Roles for the methylation of phosphatidylethanolamine.
The methylation of phosphatidylethanolamine is an auxiliary pathway for phosphatidylcholine biosynthesis in liver. Two forms of the enzyme, phosphatidylethanolamine N-methyltransferase, which catalyses this reaction, are located on the endoplasmic reticulum and mitochondria-associated membranes. Both forms are encoded by a single murine gene, Pempt, located on chromosome 11. The expression of the gene begins at birth. An inverse relationship exists between the rate of liver growth and the expression of phosphatidylethanolamine N-methyltransferase. However, disruption of the Pempt gene does not alter liver growth in mice or cause any other obvious phenotype.


Sleep but not hyperventilation increases the sensitivity of the EEG in patients with temporal lobe epilepsy.
To evaluate the relative impact of 3 and 5 min of hyperventilation (HV) and different sleep stages on the sensitivity of the interictal EEG in focal epilepsy. We examined 20 patients with temporal lobe epilepsy (TLE, 85%) or extratemporal epilepsy during EEG-monitoring. We compared 6 min EEG (12 epochs of 30s) during/after each: (a) waking; (b) 5 or 3 min of HV; (c) sleep stages 1, 2, 3/4 and REM regarding the frequency of epileptiform discharges (ED). The Wilcoxon matched pairs signed rank test was used. The main endpoint was the comparison of 5 min of HV with sleep stage 2. During sleep stage 2, ED were more frequent than during/after 5 min of HV (P=0.002). Compared to the waking EEG, all NREM-sleep stages activated ED. Sleep stage 2 was associated with the strongest activation. There was no difference between the waking state and REM-sleep. Compared to the waking EEG, neither 3 nor 5 min of HV showed an activation of ED. In patients with TLE, sleep stage 2 shows a significantly higher sensitivity for ED than 5 min of HV. Compared to the waking EEG, HV showed no activating effect on ED. These results suggest that in patients with the clinical diagnosis of TLE (and possibly other focal epilepsies) measures to record sleep stage 2 (such as sleep deprivation) should be increased whereas HV appears to be dispensable in this setting.


Detection of antibodies against pre-S1 proteins in sera of patients with hepatitis B virus infection by ELISA using a pre-S fusion protein expressed in E. coli.
To evaluate the importance of antibodies directed against pre-S1 proteins (anti-pre-S1) of hepatitis B virus (HBV) in human sera, an enzyme-linked immunosorbent assay (ELISA) for their detection in human sera was established, using a bacterially synthesized pre-S1 fusion protein. Using this ELISA, it was found that anti-pre-S1 was present in sera from 10 of 11 patients with acute HBV infection who recovered completely, but only present in 1 of 8 patients where the infection was prolonged. In chronic HBV carriers anti-pre-S1 was present in only 3 out of 8 patients and titers were low. In addition, in 5 out of 17 individuals who had recovered from previous HBV infection, anti-pre-S1 was also detected. Individuals immunized with recombinant HBsAg-vaccine and healthy controls were all negative for anti-pre-S1. It is suggested that presence of anti-pre-S1 in sera of patients with acute HBV infection correlates with rapid recovery.


Study on the expression of nerve growth associated protein-43 in rat model of intervertebral disc degeneration.
In the present work we studied the expression of nerve growth associated protein (GAP-43) in a rat model of intervertebral disc degeneration. 16 healthy adult SD rats, male or female, with an average weight 220g were selected. FluoroGold was injected in L5-L6 disc as the tracer. After 7 days, Freund's adjuvant was then injected to build model of intervertebral disc degeneration. After 1, 3, 7 and 14 days of modeling immune-histochemical method was used to detect the T13-L6 dorsal root ganglion and positive expression of GAP-43, TNF-α and IL-1 in L5-L6 intervertebral disc; RT-PCR method was used to detect GAP-43 mRNA and Western blot method was utilized to detect the expression levels of protein. In the observation group, the dorsal root ganglion, positive expression rates of GAP-43, TNF-α and IL-1, expression levels of GAP-43 mRNA and protein in the intervertebral disc at each time point were significantly higher than those in the control group, and the differences were statistically significant (P⟨0.05); the positive expression rates of GAP-43, TNF-α and IL-1, expression levels of GAP-43 mRNA and protein of the observation group reached the peak at 3d, and dropped at 7d; dorsal root ganglion reached the peak at 7d and dropped at 14d. Degenerative changes might be mediated by the abnormal high expression of GAP-43 and intervertebral disc inflammation jointly.


Artificial intelligence tool for the study of COVID-19 microdroplet spread across the human diameter and airborne space.
The 2019 novel coronavirus (SARS-CoV-2 / COVID-19), with a point of origin in Wuhan, China, has spread rapidly all over the world. It turned into a raging pandemic wrecking havoc on health care facilities, world economy and affecting everyone's life to date. With every new variant, rate of transmission, spread of infections and the number of cases continues to rise at an international level and scale. There are limited reliable researches that study microdroplets spread and transmissions from human sneeze or cough in the airborne space. In this paper, we propose an intelligent technique to visualize, detect, measure the distance of spread in a real-world settings of microdroplet transmissions in airborne space, called "COVNET45". In this paper, we investigate the microdroplet transmission and validate the measurements accuracy compared to published researches, by examining several microscopic and visual images taken to investigate the novel coronavirus (SARS-CoV-2 / COVID-19). The ultimate contribution is to calculate the spread of the microdroplets, measure it precisely and provide a graphical presentation. Additionally, the work employs machine learning and five algorithms for image optimization, detection and measurement.


Distinguishing rate-limiting electron versus H-atom transfers in Cu2O2-mediated oxidative N-dealkylations: application of inter- versus intramolecular kinetic isotope effects.
Copper-dioxygen adducts are important biological oxidants. To gain a better understanding of the underlying chemistries of such species, we report on a series of Cu2II-O2 complexes, [{CuII(MePY2)R'}2(O2)](B(C6F5)4)2 (1R') (where (MePY2)R' is a 4-pyridyl substituted bis[2-(2-(4-R'-pyridyl)ethyl]methylamine; R' = H, MeO, Me2N; Zhang, C. X.; et al. J. Am. Chem. Soc. 2003, 125, 634-635), which readily oxidize exogenous substrates. In this study, we explore the mechanism by which 1R' facilitates the oxidative N-dealkylation of para-substituted N,N-dimethylanilines (R-DMA; R = MeO, Me, H, CN). In the case of 1H, the linear free-energy correlation plot (rho = -2.1) and intramolecular deuterium kinetic isotope effect (KIEintra, using p-R-(C6H4)-N(CH3)(CD3)) profile suggest that R-DMA oxidation occurs through rate-limiting electron transfer (ET). This mechanism was further enforced by comparison of KIEintra versus the intermolecular KIE (KIEinter, using p-R-(C6H4)-N(CH3)2 versus p-R-(C6H4)-N(CD3)2). It was found that KIEinter < KIEintra, suggesting an ET process. In the case of both 1MeO and 1Me2N, the KIEintra profile and linear free-energy correlation plots (rho = -0.49 and -0.99 for 1Me2N and 1MeO with especially poor fitting for the latter) are inconclusive in distinguishing between a rate-limiting ET or hydrogen atom transfer (HAT) pathway. Comparisons of KIEinter versus KIEintra demonstrate a switch in mechanism from ET to HAT for 1Me2N and 1MeO oxidation of R-DMA as R-DMA is made less reducing. In the case of 1Me2N, MeO-DMA and Me-DMA are oxidized via a rate-limiting ET (KIEinter < KIEintra), while H-DMA and CN-DMA are oxidized through a HAT pathway (KIEinter approximately KIEintra). For 1MeO, oxidation occurs through an ET pathway for MeO-, Me-, and H-DMA (KIEinter < KIEintra), while CN-DMA is oxidized though a HAT process (KIEinter approximately KIEintra). Copper complex attributes, which may contribute to the mechanistic observations, are suggested.


[Epidemiologic data of rupture of the fibular ligament of the upper ankle joint].
Epidemical studies of fibular ligament lesions of the ankle joint lateral ligamentous lesions at the ankle joint are one of the most accidental injuries. It is necessary to bestow great care on prevention and therapy to avoid after effects. We report about 150 cases of acute injuries of the fibular ligament lesions of the ankle joint in 1987 treated by surgery and followed up to explore the cause of injury, its dimensions, the groups of patients and time of accident. Corresponding to literature sports activities were mostly the reason of accidents followed by casional accidents and industrial accidents. Mainly young people suffered from this injury preferring men. The part of reruptures was 14%. In 61.3% both Lig. fibulotal. ant. and Lig. fibulocalc. were ruptured followed by isolated rupture of the Lig. fibulotal.ant. in 32.7% of the cases.


Fixation and immunofluorescent analysis of creatine kinase isozymes in embryonic skeletal muscle.
Pectoral muscles from chicken embryos of various ages were examined with immunofluorescent and radiolabeled probes for the presence of brain-type creatine kinase (B-CK), muscle-specific creatine kinase (M-CK), muscle-specific myosin heavy chain (MHC), and cycling cells. The diffusible creatine kinase isozymes were not detectable by indirect immunofluorescence after standard histological fixation of embryonic muscle. However, a fixation procedure was devised that permitted immunodetection of the creatine kinase isozymes (particularly B-CK) in embryonic tissue from all stages of development studied. B-CK, M-CK, and MHC were all detected in post-mitotic muscle cells, but only B-CK was detected in cycling cells. Correlations between these findings and in vitro observations of a deterministic muscle lineage are discussed.


Automatic SNOMED coding.
Medical coding has become an important new industry that has originated from the field of medical informatics. Automatic coding of specimens has emerged as a way of relieving hospitals from the cost of paying professional coders and for achieving uniform coding for all specimens. Unfortunately, automatic coding, like manual coding, has numerous pitfalls. Further, the coding algorithms employed by manufacturers of automatic coders are typically proprietary. We have developed a method for automatic coding of pathology reports. Using this public domain autocoder, we have previously demonstrated that automatic SNOMED coding was superior to manual coding in several measurable categories, including the overall number of codes generated and the number of distinct code entities provided. In this report, we describe an algorithm that executes this strategy in the M-Technology environment.


SF3B4 is decreased in pancreatic cancer and inhibits the growth and migration of cancer cells.
Splicing factor 3b subunit 4, a critical component of pre-message RNA splicing complex, has been reported to play an important part in the tumorigenesis. However, the expression pattern and biological role of splicing factor 3b subunit 4 in pancreatic cancer have never been investigated. In this study, we found that both the messenger RNA ( p < 0.001) and protein level of splicing factor 3b subunit 4 were decreased significantly in pancreatic cancer specimens compared with their adjacent normal tissues. Overexpression of splicing factor 3b subunit 4 in pancreatic cancer cells inhibited cell growth and motility in vitro, while suppressing splicing factor 3b subunit 4 expression promoted the proliferation and migration of pancreatic cancer cells. In addition, splicing factor 3b subunit 4 was found to inhibit the activity of signal transducer and activator of transcription 3 signaling via downregulating the phosphorylation of signal transducer and activator of transcription 3 on a tyrosine residue at position 705. Taken together, these findings demonstrated that splicing factor 3b subunit 4 acted as a suppressive role in pancreatic cancer and indicated that restoring the function of splicing factor 3b subunit 4 might be a strategy for cancer therapy.


Crystallographic Analysis of the Catalytic Mechanism of Phosphopantothenoylcysteine Synthetase from Saccharomyces cerevisiae.
Phosphopantothenoylcysteine (PPC) synthetase (PPCS) catalyzes nucleoside triphosphate-dependent condensation reaction between 4'-phosphopantothenate (PPA) and l-cysteine to form PPC in CoA biosynthesis. The catalytic mechanism of PPCS has not been resolved yet. Coenzyme A biosynthesis protein 2 (Cab2) possesses activity of PPCS in Saccharomyces cerevisiae. Our enzymatic assays suggest that Cab2 could utilize both ATP and CTP to activate PPA in vitro. The results of isothermal titration calorimetry indicate that PPA, CTP, and ATP could bind to Cab2 individually, with PPA having the highest binding affinity. To provide further insight into the catalytic mechanism of Cab2, we determined the crystal structures of Cab2 and its complex with PPA, the reaction intermediate 4'-phosphopantothenoyl-CMP, the final reaction product PPC, and the product analogue phosphopantothenoylcystine. Except for PPA, all other ligands were generated in situ and present in the active-site pocket of Cab2. Structures of Cab2 in complex with ligands provide insight into substrates binding and its catalytic mechanism. Analysis of structures indicates that the carboxyl of PPA-moiety of ligands and the γ-amino group of Asn97 possess different conformations in these complex structures. The cysteine/cystine/serine selectivity assays for Cab2 indicate that the amino group rather than the thiol group of l-cysteine attacks the carbonyl of 4'-phosphopantothenoyl-CMP to form PPC. Based on structural and biochemical data, the catalytic mechanism of Cab2 was proposed for the first time.


Multiplex detection of functional G protein-coupled receptors harboring site-specifically modified unnatural amino acids.
We developed a strategy for identifying positions in G protein-coupled receptors that are amenable to bioorthogonal modification with a peptide epitope tag under cell culturing conditions. We introduced the unnatural amino acid p-azido-l-phenylalanine (azF) into human CC chemokine receptor 5 (CCR5) at site-specific amber codon mutations. We then used strain-promoted azide-alkyne [3+2] cycloaddition to label the azF-CCR5 variants with a FLAG peptide epitope-conjugated aza-dibenzocyclooctyne (DBCO) reagent. A microtiter plate-based sandwich fluorophore-linked immunosorbent assay was used to probe simultaneously the FLAG epitope and the receptor using infrared dye-conjugated antibodies so that the extent of DBCO incorporation, corresponding nominally to labeling efficiency, could be quantified ratiometrically. The extent of incorporation of DBCO at the various sites was evaluated in the context of a recent crystal structure of maraviroc-bound CCR5. We observed that labeling efficiency varied dramatically depending on the topological location of the azF in CCR5. Interestingly, position 109 in transmembrane helix 3, located in a hydrophobic cavity on the extracellular side of the receptor, was labeled most efficiently. Because the bioorthogonal labeling and detection strategy described might be used to introduce a variety of different peptide epitopes or fluorophores into engineered expressed receptors, it might prove to be useful for a wide range of applications, including single-molecule detection studies of receptor trafficking and signaling mechanism.


Lineage tracing of epithelial cells in developing teeth reveals two strategies for building signaling centers.
An important event in organogenesis is the formation of signaling centers, which are clusters of growth factor-secreting cells. In the case of tooth development, sequentially formed signaling centers known as the initiation knot (IK) and the enamel knot (EK) regulate morphogenesis. However, despite the importance of signaling centers, their origin, as well as the fate of the cells composing them, remain open questions. Here, using lineage tracing of distinct epithelial populations, we found that the EK of the mouse incisor is derived de novo from a group of SRY-box 2 (Sox2)-expressing cells in the posterior half of the tooth germ. Specifically, EK progenitors are located in the posterior ventral basal layer, as demonstrated by DiI labeling of cells. Lineage tracing the formed EK with ShhCreER , which encodes an inducible Cre recombinase under the control of the Sonic hedgehog promoter, at subsequent developmental stages showed that, once formed, some EK cells in the incisor give rise to differentiated cells, whereas in the molar, EK cells give rise to the buccal secondary EK. This work thus establishes the developmental origin as well as the fate of the EK and reveals two strategies for the emergence of serially formed signaling centers: one through de novo establishment and the other by incorporation of progeny from previously formed signaling centers.


Mechanism and specificity of an acyltransferase domain from a modular polyketide synthase.
Acyltransferase (AT) domains of modular polyketide synthases exercise tight control over the choice of α-carboxyacyl-CoA substrates, but the mechanistic basis for this specificity is unknown. We show that whereas the specificity for the electrophilic malonyl or methylmalonyl component is primarily expressed in the first half-reaction (formation of the acyl-enzyme intermediate), the second half-reaction shows comparable specificity for the acyl carrier protein that carries the nucleophilic pantetheine arm. We also show that currently used approaches for engineering AT domain specificity work mainly by degrading specificity for the natural substrate rather than by enhancing specificity for alternative substrates.


Reference set for performance testing of pediatric vaccine safety signal detection methods and systems.
Safety signal detection in spontaneous reporting system databases and electronic healthcare records is key to detection of previously unknown adverse events following immunization. Various statistical methods for signal detection in these different datasources have been developed, however none are geared to the pediatric population and none specifically to vaccines. A reference set comprising pediatric vaccine-adverse event pairs is required for reliable performance testing of statistical methods within and across data sources. The study was conducted within the context of the Global Research in Paediatrics (GRiP) project, as part of the seventh framework programme (FP7) of the European Commission. Criteria for the selection of vaccines considered in the reference set were routine and global use in the pediatric population. Adverse events were primarily selected based on importance. Outcome based systematic literature searches were performed for all identified vaccine-adverse event pairs and complemented by expert committee reports, evidence based decision support systems (e.g. Micromedex), and summaries of product characteristics. Classification into positive (PC) and negative control (NC) pairs was performed by two independent reviewers according to a pre-defined algorithm and discussed for consensus in case of disagreement. We selected 13 vaccines and 14 adverse events to be included in the reference set. From a total of 182 vaccine-adverse event pairs, we classified 18 as PC, 113 as NC and 51 as unclassifiable. Most classifications (91) were based on literature review, 45 were based on expert committee reports, and for 46 vaccine-adverse event pairs, an underlying pathomechanism was not plausible classifying the association as NC. A reference set of vaccine-adverse event pairs was developed. We propose its use for comparing signal detection methods and systems in the pediatric population.


Overexpression of PtrMYB119, a R2R3-MYB transcription factor from Populus trichocarpa, promotes anthocyanin production in hybrid poplar.
Anthocyanins are a group of colorful and bioactive natural pigments with important physiological and ecological functions in plants. We found an MYB transcription factor (PtrMYB119) from Populus trichocarpa that positively regulates anthocyanin production when expressed under the control of the CaMV 35S promoter in transgenic Arabidopsis Amino acid sequence analysis revealed that PtrMYB119 is highly homologous to Arabidopsis PAP1 (PRODUCTION OF ANTHOCYANIN PIGMENT1), a well-known transcriptional activator of anthocyanin biosynthesis. Independently produced transgenic poplars overexpressing PtrMYB119 or PtrMYB120 (a paralogous gene to PtrMYB119) (i.e., 35S::PtrMYB119 and 35S::PtrMYB120, respectively) showed elevated accumulation of anthocyanins in the whole plants, including leaf, stem and even root tissues. Using a reverse-phase high-performance liquid chromatography, we confirmed that the majority of the accumulated anthocyanin in our transgenic poplar is cyanidin-3-O-glucoside. Gene expression analyses revealed that most of the genes involved in the anthocyanin biosynthetic pathway were highly upregulated in 35S::PtrMYB119 poplars compared with the nontransformed control poplar. Among these genes, expression of PtrCHS1 (Chalcone Synthase1) and PtrANS2 (Anthocyanin Synthase2), which catalyze the initial and last steps of anthocyanin biosynthesis, respectively, was upregulated by up to 350-fold. Subsequent transient activation assays confirmed that PtrMYB119 activated the transcription of both PtrCHS1 and PtrANS2 Interestingly, expression of MYB182, a repressor of both anthocyanin and proanthocyanidin (PA) biosynthesis, was largely suppressed in 35S::PtrMYB119 poplars, while expression of MYB134, an activator of PA biosynthesis, was not changed significantly. More interestingly, high-level accumulation of anthocyanins in 35S::PtrMYB119 poplars did not have an adverse effect on plant growth. Taken together, our results demonstrate that PtrMYB119 and PtrMYB120 function as transcriptional activators of anthocyanin accumulation in both Arabidopsis and poplar.


Re-thinking our understanding of immunity: Robustness in the tissue reconstruction system.
Robustness, understood as the maintenance of specific functionalities of a given system against internal and external perturbations, is pervasive in today's biology. Yet precise applications of this notion to the immune system have been scarce. Here we show that the concept of robustness sheds light on tissue repair, and particularly on the crucial role the immune system plays in this process. We describe the specific mechanisms, including plasticity and redundancy, by which robustness is achieved in the tissue reconstruction system (TRS). In turn, tissue repair offers a very important test case for assessing the usefulness of the concept of robustness, and identifying different varieties of robustness.


Efficient Remote NIR-Controlled Drug Delivery Into Tumor Cells by Nanoplatform Modified with Tumoral-Acid-Cleavable Polyethylene Glycol.
Despite advances in controlled drug delivery, drug-delivery systems with controlled activatable drug release and high spatial and temporal resolution are still required. PEGylation has been extensively used to increase the circulation time of controlled drug-delivery systems, but polyethylene glycol (PEG) is unsuitable for uptake by tumor cells because it causes steric hindrance. In this study, a near-infrared (NIR)-light-regulated drug-delivery system with enhanced cellular uptake was developed using a hybrid nanoplatform (GO@Au). GO@Au modified with tumoral-acid-cleavable PEG circumvents the hindrance effect of PEG grafted onto the drug-delivery system without sacrificing the property of a long circulation time. With the application of NIR light, both GO and Au in GO@Au strongly absorb the NIR energy, leading to intense resonance, and causing the release of a significant proportion of the loaded drug. GO@Au retains most of the loaded drug without NIR. We show the feasibility of using this nanocarrier as a targeted, noninvasive remote-controlled drug-delivery system with high spatial and temporal resolution. Integrating chemotherapy and photothermal therapy functions into one system, we investigated the therapeutic effects of DOX-loaded GO@Au-PEG, with highly efficient drug loading. Our in vitro and in vivo results reveal a synergistic effect, enhancing the therapeutic effects of the drugs and reducing their adverse effects. These results highlight the great potential utility of GO@Au-PEG/DOX in the treatment of cancer.


Post-translational modifications of alpha5beta1 integrin by glycosaminoglycan chains. The alpha5beta1 integrin is a facultative proteoglycan.
Cell-fibronectin interactions, mediated through several different receptors, have been implicated in a wide variety of cellular properties. Among the cell surface receptors for fibronectin, integrins are the best characterized, particularly the prototype alpha5beta1 integrin. Using [125I]iodine cell surface labeling or metabolic radiolabeling with sodium [35S]sulfate, we identified alpha5beta1 integrin as the only sulfated integrin among beta1 integrin heterodimers expressed by the human melanoma cell line Mel-85. This facultative sulfation was confirmed not only by immunoprecipitation reactions using specific monoclonal antibodies but also by fibronectin affinity chromatography, two-dimensional electrophoresis, and chemical reduction. The covalent nature of alpha5beta1 integrin sulfation was evidenced by its resistance to treatments with high ionic, chaotrophic, and denaturing agents such as 4 M NaCl, 4 M MgCl2, 8 M urea, and 6 M guanidine HCl. Based on deglycosylation procedures as chemical beta-elimination, proteinase K digestion, and susceptibility to glycosaminoglycan lyases (chondroitinase ABC and heparitinases I and II), it was demonstrated that the alpha5beta1 heterodimer and alpha5 and beta1 integrin subunits were proteoglycans. The importance of alpha5beta1 sulfation was strengthened by the finding that this molecule is also sulfated in MG-63 (human osteosarcoma) and HCT-8 (human colon adenocarcinoma) cells.


Bilateral adult Wilms' tumor.
Bilateral Wilms' tumors in children are not uncommon but in the adult are quite rare. A two-mutation theory of oncogenesis has been proposed in which a prezygotic gene mutation and a postzygotic mutation lead to the development of Wilms' tumor. However, the recent discovery of a postzygotic deletion within the 11p13 band of chromosome 11 in adult cases of Wilms' tumor may explain the rarity of the bilateral form in later years. Early diagnosis is difficult because of the nonspecificity of signs and symptoms. Computer tomography, ultrasonography, and arteriography are important modalities in the earlier diagnosis of adult Wilms' tumor. Because of the rarity of these tumors, no definitive guidelines for treatment have emerged. However, a multidisciplinary approach incorporating surgery, chemotherapy and/or radiation therapy has been used most often but with varying success. This report documents the second case of bilateral adult Wilms' tumor presenting as perinephric hematomas which partially resolved.


Effect of cosolvent on protein stability: a theoretical investigation.
We developed a statistical thermodynamic algorithm for analyzing solvent-induced folding/unfolding transitions of proteins. The energetics of protein transitions is governed by the interplay between the cavity formation contribution and the term reflecting direct solute-cosolvent interactions. The latter is viewed as an exchange reaction in which the binding of a cosolvent to a solute is accompanied by release of waters of hydration to the bulk. Our model clearly differentiates between the stoichiometric and non-stoichiometric interactions of solvent or co-solvent molecules with a solute. We analyzed the urea- and glycine betaine (GB)-induced conformational transitions of model proteins of varying size which are geometrically approximated by a sphere in their native state and a spherocylinder in their unfolded state. The free energy of cavity formation and its changes accompanying protein transitions were computed based on the concepts of scaled particle theory. The free energy of direct solute-cosolvent interactions were analyzed using empirical parameters previously determined for urea and GB interactions with low molecular weight model compounds. Our computations correctly capture the mode of action of urea and GB and yield realistic numbers for (∂ΔG°/∂a3)T,P which are related to the m-values of protein denaturation. Urea is characterized by negative values of (∂ΔG°/∂a3)T,P within the entire range of urea concentrations analyzed. At concentrations below ∼1 M, GB exhibits positive values of (∂ΔG°/∂a3)T,P which turn positive at higher GB concentrations. The balance between the thermodynamic contributions of cavity formation and direct solute-cosolvent interactions that, ultimately, defines the mode of cosolvent action is extremely subtle. A 20% increase or decrease in the equilibrium constant for solute-cosolvent binding may change the sign of (∂ΔG°/∂a3)T,P thereby altering the mode of cosolvent action (stabilizing to destabilizing or vice versa).


Microleakage of multi-step and simplified-step bonding systems.
To measure and compare the microleakage of Class V resin composite restorations using the following three pairs of multi- and simplified-step dentin bonding systems (DBS): OptiBond vs. OptiBond FL, All-Bond 2 vs. One-Step, and Tenure vs. Tenure Quik. V-shaped cavities were prepared in the mesial and distal surfaces of 30 extracted human mandibular molars with margins in both enamel and cementum, and randomly assigned into three equal groups of 10 each. All DBSs were applied strictly following manufacturers' specifications before three incremental layers of resin composite (Pertac-Hybrid) were applied in all cavities. Specimens were stored for 7 days in 37 degrees C water, thermocycled for 300 cycles between 5 degrees C and 55 degrees C, immersed in 0.5% basic fuchsin solution for 24 hours, and embedded in resin before being sectioned longitudinally in multiple sections. Dye solution penetration at the tooth/composite interface was scored from 0 to 4 under a microscope at x100 at both enamel (E) and cementum (C) margins. Data were analyzed by Kruskal-Wallis and Mann-Whitney U tests with alpha = 0.05. OptiBond FL and One-Step showed less microleakage at the cementum margins compared to their multi-step versions. At the enamel margins Tenure Quik showed less microleakage compared to Tenure, and none of the other DBSs tested showed significant dye penetration at that interface. All DBSs showed significantly less microleakage at the enamel margins compared to the cementum margins except for OptiBond FL and One-Step that did not show any significant dye penetration at the cementum margins as well.


Measurement of pancreatic stone protein in the identification and management of sepsis.
Sepsis is a life-threatening syndrome characterized by a dysregulated host response to an infection resulting in multiple organ dysfunctions. Early diagnosis and management of sepsis is key to improve patient outcome but remains challenging. Despite extensive research, only few biomarkers have so far proven to be helpful in the diagnosis of sepsis. A novel protein biomarker, the pancreatic stone protein (PSP), is showing great promises. Several lines of evidences suggest that PSP has a higher diagnostic performance for the identification of sepsis than procalcitonin and C-reactive protein, and a strong prognostic value to predict unfavorable outcome at admission to intensive care unit. This review summarizes the current knowledge on the molecular mechanisms of PSP function and the clinical evidences available to highlight the relevance of this protein in the diagnosis and prognosis of sepsis.


Intensity-modulated radiation therapy followed by GDP chemotherapy for newly diagnosed stage I/II extranodal natural killer/T cell lymphoma, nasal type.
Extranodal natural killer (NK)/T cell lymphoma, nasal type (ENKTL) is an aggressive non-Hodgkin lymphoma and the majority of ENKTL cases are diagnosed at the localized stage. Radiotherapy in combination with chemotherapy has been used for localized ENKTL, but the optimal combination treatment modality and the best first-line chemotherapy regimen have not been defined. In this retrospective study, 44 patients with newly diagnosed, stages I/II ENKTL were enrolled and received intensity-modulated radiation therapy (IMRT, 50-56 Gy) followed by GDP (gemcitabine, dexamethasone, and cisplatin) chemotherapy. The median number of chemotherapy cycles per patient was 4 (range, 2-6 cycles). At the end of treatment, the overall response rate was 95% (42/44), including 39 patients (89%) who attained complete response. Two patients developed systemic progression after IMRT. With a median follow-up of 37.5 months, the 3-year overall survival (OS) rate and progression-free survival (PFS) rate were 85% (95% CI, 74 to 96%) and 77% (95% CI, 64 to 91%), respectively. Locoregional and systemic failure rates for this treatment were 9% (4/44) and 14% (6/44), respectively. The most common grades 3 to 4 adverse events included leukopenia (37%), neutropenia (34%), and mucositis (25%). No treatment-related deaths were observed. This study suggested high efficacy and low toxicity of IMRT followed by GDP regimen chemotherapy for newly diagnosed stage I/II ENKTL patients. These results require further investigation in prospective trials.


Photographic techniques of concern in metric bite mark analysis.
In bite mark analysis concern is expressed for the need to improve the precision in photographic evidence collection procedures. The use of a rigid ruler (which meets federal specifications) for scale, proper camera positioning in relation to the scale, and a method to evaluate the distortion in a two-dimensional print that records a three-dimensional object is suggested. Disregarding these factors makes metric bite mark analysis inappropriate.


An infrared filter radiometer for atmospheric cluster-ion detection.
Motivated by the detection of infrared absorption bands from atmospheric cluster ions in laboratory experiments, a narrowband filter radiometer has been constructed for ion detection in the atmosphere. It uses a filter centered at 9.15 mum wavelength with 5% bandwidth, protected by a diamond-like-carbon coated germanium auxiliary filter, and fitted to a standard pyrradiometer. A sensitivity of (29.3+/-0.1) microV/(W m(-2)) has been determined in a laboratory calibration using a blackbody source. Atmospheric experiments show that the filter radiometer, when used with a stable, low-noise amplifier, can respond to cluster-ion fluctuations. The filter radiometer's sensitivity to atmospheric ion changes is (0.47+/-0.05) (mW m(-2))/(ions cm(-3)).


Effect of glutamine-enriched total parenteral nutrition on small intestinal gut-associated lymphoid tissue and upper respiratory tract immunity.
Our prior work shows that total parenteral nutrition (TPN) causes small intestinal gut-associated lymphoid tissue (GALT) atrophy, lowers small intestinal immunoglobulin A (IgA) levels, and impairs secretory IgA-mediated mucosal immunity of the upper respiratory tract. These experiments examine whether an isonitrogenous 2% glutamine-enriched TPN solution prevents these changes. Institute of Cancer Research mice were randomized to chow (chow), intravenous feeding of a TPN solution (TPN), or glutamine-enriched TPN (glutamine) groups. After mice were fed for 5 days, lymphocytes were isolated from Peyer's patches, the intraepithelial layer, and lamina propria to determine cell yields and phenotypes. Total small intestinal IgA levels were analyzed by means of enzyme-linked immunosorbent assay. In a second series of experiments, mice underwent intranasal inoculation with H1N1 virus to establish immunity. After 3 weeks mice were randomized to chow, TPN, or glutamine groups. After feeding for 5 days, mice were rechallenged with intranasal virus and killed at 40 hours to determine viral shedding from the upper respiratory tract. Total lymphocyte yield in the Peyer's patches, the intraepithelial layer, and lamina propria, small intestinal IgA levels, and the CD4+/CD8+ ratio in the lamina propria decreased with TPN but remained normal with glutamine. On rechallenge, 87% of the mice in the TPN group shed virus in nasal secretions, whereas only 38% of the glutamine-treated group (p < 0.05 versus TPN) and 7.1% of the chow group (p < 0.002 versus TPN) were virus positive. Isonitrogenous supplementation of TPN with 2% glutamine improves IgA-mediated protection in the upper respiratory tract and normalizes GALT populations.


Computer-assisted detection of nocturnal leg motor activity in patients with restless legs syndrome and periodic leg movements during sleep.
To assess the performance of a new method for automatic detection of periodic leg movements during sleep. Leg movements during sleep were visually detected in the tibialis anterior muscles recordings of 15 patients with restless legs syndrome and 15 normal controls. Leg movements were detected automatically by means of a new computer method with which electromyogram signals are first digitally band-pass filtered and then rectified; subsequently, the detection of leg movements is performed by using 2 thresholds: one for the starting point and another to detect the end point of each leg movement. Sensitivity and false-positive rate were obtained; the American Sleep Disorders Association parameters were also computed, and the results analyzed by means of the Kendall W coefficient, the linear correlation coefficient and the Bland-Altman plots. N/A. Fifteen patients with restless legs syndrome and periodic leg movements and 15 controls. High values of the Kendall W coefficient of concordance between automatic and visual analysis were found with values close to 1 and the linear correlation coefficient for leg movements index and total leg movements index was > 0.950 (p < .000001). The Bland-Altman plots provided the limits of agreement between visual and computer detection, which were -9.01 and +9.89 for the periodic leg movement index. None of the normal controls was found to have periodic leg movement indexes >5 after automatic analysis. Our method can be applied to the clinical evaluation of periodic leg movements during sleep, with some caution in patients with a low periodic leg movement indexes. Large-scale research application is possible and can be considered as reliable.


Josiphos-Type Binaphane Ligands for Iridium-Catalyzed Enantioselective Hydrogenation of 1-Aryl-Substituted Dihydroisoquinolines.
Convenient synthesis and useful application of a series of Josiphos-type binaphane ligands were described. The iridium complexes of these chiral diphosphines displayed excellent enantioselectivity and good reactivity in the asymmetric hydrogenation of challenging 1-aryl-substituted dihydroisoquinoline substrates (full conversions, up to >99% ee, 4000 TON). The use of 40% HBr (aqueous solution) as an additive dramatically improved the asymmetric induction of these catalysts. This transformation provided a highly efficient and enantioselective access to chiral 1-aryl-substituted tetrahydroisoquinolines, which were of great importance and common in natural products and biologically active molecules.


Safety and clinical effects of EVP-6124 in subjects with Alzheimer's disease currently or previously receiving an acetylcholinesterase inhibitor medication.
Alzheimer's disease (AD) is a prevalent and currently incurable brain disease whose impact will continue to rise as the population ages. With limited treatment options, a variety of experimental therapies are currently in clinical trials. EVP-6124 (encenicline) is an α7 nicotinic acetylcholine receptor partial agonist under investigation for the symptomatic treatment of AD. EVP-6124 activates the α7 nicotinic acetylcholine receptor at low nanomolar brain concentrations and improves memory performance in rats. Treatment with EVP-6124 in Phase I and II trials involving patients with mild-to-moderate AD was well tolerated and showed statistically significant improvements compared with placebo on cognitive and functional measures. Two Phase III trials under the title COGNITIV AD will assess the efficacy and tolerability of EVP-6124 in patients with mild-to-moderate AD. Based on the completed clinical trials and proposed mechanism of action, EVP-6124 would appear to be a good candidate for therapy in combination with cholinesterase inhibitors.


Sirtuin 1 Activator SRT1720 Protects Against Lung Injury via Reduction of Type II Alveolar Epithelial Cells Apoptosis in Emphysema.
In chronic obstructive pulmonary disease (COPD), two major pathological changes that occur are the loss of alveolar structure and airspace enlargement. Type II alveolar epithelial cells (AECII) play a vital role in maintaining alveolar homeostasis and lung tissue repair. Sirtuin 1 (SIRT1), a NAD(+)-dependent histone deacetylase, regulates many pathophysiological processes including inflammation, apoptosis, cellular senescence and stress resistance. The main aim of this study was to investigate whether SRT1720, a pharmacological SIRT1 activator, could protect against AECII apoptosis in rats with emphysema caused by cigarette smoke exposure and intratracheal lipopolysaccharide instillation in vivo. During the induction of emphysema in rats, administration of SRT1720 improved lung function including airway resistance and pulmonary dynamic compliance. SRT1720 treatment up-regulated the levels of surfactant protein (SP)A, SPC, SIRT1 and forkhead box O 3, increased SIRT1 activity, down-regulated the level of p53 and inhibited AECII apoptosis. Lung injury caused by emphysema was alleviated after SRT1720 treatment. SRT1720 could protect against AECII apoptosis in rats with emphysema and thus could be used in COPD treatment.


A morphometric study of the aortomitral valve apparatus in the embryonic and adult chicken heart. Implications on the developmental hypotheses of the transposition of the great arteries.
A comparative morphometric study was performed on the aortomitral valve apparatus of the embryonic and adult chicken hearts. It was found that the thickness of the aortic and mitral valve cusps diminishes dramatically as the embryo matures, however the relative length of the aortic valve, mitral valve and subaortic conus remains constant. A comparison of the aortomitral valve apparatus in chicken and man revealed that the subaortic conus is not completely resorbed in the fowl, whereas this process is well documented in the mammalian hearts. The implications of this observation on "the differential conal growth hypothesis" of transposition of the great arteries are discussed.


Spreading dynamics in networks under context-dependent behavior.
In some systems, the behavior of the constituent units can create a "context" that modifies the direct interactions among them. This mechanism of indirect modification inspired us to develop a minimal model of context-dependent spreading. In our model, agents actively impede (favor) or not diffusion during an interaction, depending on the behavior they observe among all the peers in the group within which that interaction occurs. We divide the population into two behavioral types and provide a mean-field theory to parametrize mixing patterns of arbitrary type-assortativity within groups of any size. As an application, we examine an epidemic-spreading model with context-dependent adoption of prophylactic tools such as face masks. By analyzing the distributions of groups' size and type-composition, we uncover a rich phenomenology for the basic reproduction number and the endemic state. We analytically show how changing the group organization of contacts can either facilitate or hinder epidemic spreading, eventually moving the system from the subcritical to the supercritical phase and vice versa, depending mainly on sociological factors, such as whether the prophylactic behavior is hardly or easily induced. More generally, our work provides a theoretical foundation to model higher-order contexts and analyze their dynamical implications, envisioning a broad theory of context-dependent interactions that would allow for a new systematic investigation of a variety of complex systems.


Targeting Mycobacterium tuberculosis iron-scavenging tools: a recent update on siderophores inhibitors.
Among the various bacterial infections, tuberculosis (TB) remains a life-threatening infectious disease responsible as the most significant cause of mortality and morbidity worldwide. The co-infection of human immunodeficiency virus (HIV) in association with TB burdens the healthcare system substantially. Notably, M.tb possesses defence against most antitubercular antibiotic drugs, and the efficacy of existing frontline anti-TB drugs is waning. Also, new and recurring cases of TB from resistant bacteria such as multidrug-resistant TB (MDR), extensively drug-resistant TB (XDR), and totally drug-resistant TB (TDR) strains are increasing. Hence, TB begs the scientific community to explore the new therapeutic class of compounds with their novel mechanism. M.tb requires iron from host cells to sustain, grow, and carry out several biological processes. M.tb has developed strategic methods of acquiring iron from the surrounding environment. In this communication, we discuss an overview of M.tb iron-scavenging tools. Also, we have summarized recently identified MbtA and MbtI inhibitors, which prevent M.tb from scavenging iron. These iron-scavenging tool inhibitors have the potential to be developed as anti-TB agents/drugs.


Asarum sieboldii extracts attenuate growth, acid production, adhesion, and water-insoluble glucan synthesis of Streptococcus mutans.
Asarum sieboldii has been used in traditional folk medicine to treat dental caries and periodontal disease. In the present study, we investigated the inhibitory effect of the ethanol and aqueous extracts of A. sieboldii on the growth, acid production, adhesion, and water-insoluble glucan synthesis of Streptococcus mutans. The ethanol and aqueous extracts of A. sieboldii inhibited the growth and acid production of S. mutans. In the bacterial adherence assay, the ethanol and aqueous extracts of A. sieboldii significantly lowered the adherence of S. mutans. We also found that the ethanol and aqueous extracts of A. sieboldii significantly inhibited the synthesis of water-insoluble glucan by crude glucosyltransferase. These results suggest that A. sieboldii extracts may inhibit the caries-inducing properties of S. mutans. Further studies are necessary to clarify the active constituents of A. sieboldii extracts responsible for such biomolecular activities.


Classic Kaposi's sarcoma in two young heterosexual men.
Classic Kaposi's sarcoma is primarily a skin disease of the lower extremities affecting predominantly elderly men of Mediterranean origin. We report classic Kaposi's sarcoma first presenting in the third decade in two heterosexual, HIV-negative, males of Greek origin from Albania. Ten years after onset, the disease became aggressive with unusual clinical features that included exophytic tumors, extensive lesions on the hands as well as the legs, and prominent leg edema. One of the patients also presented lesions on the face, trunk and palate, and bubonic lymphadenopathy. In both cases, CD4 counts were normal and HLA-DR5 was positive. Treatment included radiation therapy, subcutaneous interferon (alpha-2b) and combined chemotherapy (ABV). At follow up 1 and 2 years later, both patients remain in partial remission with significant improvement in clinical disease, on maintenance interferon.


Stress-Induced (Takotsubo) Cardiomyopathy After Liver Transplant Rescued with Venoarterial Extracorporeal Membrane Oxygenation.
Here, we report the case of a 55 year old male patient without significant preexisting cardiovascular disease who received a deceased donor liver transplant. Intraoperatively, the patient developed cardiogenic shock secondary to stress-induced cardiomyopathy or Takotsubo syndrome (TTS), which was refractory to high-dose vasoactive, inotropic medical therapy. The patient was successfully managed with venoarterial extracorporeal membrane oxygenation (VA-ECMO) for 7 days, with complete recovery of cardiac function and maintenance of the hepatic graft. Given the anticipated need for only a short period of support and the expectation of full myocardial recovery, such patients may represent excellent candidates for the use of VA-ECMO.


Development of a nondestructive method for underglaze painted tiles--demonstrated by the analysis of Persian objects from the nineteenth century.
The paper presents an analytical method developed for the nondestructive study of nineteenth-century Persian polychrome underglaze painted tiles. As an example, 9 tiles from French and German museum collections were investigated. Before this work was undertaken little was known about the materials used in pottery at that time, although the broad range of colors and shades, together with their brilliant glazes, made these objects stand out when compared with Iranian ceramics of the preceding periods and suggested the use of new pigments, colorants, and glaze compositions. These materials are thought to be related to provenance and as such appropriate criteria for art-historical attribution. The analytical method is based on the combination of different nondestructive spectroscopic techniques using microfocused beams such as proton-induced X-ray emission/proton-induced gamma-ray emission, X-ray fluorescence, 3D X-ray absorption near edge structure, and confocal Raman spectroscopy and also visible spectroscopy. It was established to address the specific difficulties these objects and the technique of underglaze painting raise. The exact definition of the colors observed on the tiles using the Natural Color System helped to attribute them to different colorants. It was possible to establish the presence of Cr- and U-based colorants as new materials in nineteenth-century Persian tilemaking. The difference in glaze composition (Pb, Sn, Na, and K contents) as well as the use of B and Sn were identified as a potential marker for different workshops.


A Novel Panel of Serum Biomarkers for MPM Diagnosis.
Exposure to asbestos is the main cause of malignant pleural mesothelioma (MPM), a highly aggressive cancer of the pleura. Since the only tools for early detection are based on radiological tests, some authors focused on serum markers (i.e., mesothelin). The aim of this study was the evaluation of new serum biomarkers to be used individually or in combination, in order to improve the outcome of patients whose disease would be diagnosed at an earlier stage. Serum and plasma were available from 43 subjects previously exposed to asbestos and 27 MPM patients, all being epithelioid type. All the new markers found differentially expressed in MPM and healthy subjects, by proteomic and genomic approaches, have been validated in the serum by the use of specific ELISA. The combined approach, using tools of genomics and proteomics, is found to be highly innovative for this type of disease and led to the identification of new serum markers in the diagnosis of MPM. These results, if confirmed in a larger series, may have a strong impact in this area, because early detection of this cancer in people at high risk could significantly improve the course of the disease and the clinical approach to an individualized therapy.


Production of radioisotopes by direct electron activation.
High-energy electrons bombarded on materials can induce radioactivity by either directly knocking out neutrons or by first converting a fraction of the electron kinetic energy into electromagnetic energy, with subsequent neutron emission induced by the photons produced. The purpose of this paper was to develop a calculation method for estimating neutron emission and radionuclide production by high-energy (15-25 MeV) electrons directly interacting with a nucleus. The reaction (e,n) is considered using the method of virtual photons. The cross section for electron bombardment of lead, tantalum, rhenium, and tungsten targets is calculated. The electron cross sections are roughly 100 times less than the corresponding photon cross sections. The cross section increases monotonically with incident energy. A traveling wave linear accelerator was used for a qualitative test of the magnitude and energy dependence of the calculated cross sections. Tantalum was bombarded with electrons and the resultant emission of neutrons was inferred from the induced activation of 180Ta. The energy dependence and magnitude of the calculated electron cross sections agree with experiment within experimental uncertainties. It is concluded that accurate estimates of electron activation via the direct process is possible.


Cimetidine-induced fever.
Cimetidine is a rare cause of drug-induced fever. In a patient without evidence of hypersensitivity (the lymphocytes did not react to the drug in vitro) fever was the sole manifestation of an adverse reaction to cimetidine that was confirmed by challenge with the drug.


Two subspecies of bent-winged bats (Miniopterus orianae bassanii and oceanensis) in southern Australia have diverse fungal skin flora but not Pseudogymnoascus destructans.
Fungi are increasingly being documented as causing disease in a wide range of faunal species, including Pseudogymnoascus destructans, the fungus responsible for white nose syndrome which is having a devastating impact on bats in North America. The population size of the Australian southern bent-winged bat (Miniopterus orianae bassanii), a critically endangered subspecies, has declined over the past 50 years. As part of a larger study to determine whether disease could be a contributing factor to this decline, southern bent-winged bats were tested for the presence of a range of potentially pathogenic fungi: P. destructans, dermatophytes and Histoplasma capsulatum (a potential human pathogen commonly associated with caves inhabited by bats). Results were compared with those obtained for the more common eastern bent-winged bat (M. orianae oceanensis). All bats and their environment were negative for P. destructans. A large number of fungi were found on the skin and fur of bats, most of which were environmental or plant associated, and none of which were likely to be of significant pathogenicity for bats. A 0-19% prevalence of H. capsulatum was detected in the bat populations sampled, but not in the environment, indicative of a low zoonotic risk. Based on the results of this study, fungi are unlikely to be contributing significantly to the population decline of the southern bent-winged bat.


Management of lung nodules newly found by virtual-assisted lung mapping: a case report.
Virtual-assisted lung mapping is a novel bronchoscopic lung marking technique that uses virtual images to perform multiple concurrent dye marking of barely palpable pulmonary tumors. Subsequent chest computed tomography is required to confirm the locations marked. We here report a patient in whom computed tomography after virtual-assisted lung mapping unexpectedly revealed additional tiny pulmonary nodules. A 64-year-old woman with a history of renal cell carcinoma presented with two pulmonary nodules suspicious of metastases from renal cell carcinoma. Because we anticipated that the nodules would be difficult to palpate intraoperatively, we performed virtual-assisted lung mapping prior to attempting to resect them. Computed tomography after mapping unexpectedly detected two additional nodules. Although the existing markings did not relate to the newly found nodules, we used imaginary auxiliary lines and anatomical landmarks to extend the lung map to incorporate the unexpected nodules. The additional nodules were successfully resected by thoracoscopic wedge resection. Pathologic examination identified all nodules as metastases from renal cell carcinoma, and the surgical margins were negative. Imaginary auxiliary lines and anatomical landmarks extended the existing lung map of virtual-assisted lung mapping, enabling resection of unexpected pulmonary nodules found in post-mapping computed tomography images.


[Dissecting aneurysm of the vertebral artery--report of two cases and review of the literature].
Two cases of dissecting aneurysm of the vertebral artery are reported and the 70 cases reported previously are reviewed. Case 1 showed Wallenberg's syndrome following sudden headache on the right side without SAH. Angiograms demonstrated the "pearl and string sign" on the right vertebral artery, characteristic of a dissecting aneurysm. Through a right suboccipital craniectomy, the right vertebral artery was found to be discolored purplish-red and swollen, so the proximal vertebral artery was clipped. The postoperative course was uneventful. Case 2 showed Wallenberg's syndrome with antecedent headache. CT scan was normal and lumber puncture revealed xanthochromic CSF, which was attributed to a SAH several days before. Angiograms disclosed the "pearl and string sign" on the right vertebral artery, and right vertebral artery clipping was performed. Postoperatively it was uneventful. Intracranial dissecting aneurysms of the vertebrobasilar system are not as rare as previously thought. They can often be overlooked as fusiform aneurysms or as thrombosis associated with SAH and/or ischemic attacks. The difficulty in diagnosis, leads to a high morbidity and mortality rate. Recently many cases have been reported in sequence. These cases involving SAH were successfully treated by surgical procedure. However in addition to our cases, only two cases of successful surgical treatment after ischemic stroke, have been reported. We emphasize that surgical intervention should be carried out for dissecting aneurysms of the vertebro-basilar system, even without SAH, to prevent further dissection which could cause SAH or/and further brainstem infarction. Proximal vertebral artery occlusion is the most beneficial treatment of choice.(ABSTRACT TRUNCATED AT 250 WORDS)


Rising from the ashes: Changes in salmonid fish assemblages after 30 months of the Puyehue-Cordon Caulle volcanic eruption.
Events such as volcanic eruptions may act as disturbance agents modifying the landscape spatial diversity and increasing environmental instability. On June 4, 2011 the Puyehue-Cordon Caulle volcanic complex located on Chile (2236 m.a.s.l., 40° 02' 24" S- 70° 14' 26" W) experience a rift zone eruption ejecting during the first day 950 million metric tons into the atmosphere. Due to the westerly winds predominance, ash fell differentially upon 24 million ha of Patagonia Argentinean, been thicker deposits accumulated towards the West. In order to analyze changes on stream fish assemblages we studied seven streams 8, 19 and 30 months after the eruption along the ash deposition gradient, and compare those data to pre eruption ones. Habitat features and structure of the benthic macroinvertebrate food base of fish was studied. After the eruption, substantial environmental changes were observed in association with the large amount of ash fallout. In western sites, habitat loss due to ash accumulation, changes in the riparian zone and morphology of the main channels were observed. Turbidity was the water quality variable which reflected the most changes throughout time, with NTU values decreasing sharply from West to East sites. In west sites, increased Chironomid densities were recorded 8 months after the initial eruption as well as low EPT index values. These relationships were reversed in the less affected streams farther away from the volcano. Fish assemblages were greatly influenced both by habitat and macroinvertebrate changes. The eruption brought about an initial sharp decline in fish densities and the almost total loss of young of the year in the most western streams affecting recruitment. This effect diminished rapidly with distance from the emission center. Thirty months after the eruption, environmental changes are still occurring as a consequence of basin wide ash remobilization and transport.


Suppression of activation of signal transducer and activator of transcription-5B signaling in the vessel wall reduces balloon injury-induced neointima formation.
Previously, we have demonstrated that STAT-5B plays a role in thrombin-induced vascular smooth muscle cell (VSMC) growth and motility. To learn more about the role of STAT-5B in vessel wall remodeling, we examined its involvement in platelet-derived growth factor-BB (PDGF-BB)-stimulated VSMC growth and motility and balloon injury-induced neointima formation. PDGF-BB activated STAT-5B as measured by its tyrosine phosphorylation, DNA binding, and reporter gene activity. PDGF-BB induced cyclin D1 expression, CDK4 activity, and Rb protein phosphorylation, leading to VSMC growth and motility, and these responses were suppressed by the blockade of STAT-5B. Increased cyclin D1 levels, CDK4 activity, and Rb protein phosphorylation were observed in 1-week balloon-injured arteries compared with uninjured arteries, and these responses were also suppressed by adenovirus-mediated expression of dnSTAT-5B. In addition, adenovirus-mediated expression of dnSTAT-5B attenuated balloon injury-induced smooth muscle cell migration from media to intima and their proliferation in intima, resulting in reduced neointima formation. These observations indicate that STAT-5B plays an important role in PDGF-BB-induced VSMC growth and motility in vitro and balloon injury-induced neointima formation in vivo.


The effects of unilateral velocity-specific concentric strength training.
There is conflicting evidence regarding the efficacy of various resistance training programs for increasing strength in trained and contralateral limbs. The purposes of this investigation were to examine the effects of unilateral velocity-specific concentric isokinetic training of the extensor and flexor muscles of the elbow and knee on: 1) the carry-over effect in strength increases to velocities other than the training velocity in the trained limbs and 2) the cross-training effect at various velocities in the contralateral limbs. Twelve adult men (mean age +/- SD = 24 +/- 6 years) volunteered to train their nondominant extremities three times per week (six sets of 10 maximal repetitions) for 8 weeks at 120 degrees/sec using a Cybex II isokinetic dynamometer. The subjects were tested for increases in peak torque at 60, 120, 180, 240, and 300 degrees/sec. The training resulted in significant (p < 0.05) increases in peak torque on the trained side of the body for elbow extension and flexion as well as knee extension and flexion at all velocities tested. These findings indicated that the velocity-specific training resulted in increases in peak torque at velocities that were both greater and less than the training velocity. In addition, there was a cross-training effect, with significant (p < 0.05) increases in peak torque on the contralateral side of the body for elbow extension (all velocities except 300 degrees/sec) as well as knee extension and flexion (all velocities). These results indicate that unilateral velocity-specific concentric isokinetic training is adequate stimulus for eliciting strength gains at a wide range of velocities in both the trained and contralateral limbs.(ABSTRACT TRUNCATED AT 250 WORDS)


[Papular purpuric gloves and socks syndrome. A case report].
Papulo-purpuric gloves and socks syndrome, a typical maculopurpuric exanthema limited to hands and feet, mainly associated with Parvovirus B19 infection, has not, until now been reported in the literature in relation to pediatric cases in Italy. The case of a 10-year old girl with all the characteristics of the papulo-purpuric gloves and socks syndrome, as well as being IgM positive anti Parvovirus B19, is reported. This syndrome, despite its spontaneous remission, should be included in the differential diagnosis of maculopurpuric exanthemas.


Pembrolizumab in the treatment of metastatic non-small-cell lung cancer: patient selection and perspectives.
Lung cancer is the leading killer of both men and women in the US, and the 5-year survival remains poor. However, the approval of checkpoint blockade immunotherapy has shifted the treatment paradigm and provides hope for improved survival. The ability of non-small-cell lung cancer (NSCLC) to evade the host immune system can be overcome by agents such as pembrolizumab (MK-3475/lambrolizumab), which is a monoclonal antibody targeting the programmed death 1 (PD-1) receptor. In early studies, treatment with pembrolizumab led to dramatic and durable responses in select patients (PD-L1+ tumors). This remarkable efficacy lead to approval of pembrolizumab in the second-line setting as response rates were almost doubled compared to standard of care (SOC) chemotherapy. Most recently, data in the first-line setting from the KEYNOTE-024 study have redefined the SOC therapy for a selected subset of patients. In patients with ≥50% PD-L1+ tumors, pembrolizumab had a clear progression-free survival and overall survival benefit. Toxicity was mostly immune related and similar to checkpoint blockade toxicities observed in previous studies. The initial approval and subsequent studies of pembrolizumab required and utilized a companion diagnostic test, Dako's IHC 22C3, to assess PD-L1 status of patients. The evaluation and scoring system of this assay has been used by other companies as a reference to develop their own assays, which may complicate selection of patients. Finally, the impact of pembrolizumab in NSCLC is growing as evidenced by the numerous, ongoing trials open for combinations with chemotherapy, chemoradiation, other immunotherapeutics, immunomodulators, tyrosine kinase inhibitors, PI3K inhibitors, MEK inhibitors, hypomethylating agents, and histone deacetylase inhibitors. Further studies are also evaluating pembrolizumab in small-cell lung cancer and malignant pleural mesothelioma. This explosion of studies truly conveys the lack of therapeutic answers for lung cancer patients and the promise of pembrolizumab.


Broad-Spectrum, Potent, and Durable Ceria Nanoparticles Inactivate RNA Virus Infectivity by Targeting Virion Surfaces and Disrupting Virus-Receptor Interactions.
There is intense interest in developing long-lasting, potent, and broad-spectrum antiviral disinfectants. Ceria nanoparticles (CNPs) can undergo surface redox reactions (Ce3+ ↔ Ce4+) to generate ROS without requiring an external driving force. Here, we tested the mechanism behind our prior finding of potent inactivation of enveloped and non-enveloped RNA viruses by silver-modified CNPs, AgCNP1 and AgCNP2. Treatment of human respiratory viruses, coronavirus OC43 and parainfluenza virus type 5 (PIV5) with AgCNP1 and 2, respectively, prevented virus interactions with host cell receptors and resulted in virion aggregation. Rhinovirus 14 (RV14) mutants were selected to be resistant to inactivation by AgCNP2. Sequence analysis of the resistant virus genomes predicted two amino acid changes in surface-located residues D91V and F177L within capsid protein VP1. Consistent with the regenerative properties of CNPs, surface-applied AgCNP1 and 2 inactivated a wide range of structurally diverse viruses, including enveloped (OC43, SARS-CoV-2, and PIV5) and non-enveloped RNA viruses (RV14 and feline calicivirus; FCV). Remarkably, a single application of AgCNP1 and 2 potently inactivated up to four sequential rounds of virus challenge. Our results show broad-spectrum and long-lasting anti-viral activity of AgCNP nanoparticles, due to targeting of viral surface proteins to disrupt interactions with cellular receptors.


Musculoskeletal injuries.
In 2007-2009, BEACH (Bettering the Evaluation and Care of Health) recorded 979 encounters at which a possible sports related injury was managed in a patient aged 5-24 years. Although there is no way of determining the cause of an injury through BEACH data, we selected musculoskeletal injuries which could be caused by a sporting activity, excluding problems that were said to be work related, and limited the sample by the age of patient.


A Biomechanical Comparison of Screw and Plate Fixations for Scaphoid Fractures.
Background Headless screw fixation is the current gold standard of surgical repair for scaphoid fractures. However, maintaining reduction of certain types of scaphoid fractures is challenging with a compression screw. Plate fixation may offer superior fixation in some scaphoid fractures, particularly those with comminution, nonunion, segmental bony defects, and osteopenic or osteoporotic bone. Purpose This study questions whether method of fixation is a determinant in load to failure in segmental scaphoid fractures, and whether any fixation provides a greater mechanical advantage in simulated normal versus osteoporotic bone. Materials and Methods Polyurethane models were fashioned to simulate scaphoids with 3-mm segmental defects. Defects were bridged by one of three constructs: a locking plate, a nonlocking plate, or a headless compression screw. Three models for each fixation construct were tested for both simulated normal and osteoporotic bone density. Load to failure was recorded as the load at which the 3-mm segmental defect was closed. Results Gap closure occurred in all trials. In simulated normal bone, there were no statistically significant differences in load to failure between fixation methods. In simulated osteoporotic bone, the locking plate had a 28% greater load to failure as compared with screw fixation. Conclusion While biomechanical testing shows that plate and screw fixations are equivalent in normal density bone for fixation of a segmental scaphoid defect, locking plates are superior to screw fixation in simulated osteoporotic bone models. Clinical Relevance Plate fixation may provide superior fixation for complex scaphoid fractures, particularly in osteopenic bone.


Morphological and quantitative aspects of the development of cytoplasmic granules in concanavalin A-stimulated normal human lymphocytes.
We have studied normal human lymphocytes stimulated by concanavalin A to determine the rate and extent of development of cytoplasmic granules. Morphological studies on stimulated lymphocytes were undertaken at the light and electron microscopic level. The percentage of T lymphocytes bearing different CD antigens (CD3, CD4, and CD8) that also contained cytoplasmic granules was also assessed. Granules were identified in a high percentage of lymphocytes bearing each of the three CD markers studied.


The Relationship Between Experiential Learning and Nursing Management Competency.
This study aimed to examine the relationship between experiential learning and nursing management competency among nurse managers (NMs) in the early years of a supervisory role. The relevance of experiential learning to the development of NMs has been explored in an effort to harvest the knowledge embedded in shared NM practice narratives. However, the relationship between experiential learning and nursing management competency has not been empirically measured. The author developed an experiential learning-based program for NMs in the initial 3 years of a supervisory role. Sixty-three NMs were enrolled. The relationship between experiential learning and nursing management competency was evaluated using multiple regression analysis after completing this program. The results of multiple regression analysis revealed a significant relationship between experiential learning and nursing management competency (P < .001). A significant relationship was identified between experiential learning and nursing management competence.


[Study of characteristics of experience in successful smoking cessation among middle-aged male workers in Japan].
To clarify the characteristics of the experience leading to successful smoking cessation and to examine the nature of smoking cessation support to capture these characteristics. Semi-structured interviews were conducted for 30-60 minutes with 14 middle-aged male workers, who smoked an average of five or more cigarettes per day, and had currently quit smoking for more than six months without any treatment. Questionnaire items included the reasons for attempting to quit smoking, the methods used, changes in feelings and situations during the smoking cessation effort, past experience of failure, and current notions. To extract labels, subcategories, categories, and core categories, a verbatim record was made and analyzed qualitatively and inductively. Overall, 683 labels, 117 subcategories, 32 categories, and 9 core categories were extracted. The core categories were indicated by 【 】 and the categories by ≪ ≫. The participants expressed 【hesitation about the challenge of quitting smoking】 and 【skepticism about remaining a smoker】 owing to changes in the society surrounding smokers, and were 【preparing to face a difficult challenge】. After commencing the challenge, the smokers were 【able to achieve success in quitting smoking】 as they continued to 【try and find ways to quit smoking that suited them】 and go through the 【battle against the urge to smoke using "my energy as a shield"】 in the midst of 【pain associated with withdrawal from cigarettes】. They were able to 【establish a way of life as a successful nonsmoker】 by continuing to quit smoking, while simultaneously experiencing 【the confusion encountered after smoking cessation】. Categories indicating relationships with others, such as 【avoiding negative images due to smoking】, 【 protecting one's pride against others】, and 【experiencing pleasure at being recognized by others】 were extracted. The results showed that 【skepticism about remaining a smoker】 was seen as a turning point in the challenge of quitting smoking. Taking an approach that leads to this feeling is important for smokers. After quitting smoking, continuous follow-up is believed to be necessary to reduce 【the confusion encountered after smoking cessation】 and continue to 【establish a way of life as a successful nonsmoker】. This study revealed that "public self-consciousness" leads to behavioral changes toward smoking cessation, suggesting the possibility of new findings.


Ethical aspects in xenotransplantation.
Ethics aims to achieve optimal human behavior. However, applied ethics depend on the cultural environment. In medicine, ethics could allow an amoral operation in a fetus or in chronically ill patients because it is new and rich in prospects for acquiring knowledge and could improve the quality of life of the patient or at least save the life. The operation itself must not be ill natured or unethical and the patient must not be misled or given false hope over the outcome. Ethics would allow us to offend the dignity of man, such as by xenotransplantation, because the wish for well being is often greater than the desire to retain dignity. Ethics in xenotransplantation must be based on the interests of the poor and unlucky patient and must aim for the good of everyone, but especially meet the patient's demands.


Lower limb venous insufficiency and tobacco smoking: a case-control study.
At the present time, no study has yet clearly established whether tobacco smoking is a risk factor of lower limb venous insufficiency. This case-control study was initiated in France to determine the possible etiologic relation between tobacco smoking and lower limb venous insufficiency. A total of 1,806 cases suffering from lower limb venous insufficiency, recruited by 460 general practitioners between April 1997 and April 1998, were matched by age and gender to 1,806 controls. Data were collected on the physical examination, medical reason for consulting, current treatments, smoking habits, and known risk factors of lower limb venous insufficiency. Conditional logistic regression for the statistical analyses was performed. Known risk factors of lower limb venous insufficiency were confirmed in the overall model: family history of venous insufficiency (odds ratio (OR) = 7.7), frequent (OR = 1.4) or regular (OR = 2.7) prolonged standing at work, heat exposure (OR = 2.0), low physical activity (OR = 1.6), and (for women) more than four pregnancies (OR = 3.4). Multivariate analysis adjusted for other risk factors showed that lower limb venous insufficiency is significantly associated with tobacco smoking (OR = 1.7 for 10-19 cigarettes/day and OR = 2.4 for 20 cigarettes/day or more; p < 0.001). These results suggest that smoking is significantly associated with lower limb venous insufficiency, in accordance with biologic data and physiopathologic mechanisms.


Prolyl oligopeptidase: a potential target for the treatment of cognitive disorders.
Prolyl oligopeptidase (POP) is a ubiquitous post-proline cleaving enzyme that is highly expressed in brain. Current knowledge about the biochemical features of POP and the pharmacological action of its specific inhibitors has indicated that POP participates in several aspects of the central nervous system (CNS), including learning, memory and mood. Furthermore, a role has been suggested for POP in pathological processes such as eating and mood disorders, hypertension and cell-cycle disturbances, in addition to its proposed connection with the neurodegenerative processes which occur in Alzheimer's, Huntington's and Parkinson's diseases. The milestones responsible for the accelerated development of POP inhibitors include the discovery that these compounds reverse memory loss in animal models of drug- or lesion-induced amnesia and the observation that the expression of POP correlates with age. Today, several POP inhibitors have already been evaluated in preclinical trials as potential drugs for the treatment of natural memory deficits that occur with aging or the pathological memory loss characteristic of Alzheimer's disease. Thus, the results that are emerging from basic research on POP function will facilitate the fine-tuning of more efficient drugs to target this protease.


A Global View on Output and Outcomes of Cataract Surgery With National Indices of Socioeconomic Development.
Cataract blindness accounts for a substantial proportion of blindness worldwide. Understanding the correlations between national levels of socioeconomic development with the quantity and quality of cataract surgery may provide insight for the prioritization and resource allocation for blindness prevention programs. The relationships between human development index (HDI), gross domestic product (GDP) per capita, and cataract surgical coverage (CSC) and visual outcome of cataract surgery were examined in a multinational study utilizing secondary data from the repository for Rapid Assessment of Avoidable Blindness (RAAB), World Health Organization, Global Burden of Disease, United Nations, and the World Bank. A total of 266 RAAB studies across 73 countries/territories were retrieved. Linear regression model results revealed strong associations of HDI with prevalence of cataract blindness (β = -7.056, P < 0.001), CSC (β = 60.808, P = 0.004), proportion of intraocular lens (IOL) implantation (β = 87.040, P = 0.001), and proportion of cases with good vision outcomes among operated eyes (β = 73.351, P < 0.001) in studies performed between 1995 and 2009. Similar associations were observed for studies performed between 2010 and 2015. In addition, countries with lower GDP per capita showed a higher rate of cataract blindness (β = -0.527, P = 0.001), lower CSC (β = 9.800, P < 0.001), lower percentage of IOL implantation (β = 6.871, P = 0.001), and fewer patients with good vision outcomes after surgery (β = 7.959, P < 0.001). After controlling survey year, country, and other factors, GDP per capita and HDI were also found to be significantly associated with CSC and visual outcomes after cataract surgery (all P < 0.05). We documented the strong associations of socioeconomic indices with quantity and quality of cataract surgery. These socioeconomic indicators should be considered as important factors for developing strategies aimed to improve worldwide cataract surgery service delivery.


Impact of Diabetes Mellitus on Survival in Patients Bridged to Transplantation with Left Ventricular Assist Devices in the United States.
Diabetes mellitus (DM) is associated with increased mortality in advanced heart failure and in patients undergoing cardiac surgery. However, its impact on outcomes in patients supported with left ventricular assist devices (LVAD) is not well established. We queried the United Network for Organ Sharing (UNOS) for all adults listed for heart transplantation and bridged with continuous-flow LVAD in the United States from 2000 to 2015. We compared the pre- and post-transplant mortality of patients with and without DM. Unadjusted and adjusted time-event analyses were performed. A total of 4,978 patients were included in this analysis, of whom 33% had DM. Mean age was 53 ± 12 years, 79% were male, and 65% were Caucasian. Compared with those without, patients with DM were older (age 52 vs. 57 years; p < 0.001), more likely to be male (78% vs. 82%; p = 0.007), smokers (52% vs. 57%; p = 0.011), obese (mean body mass index [BMI] 28 vs. 30; p < 0.00), and have ischemic cardiomyopathy (37% vs. 53%; p < 0.001). Diabetes mellitus was not associated with increased wait-list mortality (adjusted hazard ratio [HR]: 1.16 [0.88-1.53]; p = 0.30), or wait-list mortality/delisting (HR: 1.17 [0.97-1.41]; p = 0.11). Among patients who underwent transplantation, DM was associated with increased adjusted overall mortality (HR: 1.23 [1.002-1.52]; p = 0.048). One-third of patients bridged-to-transplantation with LVAD in the United States have DM. While it does not increase wait-list mortality or delisting, DM is associated with decreased post-transplantation survival.


[Study on the effect of volume expansion by 0.9% and 1.8% sodium solution on cardiac-renal reflex in rabbits].
To study the effect of volume expansion by 0.9% and 1.8% sodium solution on cardiac-renal reflex activity and the role of cardiac-renal reflex in the regulation of integrated function. 18 health pentobarbital-anaesthetized rabbits were divided evenly into 2 groups at random, bilateral sino-aortic denervation, intubated via right jugular vein to monitor CVP, left renal nerve separated and ending sectioned to record ERSNA, bilateral ureter intubated to collect urine, right femoral intubated to get blood sample. 15% of whole body blood volume of 0.9% and 1.8% sodium solution were injected via jugular vein 10 ml per minute respectively. The CVP, ERSNA, bilateral urine volume and coefficient of sodium excretion were measured before treated, during treated, one minute, five minutes and ten minutes after treated. Volume expansion by 0.9% and 1.8% sodium solution respectively resulted in the increase of CVP by 64.00% +/- 15.56% and 77.00% +/- 23.74%; the decrease of the frequency of ERSNA by 44.00% +/- 13.64% and 63.00% +/- 12.49%, the average burst time of ERSNA by 37.00% +/- 16.49% and 31.00% +/- 10.69%, the increase of average interval of ERSNA bursts by 60.00% +/- 18.38% and 68.00% +/- 27.04%; the increase of urine volume by 158.00% +/- 28.10% and 640.00% +/- 155.39% in left kidney, 192.00% +/- 32.26% and 1343.00% +/- 429.95% in the right; the increase of coefficient of sodium excretion by 132.00% +/- 35.23% and 376.00% +/- 121.72% in the left, 300.00% +/- 76.99% and 856.00% +/- 261.48% in the right. Volume expansion by different solution stimulate the receptors of cardiopulmonary and regulate the water and sodium excretion of the kidney by the cardiac-renal reflex to modulate the stabilization of blood volume.


Temperature-dependent variation in the synthesis of group-specific carbohydrate by streptococcal variant strains. I. Immunochemical studies.
A temperature-dependent alteration in the synthesis of the group-specific polysaccharide was found to occur in two "variant" streptococcal strains, A-486-Var and C 121/46/4. These strains synthesize a polysaccharide with variant immunochemical characteristics when grown at 37 degrees C. However, when these organisms are grown at lower temperatures, 22 degrees C, an enhanced synthesis of Group A carbohydrate occurs. Other variant strains show no appreciable alteration of the cell wall carbohydrate composition when grown at lower temperatures. Studies on an intermediate strain show that this organism has a propensity for the synthesis of a polysaccharide with higher glucosamine content and enhanced Group A serological reactivity when grown at 22 degrees C. Immunochemical studies performed on the carbohydrates produced by the A-486-Var at various temperatures revealed that the appearance of Group A serological reactivity at lower temperatures is due to the additional synthesis of a polysaccharide with Group A specificity along with the continued synthesis of a variant carbohydrate. This finding contrasts with data obtained on the carbohydrate produced by the intermediate organisms that appears to consist predominently of one molecule bearing dual A and variant antigenic determinants.


Duplex oligomers defined via covalent casting of a one-dimensional hydrogen-bonding motif.
Hydrogen-bonded tapes comprised of monomeric molecular precursors are used to define structural parameters for the design of related oligomers encoded with predetermined modes of assembly. Application of this "covalent casting" strategy vis-à-vis the one-dimensional H-bonding motif expressed by 2-amino-4,6-dichlorotriazine has enabled the design of high-affinity duplex molecular strands. Dimeric, trimeric, and tetrameric duplex oligomers are prepared through an iterative synthetic protocol involving sequential homologation of the oligo(aminotriazine). The mode of assembly and interstrand affinity of homologous oligomers are established in solution by (1)H NMR dilution experiments, isothermal titration calorimetry (ITC), vapor pressure osmometry (VPO), cross-hybridization experiments involving the analysis of dye-labeled strands via thin-layer chromatography (TLC), and in the solid state by X-ray crystallographic analysis. Binding free energy per unimer (-Delta G degrees/n) increases significantly upon extension from monomer to dimer to trimer, signifying a strong positive cooperative effect. Nanomolar binding affinity (K(d) = 1.44 +/- 0.50 nM) was determined for the duplex trimer by ITC in 1,2-dichloroethane at 20 degrees C. In-register duplex formation is not observed for the tetramer, which appears to adopt an alternative binding mode. These data give insight into the structural and interactional features of the oligomers required for high-affinity, high-specificity binding and define a platform for the design of second-generation systems and related duplex strands for use in nanoscale assembly.


Ca2+ levels in Daphnia hemolymph may explain occurrences of daphniid species along recent Ca gradients in Canadian soft-water lakes.
Calcium levels are declining in eastern North American and western European lakes. This widespread issue is affecting the composition of crustacean zooplankton communities, as the presence and abundance of several calcium-rich daphniid species are declining, while two other daphniids, D. catawba and D. ambigua, that apparently tolerate low calcium environments, are prospering. The physiological basis for low calcium tolerance of these daphniids is unknown. In this study the presence of one Ca-rich (D. pulicaria) and one Ca-poor (D. ambigua) daphniid species in Canadian Shield lakes is assessed in relation to lake water Ca levels. The occurrence of D. ambigua was independent of Ca levels in Ontario lakes, whereas D. pulicaria was more likely to occur in lakes with relatively more Ca. In the laboratory, D. ambigua maintained lower levels of hemolymph Ca2+ across a range of low Ca levels (0.7 to 7 mg l-1) compared with D. pulicaria. The hemolymph pH remained steady across this Ca gradient in D. ambigua while it was significantly more acidic in D. pulicaria in the two lowest Ca treatments. While Ca2+ uptake was observed adjacent to the surface of D. ambigua individuals, Ca2+ loss was observed for D. pulicaria assayed under moderately high Ca levels. Based on these observations we propose that D. ambigua is able to survive in low Ca lakes by maintaining low free ionic Ca2+ levels in the hemolymph which minimizes the Ca gradient across the body wall in low Ca water thus limiting overall Ca loss and facilitating Ca2+ uptake.


[Summary of the practice guideline 'Otitis externa' (first revision) from the Dutch College of General Practitioners].
* The practice guideline 'Otitis externa', first developed by the Dutch College of General Practitioners in 1995, has been revised and updated. * It is no longer recommended to perform a KOH test on material collected from the auditory canal in patients with otitis externa. * Eardrops that contain both acid and corticosteroids are preferred over eardrops that contain acid only. * Suitable options include acidic eardrops with hydrocortisone 1% FNA and acidic eardrops with triamcinolone acetonide 0.1% FNA at a dose of 3 drops thrice daily. * The guideline contains a detailed discussion of the ototoxicity of eardrops in patients with tympanic membrane perforation. * Management of these patients, however, remains unchanged: the preferred approach is aluminium acetotartrate eardrops 1.2% FNA.


Ultrastructural changes of the rabbit lung tissue during sensitization to antigens.
In order to specify the ultrastructure of changes induced in the rabbit lung tissue during sensitization to antigens - previously studied by conventional methods -, two groups of rabbits were weekly sensitized by intramuscular injections, the first group with complete Freund adjuvant (CFA) only, the second with CFA to which human gammaglobulin was added. Fragments from caudal lobes harvested six days after the 3rd, 4th and 5th injections were processed for electron microscopy. This investigation confirmed the general process of cell accumulation within alveolar walls, interlobular areas and bronchial subepithelial layers previously appreciated histochemically and morphometrically. The predominating cells in both rabbit groups were histiocytes (macrophages) of local and blood origin; a monocyte marginating an alveolar capillary was evidenced. In the rabbits sensitized with CFA only, histiocytes were largely accompanied by lymphocytes; between them some relationships may be ultrastructurally observed. An increased number of fibrils and fibroblasts was also seen in this group. The animals sensitized with CFA containing human gamma-globulin showed active plasmoblasts and plasma cells among histiocytes; this picture corresponded to the high increase of serum precipitins. These ultrastructural changes form the basis on which hypersensitivity reactions may be challenged experimentally and during human immune chronic lung diseases.


[The kinetics of hematopoietic cell chimerism in the early period after non-myeloablative transplantation and its clinical implications].
To analyze the kinetics of hematopoietic cell chimerism in the early period after non-myeloablative stem cell transplantation (NAST) and to investigate the correlation between molecular and hematologic assessment of engraftment or rejection. Short tandem repeat-polymerase chain reaction (STR-PCR) analysis of chimerism status was carried out in 6 patients who received NAST from HLA-matched sibling donors. In 5/6 patients, the peripheral blood samples collected on the first day after allograft infusion displayed the presence of mixed chimerism. STR-PCR analysis revealed a gradual increase of the donor-specific allelic signal which became dominant over the recipient-specific allele by day +7. On day +14, hematologic chimerisms were completely donor origin. Their molecular engraftments (ME) were detected at a median time of 6 days, preceding hematologic engraftment by a median of 5 days (P > 0.05). But the sixth patient showed more than 50% host residual cells on day +7 and had no signs of ME on day +14. It suggested that molecular monitoring of the early dynamics of chimerism after NAST could be useful in predicting engraftment, or rejection. If the engraftment was less than 50% on day +7 and failed to get ME on day +14, the graft rejection would occur.


Hybrid BCI approach to control an artificial tibio-femoral joint.
Brain-Computer Interfaces (BCIs) for disabled people should allow them to use their remaining functionalities as control possibilities. BCIs connect the brain with external devices to perform the volition or intent of movement, regardless if that individual is unable to perform the task due to body impairments. In this work we fuse electromyographic (EMG) with electroencephalographic (EEG) activity in a framework called "Hybrid-BCI" (hBCI) approach to control the movement of a simulated tibio-femoral joint. Two mathematical models of a tibio-femoral joint are used to emulate the kinematic and dynamic behavior of the knee. The interest is to reproduce different velocities of the human gait cycle. The EEG signals are used to classify the user intent, which are the velocity changes, meanwhile the superficial EMG signals are used to estimate the amplitude of such intent. A multi-level controller is used to solve the trajectory tracking problem involved. The lower level consists of an individual controller for each model, it solves the tracking of the desired trajectory even considering different velocities of the human gait cycle. The mid-level uses a combination of a logical operator and a finite state machine for the switching between models. Finally, the highest level consists in a support vector machine to classify the desired activity.


A randomized controlled trial on a nurse-led smartphone-based self-management programme for people with poorly controlled type 2 diabetes: A study protocol.
To develop and compare a nurse-led smartphone-based self-management programme with an existing nurse-led diabetes service on health-related outcomes for people with poorly controlled type 2 diabetes in Singapore. Over the past decades, Asia has emerged as the "diabetes epicentre" in the world due to rapid economic development, urbanization and nutrition transition. There is an urgent need to develop more effective care management strategies in response to this rising diabetes epidemic. A randomized controlled trial with pre- and repeated posttests control group design. A total of 128 adults with poorly controlled type 2 diabetes will be recruited from the diabetes clinic of a public acute hospital in Singapore through convenience sampling. Study participants will be randomly allocated either to the experimental group or the control group. Outcome measures will include the 10-item General Self-Efficacy Scale, 11-item Revised Summary of Diabetes Self-care Activities and 19-item Diabetes-Dependent Quality of Life. Data will be collected at three time points: baseline, 3 and 6 months from the baseline. It is expected that this programme will be an alternative offered to diabetes patients to master their self-care management skills, in addition to the existing diabetes service provided in diabetes clinics in Singapore hospitals. Furthermore, the self-supporting and less resource-intensive nature of this programme, using a smartphone application as the mode of intervention delivery, will greatly reduce nurses' direct contact time with patients and allow more time to be allocated to those who require more attention. The study has been registered with ClinicalTrials.gov. The trial registration number is NCT03088475.


The effects of different photoperiods on reproduction in the sow.
Three groups of Yorkshire sows (total of 106) were exposed to photoperiods of light:dark (LD) 24:0, 12:12 and 0:24, respectively, from d 1 postweaning to 24 h postestrus. The onset and duration of estrus, conception rate, farrowing rate and litter size were recorded. Serum concentrations of luteinizing hormone (LH), estrogen and progesterone were measured. Sows in the LD 24:0 exhibited behavioral estrus for a longer period (P less than .0001) than those in LD 12:12 (4.0 vs 2.7 d). The number of days to estrus from d 1 postweaning (5.4, 4.5 and 4.7 d, respectively), conception rate (60, 67 and 73%, respectively), farrowing rate (60, 67 and 73%, respectively) and litter size (10.6, 10.2 and 10.8, respectively) were not different (P greater than .05) for the three light regimens of 24:0, 12:12 and 0:24. Maximum serum levels of LH (5.4, 5.0 and 4.5 ng/ml, respectively) and estrogen (71.8, 63.3 and 60.4 pg/ml, respectively) were not different, nor were progesterone profile means (P greater than .05) for the sows in LD 24:0, 12:12 and 0:24. These data suggest that long photoperiods prolong manifestations of behavioral estrus in the sow.


Assessing quantitative EEG spectrograms to identify non-epileptic events.
To evaluate the sensitivity and specificity of quantitative EEG (QEEG) spectrograms in order to distinguish epileptic from non-epileptic events. Seventeen patients with paroxysmal non-epileptic events, captured during EEG monitoring, were retrospectively assessed using QEEG spectrograms. These patients were compared to a control group of 13 consecutive patients (ages 25-60 years) with epileptic seizures of similar semiology. Assessment of raw EEG was employed as the gold standard against which epileptic and non-epileptic events were validated. QEEG spectrograms, available using Persyst 12 EEG system integration software, were each assessed with respect to their usefulness to distinguish epileptic from non-epileptic seizures. The given spectrogram was interpreted as indicating a seizure if, at the time of the clinically identified event, it showed a visually significant change from baseline. Eighty-two clinically identified paroxysmal events were analysed (46 non-epileptic and 36 epileptic). The "seizure detector trend analysis" spectrogram correctly classified 33/46 (71%) non-epileptic events (no seizure indicated during a clinically identified event) vs. 29/36 (81%) epileptic seizures (seizure indicated during a clinically identified event) (p=0.013). Similarly, "rhythmicity spectrogram", FFT spectrogram, "asymmetry relative spectrogram", and integrated-amplitude EEG spectrogram detected 28/46 (61%), 30/46 (65%), 22/46 (48%) and 27/46 (59%) non-epileptic events vs. 27/36 (75%), 25/36 (69%), 25/36 (69%) and 27/36 (75%) epileptic events, respectively. High sensitivities and specificities for QEEG seizure detection analyses suggest that QEEG may have a role at the bedside to facilitate early differentiation between epileptic seizures and non-epileptic events in order to avoid unnecessary administration of antiepileptic drugs and possible iatrogenic consequences.