnosed in Asian immigrants. The central nervous system is the most common site of infection. The presence of the fungus in the blood carries a high mortality.


A human monoclonal IgM with autoantibody activities against heparan sulphate and the mitotic spindle.
A monoclonal IgM kappa from a patient with Waldenström's macroglobulinaemia (IgM-Rod) was found to react at temperatures below 28 degrees C with all tissue basement membranes and the cell coat of non-haematopoietic cells. IgM-Rod antibody was directed against heparan sulphate side chains of heparan sulphate proteoglycans as shown by binding in a solid-phase ELISA to heparan sulphate glycosaminoglycans but not to other purified subcomponents of the extracellular matrix; and by specific inhibition of the observed reactivity by heparitinase treatment. IgM-Rod showed cross-reactivity by indirect immunofluorescence with an as yet unidentified structure expressed in the nucleus during cell division and becoming associated with the mitotic spindle apparatus. The co-existence of both binding activities for heparan sulphate and nuclei determinants in the same IgM molecule was deduced from adsorption-elution experiments and from the inhibitory effect of a mouse monoclonal anti-idiotypic antibody directed against the paratope of IgM-Rod.


Feruloylated oligosaccharides and ferulic acid alter gut microbiome to alleviate diabetic syndrome.
Gut microbiome has been proven to be involved in the development of type 2 diabetes (T2D). Additionally, increasing evidence showed that the composition of gut microbiome is highly associated with the outcome of T2D therapy. Previously we demonstrated that feruloylated oligosaccharides (FOs) and ferulic acid (FA) alleviated diabetic syndrome in rats, but the detailed mechanism has not been explored yet. In this study we strived to characterize how FOs and FA altered the gut microbiome and related metabolome in diabetic rats by using high-throughput sequencing of 16S rRNA and gas chromatography (GC). Our results showed that FOs reduced the abundance of Lactobacillus, Ruminococcus, Oscillibacter, and Desulfovibrio, but increased the abundance of Akkermansia, Phascolarctobacterium and Turicibacter. The structure of gut microbiome in FOs treated rats was similar with healthy rats rather than diabetic rats. Likewise, FA decreased the portion of Lactobacillus, Ruminococcus, but promoted the growth of Bacteroides, Blautia, Faecalibacterium, Parabacteroides and Phascolarctobacterium. Additionally, the short-chain fatty acids (SCFAs) and branched-chain fatty acids (BCFAs), the main bacterial lipid metabolites in gut mediating host glucose metabolism, was dramatically elevated along with FOs and FA treatment. Our findings indicated that FOs and FA attenuated diabetic syndrome in rats most likely by modulating the composition and metabolism of gut microbiome. The study gives new insight into the mechanism underlying the anti-diabetes effect of functional foods as well as facilitates the development of dietary supplements for diabetic patients.


Imaging of pericardial tumours: a case report.
Pericardial tumours are unusual and may be difficult to characterise with imaging. They manifest as large, non-contractile, solid masses within the pericardium. Presenting symptoms include heart failure, arrythmias, sudden death, cyanosis and chest pain. We describe a case of massive pericardial fibroma in a 52 year old woman, who presented with palpitations only. We illustrate the different imaging modalities available to image this tumour prior to surgical resection, and indicate the strengths and weaknesses of each.


Evaluation of mixed-mode chromatographic resins for separating IgG from serum albumin containing feedstock.
Mixed-mode chromatography has been focused as a cost-effective new technique for antibody purification. In this study, four mixed-mode resins with N-benzyl-N-methyl ethanol amine, 2-benzamido-4-mercaptobutanoic acide, 4-mercapto-ethyl-pyridine and phenylpropylamine as the ligands were tested and the multi-functional interactions between ligand and protein were discussed. Immunoglobulin G (IgG), bovine serum albumin (BSA) and the binary mixture of BSA and IgG were used as the model feedstock to compare the separation behaviors by pH gradient elution. The comparison analysis showed mixed-mode resin with N-benzyl-N-methyl ethanol amine as the ligand had the best ability to separate IgG and BSA. The results indicated that for four resins tested ionic interaction might play the dominant role in the separation of IgG and BSA while the hydrophobic interactions and hydrogen bonding have some subsidiary effects. The pH stepwise elution and sample loading were optimized to improve the IgG purification from serum albumin containing feedstock. High purity (92.3%) and high recovery (95.6%) of IgG were obtained. The results indicated that mixed-mode chromatography would be a potential option for antibody purification with the control of loading and elution conditions.


Evaluation of the function of polymorphonuclear neutrophils in patients with glomerulonephritis. I. Influence of nitrogen metabolites retention, in renal failure on functional activity of polymorphonuclear neutrophils.
The function of polymorphonuclear neutrophils in two groups of patients with glomerulonephritis was investigated. Patients were divided according to renal efficiency. In the group of 37 patients with renal failure a decrease in chemotactic activity, phagocytal index and iodination activity of leukocytes was observed (as compared with the control group). Our data indicate that renal insufficiency has some influence on the activity of polymorphonuclear neutrophils.


Present and future innovations in radiation oncology.
The purpose of this article is to provide a review of innovations in radiation oncology that have been recently adopted as well as those that are likely to be adopted in the near future. Physics and engineering innovations, including image-guidance technologies and charged particle therapy, are discussed. Biologic innovations, including novel radiation sensitizers, functional imaging for use in treatment planning, and altered fractionation, are also discussed.


Synthesis of fluorescent organic nano-dots and their application as efficient color conversion layers.
Efficient conversion of light from short wavelengths to longer wavelengths using color conversion layers (CCLs) underpins the successful operation of numerous contemporary display and lighting technologies. Inorganic quantum dots, based on CdSe or InP, for example, have received much attention in this context, however, suffer from instability and toxic cadmium or phosphine chemistry. Organic nanoparticles (NPs), though less often studied, are capable of very competitive performance, including outstanding stability and water-processability. Surfactants, which are critical in stabilizing many types of nano-structures, have not yet been used extensively in organic NPs. Here we show the utility of surfactants in the synthesis and processing of organic NPs by thoroughly characterizing the effect of ionic and non-ionic surfactants on the properties of fluorescent organic NPs. Using this information, we identify surfactant processing conditions that result in nearly 100 % conversion of organic fluorophores into sub-micrometer particles, or nano-dots, with outstanding performance as CCLs. Such water dispersions are environmentally benign and efficiently convert light. They can be used for a range of fluorophores covering a full spectral gamut, with excellent color purity, including full-width at half-maximum (FWHM) values as low as 21 nm. Compared to inorganic (InP) reference CCLs, the organic nano-dot based CCLs show superior color conversion efficiency and substantially improved long-term stability.


Design of iron chelators: syntheses and iron (III) complexing abilities of tripodal tris-bidentate ligands.
The interest in synthetic siderophore mimics includes therapeutic applications (iron chelation therapy), the design of more effective agents to deliver Fe to plants and the development of new chemical tools in order to study iron metabolism and iron assimilation processes in living systems. The design of ligands needs a rational approach for the understanding of the metal ion complexing abilities. The octahedral arrangement of donor atoms is the most favourable geometry, allowing the maximum possible distance between their formal or partial negative charges. Hexadentate chelators, usually of the tris-bidentate type, can accommodate the metal coordination sphere and are well-suited to obtain high pFe values. The first part of this review is dedicated to selected synthetic routes, taking into account (i) the nature of the chelating subunits, connecting groups and spacers, (ii) the water-solubility and hydrophilic/lipophilic balance, (iii) the chirality and (iv) the possibility of grafting probes or vectors. In the second part, we discuss the role of the molecular design on complexing abilities (thermodynamics and kinetics). The bidentate 8-hydroxyquinoline moiety offers an alternative to the usual coordinating hydroxamic acids, catechols and/or alpha-hydroxycarboxylic acids groups encountered in natural siderophores. The promizing results obtained with the tris-hydroxyquinoline-based ligand O-TRENSOX are summarized. O-TRENSOX exhibits a high and selective affinity for Fe(III) complexation. Its efficiency in delivering Fe to plants, iron mobilization, cell protection, and antiproliferative effects has been evidenced. Other chelators derived from O-TRENSOX (mixed catechol/8-hydroxyquinoline ligands, lipophilic ligands) are also described. Some results question the relevance of partition coefficients to foresee the activity of iron chelators. The development of probes (fluorescent, radioactive, spin labelled) based on the O-TRENSOX backbone is in progress in order to get insights in the complicated iron metabolism processes.


Comparative Analysis of Fascia Lata and Cartilage Graft in Revision Type 1 Tympanoplasty.
To evaluate graft epithelialization and hearing outcome in type 1 revision tympanoplasty using fascia lata and cartilage as graft material. In this study 33 revision cases of dry central perforations were divided into two groups, group 1 (n = 21) in which cartilage was used as a graft and group 2 (n = 12) in which fascia lata was used. Group 1 patients were divided according to the technique used as group 1a (n = 16) cartilage perichondrium composite island graft and group 1b (n = 5) cartilage butterfly inlay graft. Patients were followed up for at least 12 months postoperatively, mean 15.63 (± 4.21) months. Outcome among the two groups were measured and compared in terms of graft epithelization and hearing improvement measured as the difference between pre and post operative mean air bone gap (ABG) at 1 year. The graft epithelialization of group 1 was 85.72% (87.5% group 1a/80% group 1b) and of group 2, 83.34%. Statistically no significant difference was found in the success rate between the two groups (p = 0.6). No significant difference was found in the hearing outcome as well (p = 0.44). The overall hearing improvement was significant in both groups (p = < 0.001) including the sub groups 1a and 1b separately. 21 out of 33 patients (63.63%) operated had a mean postoperative ABG of 20 db or less. The results of cartilage and fascia lata as graft are comparable in terms of graft epithelialization and hearing outcome in revision tympanoplasty.


Contusion Rodent Model of Traumatic Brain Injury: Controlled Cortical Impact.
Traumatic brain injury (TBI) is a heterogeneous brain injury which represents one of the leading causes of mortality and disability worldwide. Rodent TBI models are helpful to examine the cellular and molecular mechanisms after injury. Controlled cortical impact (CCI) is one of the most commonly used TBI models in rats and mice, based on its consistency of injury and ease of implementation. Here, we describe a CCI protocol to induce a moderate contusion to the somatosensory motor cortex. We provide additional protocols for monitoring animals after CCI induction.


Surgical workflow for fully navigated high sacral amputation in sacral chordoma.
The method of choice for treatment of sacral chordomas is en bloc tumor removal via sacrectomy or sacral amputation in varying degrees depending on the initial tumor extent. Besides local tumor control, the preservation of neurological function is equally important to minimize postoperative bladder and bowel dysfunction. Removal of sacral tumors is complicated by the complex regional anatomy of the pelvis and the surrounding visceral and retroperitoneal structures. We aim to describe the surgical workflow for a fully navigated high sacral amputation facilitated by integration of an intraoperative computed tomography (iCT)-based spinal navigation system. An iCT-based spinal navigation system (AIRO® CT scanner, Brainlab AG, Feldkirchen, Germany) was used to perform intraoperative navigation with an image-guidance system and infrared tracking camera (BrainLab CurveTM, Brainlab AG, Feldkirchen, Germany) in combination with the spinal navigation set by Brainlab (Brainlab AG, Feldkirchen, Germany) to perform a fully navigated high sacral amputation. We demonstrate the successful implementation of iCT-based spinal navigation during high sacral amputation and the key advantages of this technique throughout the surgery. iCT-based spinal navigation is a useful complementing technique for en bloc high sacral amputations that renders the surgery safer and more accurate.


Stimulation of vaginal growth and cornification in the absence of estrogen or nuclear binding of the estrogen receptor.
Mechanical stimulation of the vagina in ovariectomized rats results in vaginal epithelial proliferation and cornification which is identical to that seen with estradiol benzoate treatment. The estrogen receptor is localized primarily in the cytosol of mechanically stimulated vaginae, whereas, after estradiol benzoate treatment, the receptor is found in the nuclear compartment. Thus, it is possible to obtain a biological response ordinarily controlled by estrogen without the involvement of either the hormone or its receptor.


Activation of ganglion cells in wild-type and P23H rat retinas with a small subretinal electrode.
Electronic retinal prostheses are being developed for people who become blind due to loss of photoreceptors from the disease retinitis pigmentosa. Previously, we reported on the responses of RGCs in the P23H rat (a model of retinitis pigmentosa) and the Sprague-Dawley (SD) rat to stimulation with a 400-μm diameter electrode (Jensen and Rizzo, 2011). With recent clinical trials now utilizing smaller (50-200 μm) electrodes, I sought to investigate the electrically evoked responses of RGCs in P23H and SD rat retinas with a smaller (125-μm diameter) electrode. Here, I report on the electrically evoked spike activity from RGCs that arose from stimulation of the retinal neural network. With biphasic current pulses of 1 ms per phase, the thresholds for activation of SD rat RGCs ranged from 0.52 to 2.8 μA; thresholds of P23H rat RGCs ranged from 1.2 to 7.8 μA. Median thresholds of RGCs were 1.4 μA in SD rats and 2.5 μA in P23H rats. These thresholds measurements were obtained with the recording electrode placed over the stimulating electrode. I also examined how thresholds of RGCs change as a function of distance (100-500 μm) from the center of the stimulating electrode. The median threshold currents of RGCs were much higher in P23H rats for all distances. What was striking was that the thresholds for activation of RGCs in P23H rat retinas rose much more rapidly. When the recording electrode was only 100-200 μm from the center of the stimulating electrode, the median threshold current of P23H rat RGCs rose by 460%. In contrast, the median threshold current of SD rat RGCs increased only 29%. I also investigated the contribution of photoreceptors to the electrically evoked responses of ON-center RGCs in SD rat retinas by examining the change in RGC thresholds when photoreceptor input to ON bipolar cells was blocked with the mGluR6 antagonist CPPG. At 500-600 μm, CPPG suppressed the light-evoked responses of the RGCs and at the same time increased the amount of current needed to generate an electrically evoked response. Similar to what was observed with SD rat RGCs, CPPG suppressed the light-evoked responses of ON-center P23H rat RGCs. However, the stimulation thresholds were not significantly altered. In conclusion, the data show that the threshold currents for indirect stimulation of both SD and P23H rat RGCs with a 125-μm diameter electrode are much lower than what we found previously with a 400-μm diameter electrode. To achieve high resolution vision with a multielectrode array, the spread of activation of RGCs needs to be limited. Our findings indicate that the spread of activation of RGCs is more confined in the degenerate retina. Lastly, my findings indicate that photoreceptors contribute to the lower stimulation thresholds of RGCs in normal, healthy retinas.


Perceived motion of contrast-modulated gratings: predictions of the multi-channel gradient model and the role of full-wave rectification.
The paper examines the perception of motion in contrast-modulated sine-wave grating patterns. These non-rigid motion patterns give rise to a spatially-structured motion percept in which perceived speed varies with spatial position. We measured the perceived motion of the low contrast regions of amplitude-modulated gratings as a function of the carrier frequency, the carrier speed, the shape of the modulation signal and the modulation depth. We found that for static carriers perceived speed was greatest in the low contrast regions of the display. The speed of the low contrast regions was underestimated and perceived speed decreased as the spatial frequency of the carrier increased. When the direction of the motion of the carrier was opposite to that of the contrast modulation, the low contrast regions could appear to be stationary. The perceived speed of the contrast modulation increased with modulation depth. The brightness contrast of the carrier grating had little effect on perceived speed of contrast-modulated patterns for average contrasts of over 10%. A motion model which had full-wave rectification as an explicit pre-processing stage followed by low-pass filtering or some other selection criterion, would predict that the motion of contrast-modulated gratings should appear rigid and that the motion of the envelope should be judged correctly. The Multi-channel Gradient Model however predicts both the structured motion field experienced when viewing these second-order motion patterns and the reductions in perceived speed as a function of carrier spatial frequency and carrier speed.


Enzymic preparation of dioxygen-18 labelled leukotriene E4 and its use in quantitative gas chromatography-mass spectrometry.
A simple and rapid method is described for the preparation of a stable isotope oxygen-18 labelled leukotriene E4 (LTE4). Oxygen-18 labelling of LTE4 methyl ester in oxygen-18 water catalysed by a pig liver esterase resulted in the incorporation of two oxygen-18 atoms in the carboxylic group of LTE4 to the extent of 89.8% ([18O2]LTE4) and one oxygen-18 atom to the extent of 9.4% ([16O18O]LTE4), with only 0.7% remaining unchanged ([16O2]LTE4). [18O2]LTE4 was found not to back-exchange following incubation in acidified urine (pH 4.0) at 4 degrees C for up to 20 h. [18O2]LTE4 was demonstrated to be a useful internal standard in a method for the quantitative determination of LTE4 in human urine involving high-performance liquid chromatography and gas chromatography with negative-ion chemical ionization tandem mass spectrometry: the concentration of LTE4 in a 24-h urine sample of a healthy subject was determined to be 68.1 pg/ml.


Asymmetrical competition between the bell miner (Manorina melanophrys, Meliphagidae) and other honeyeaters: evidence from Southeastern Victoria, Australia.
The Bell Miner (Manorina melanophrys, Meliphagidae) is a medium-sized, colonial and co-operatively breeding honeyeater. Recent works show that the Bell Miner presents clear patterns of interspecific competition involving aggressive behaviour against many honeyeaters (Meliphagidae) and other bird species (Loyn et al. 1983; Clarke 1984). Nevertheless, those works have been based on short-term (1 year or less) studies only, and none of them have studied the effect territorial defence has on Bell Miners' fitness. We show how the population of honeyeaters decreased over 7 years at the Sir Colin Mackenzie Zoological Park (Southeastern Victoria, Australia). The decrease of honeyeaters in the study site was correlated with a local increase in the Bell Miner population which has been expanding since at least 1983. This process presumably led to the spatial zonation of Bell Miners and honeyeaters observed at present, while other passerine species show no sensitivity to either the invasion of Bell Miners in the recent past or to the present spatial distribution of the Bell Miner population. Finally, we show that Bell Miner reproductive activity is not affected by their interaction with competitors, which leads us to conclude that the interaction between the Bell Miner and other honeyeaters would be better described as asymmetrical competition.


Analysis of Volatile Esters and Alkanoic Acids by an Atmospheric Pressure Corona Discharge Ionization Collision-Induced Dissociation Mass Spectrometry in Positive-Ion Mode: Ionization, Fragmentation Patterns, and Discrimination between Isomeric Compounds.
The ionization and fragmentation patterns of 24 compounds with elemental composition of CmH2mO2, including isomeric esters and alkanoic acids, were investigated by atmospheric pressure corona discharge ionization collision-induced dissociation (CID) mass spectrometry in the positive-ion mode. All compounds were ionized as protonated molecules and NH4+ adducts. In addition, fragment ions were observed in mass spectra of esters other than methyl esters, which are owing to the dissociation of the alkyl group in the alcohol side from the protonated molecules. In CID spectra, protonated alkanoic acids/methyl esters split off H2O/CH3OH and CO or the alkyl group in the acid side, depending on the carbon chain length. Protonated esters (other than methyl esters) mainly fragmented the alkyl group in the alcohol side. These general rules on ionization and fragmentation patterns can provide relevant information on the discrimination of isomers.


A noble electrochemical sensor based on TiO2@CuO-N-rGO and poly (L-cysteine) nanocomposite applicable for trace analysis of flunitrazepam.
Flunitrazepam or date rape medication with trade name of Rohypnol belongs to the benzodiazepines branch that is used as a sedative, anesthetic, anticonvulsant, muscle relaxant, and antianxiety drug. It is known as "drug of aggression" because of its very strong and long-lasting effects on the central nervous system. The sedative influence of flunitrazepam drug increases with alcohol drinking, which causes mental and motor disorders and causes the victim to become silent. Due to its criminals use, its accurate measurement is crucial. In this work, a novel electrochemical sensor based on TiO2@CuO-N doped rGO, TiO2@CuO-N-rGO, nano-composite and poly (L-cysteine), poly (L-Cys), is presented for trace analysis of flunitrazepam in aqueous solution. At first, TiO2@CuO-N-rGO nano-composite was synthesized by the sol-gel method and characterized by Raman spectroscopy, Fourier transform infrared, field emission scanning electron microscope, and X-ray diffraction analysis. Then, the suspension of the TiO2@CuO-N-rGO nano-composite was drop casted on the surface of the glassy carbon electrode (GCE/TiO2@CuO-N-rGO). After that, electro-polymerization of l-cysteine on the GCE/TiO2@CuO-N-rGO surface was performed by cyclic voltammetry (CV) method. The electrochemical characteristics of the GCE/TiO2@CuO-N-rGO/poly (L-Cys) surface were evaluated in the solution of ferri/ferrocyanide by electrochemical impedance spectroscopy (EIS) and CV techniques. The increase in current, change in oxidation peak potential, and the appearance of two reduction peaks indicated higher electron transfer rate with well-performed electrochemical process of flunitrazepam at the modified electrode surface compared to the bare GCE. These improvements originate from the synergistic effect of TiO2@CuO-N-rGO nano-composite and poly (L-Cys). Finally, a linear relationship was resulted between the oxidation peak current and the concentration of flunitrazepam in the wide concentration range of 1 nM to 50 μM with a detection limit of 0.3 nM.


Properties of the lectin from the hog peanut (Amphicarpaea bracteata).
An N-acetyl-D-galactosamine-specific lectin has been isolated from the two seed forms of the hog peanut (Amphicarpaea bracteata) using an affinity support containing the synthetic type A blood group trisaccharide alpha-D-GalNAc-(1,3)-[alpha-L-Fuc-(1,2)]-beta-D-Gal (Synsorb A). The affinity-purified lectin appears to be identical in both seed types. Gel filtration on Sephadex G-200 gives a single symmetrical peak corresponding to Mr 135,000. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis shows four subunit forms, each of which contains carbohydrate. Limited amino terminal sequencing indicates heterogeneity in two of the first 10 residues. The lectin contains no cysteine. There are four equivalent, noninteracting GalNAc binding sites per 135,000-Da molecule, having an association constant for methyl N-acetyl-alpha-D-galactosaminide of 4.0 X 10(4) M-1. Precipitin and hapten inhibition studies show the lectin to be specific for terminal, nonreducing D-GalNAc units, with a preference for the alpha-anomer and enhanced specificity for the disaccharide, GalNAc alpha 1,3GalNAc. There is also a single adenine binding site per Mr 135,000 lectin molecule with an association constant of 1.3 X 10(6) M-1.


Substance use and abuse among senior medical students in 23 medical schools.
The current study represents the first large-scale study of substance use and abuse among 2,046 senior medical students at 23 nationally distributed medical schools. With the exception of alcohol and tranquilizers, medical students use less of all such substances than do age-related cohorts from the general population.


Validity of the Holmes-Wright lantern as a color vision test for the rail industry.
A simulated field test was designed to determine whether the Holmes-Wright A lantern (HWA) is a valid color vision test for the rail industry. The simulation replicated viewing rail signal lights at 0.8 km distance under daylight conditions. Using the worst-normal as the maximum number of allowable errors on the simulation, 94% of the color-defectives failed both tests on the first trial and 92% failed at the second session. The HWA had a higher false negative rate than a false alarm rate. The majority of individuals who had discrepancies on the two tests were mild deutans. Results from the Ishihara test were marginally better at predicting performance on the simulation.


Heterogeneous Catalytic Oxidation of Amides to Imides by Manganese Oxides.
Herein, we report a one-step peroxide mediated heterogeneous catalytic oxidation of amides to imides utilizing a series of manganese oxides. Among them, Cs/Mn2O3 was found to be the most active catalyst for the selective partial oxidation of N-benzylbenzamide to diphenyl imide. We have been able to apply an optimized oxidation method to other aromatic substrates. The feasibility of using air as an oxidant, the heterogeneous nature, inexpensive catalytic materials, respectable turnover numbers, and chemoselectivity to imides make this methodology an attractive choice for functional group transformations of amides to imides.


Using interpretable boosting algorithms for modeling environmental and agricultural data.
We describe how interpretable boosting algorithms based on ridge-regularized generalized linear models can be used to analyze high-dimensional environmental data. We illustrate this by using environmental, social, human and biophysical data to predict the financial vulnerability of farmers in Chile and Tunisia against climate hazards. We show how group structures can be considered and how interactions can be found in high-dimensional datasets using a novel 2-step boosting approach. The advantages and efficacy of the proposed method are shown and discussed. Results indicate that the presence of interaction effects only improves predictive power when included in two-step boosting. The most important variable in predicting all types of vulnerabilities are natural assets. Other important variables are the type of irrigation, economic assets and the presence of crop damage of near farms.