Reactivation of γ-globin expression using a minicircle DNA system to treat β-thalassemia.
Reactivation of fetal hemoglobin by editing the B-cell lymphoma/leukemia 11A (BCL11A) erythroid enhancer is an effective gene therapy for β-thalassemia. Using the CRISPR/Cas9 system, fetal γ-globin expression can be robustly reactivated to mitigate the clinical course of β-thalassemia. In our study, we found that the transfection efficiencies of CD34+ hematopoietic stem/progenitor cells (HSPCs) were significantly and negatively correlated with the length of plasmids and greatly affected by the linearization of plasmids. Furthermore, the transgene expression of minicircles (MC) without plasmid backbone sequences was better both in vitro and in vivo compared with conventional plasmids. Thus, MC DNA was used to deliver the cassette of Staphylococcus aureus Cas9 (SaCas9) into HSPCs, and a single-guide RNA targeting the erythroid enhancer region of BCL11A was selected. After electroporation with MC DNA, an evident efficiency of gene editing and reactivation of γ-globin expression in erythroblasts derived from unsorted HSPCs was acquired. No significant off-target effects were found by deep sequencing. Furthermore, fragments derived from lentiviral vectors, but not MC DNA, were highly enriched in promoter, exon, intron, distal-intergenic, and cancer-associated genes, indicating that MC DNA provided a relatively safe and efficient vector for delivering transgenes. The developed MC DNA vector provided a potential approach for the delivery of SaCas9 cassette and the reactivation of γ-globin expression for ameliorating syndromes of β-thalassemia.


The Association of d-Ribulose- 1,5-Bisphosphate Carboxylase/Oxygenase with Phosphoribulokinase.
When Ribulose- 1,5-bisphosphate carboxylase/oxygenase was purified from spinach leaves (Spinacia oleracea) using precipitation with polyethylene glycol and MgCl(2) followed by DEAE cellulose chromatography, 75% of phosphoribulokinase and 7% of phosphoriboisomerase activities copurified with ribulose- 1,5-bisphosphate carboxylase/oxygenase. This enzyme preparation showed ribose-5-phosphate and ribulose-5-phosphate dependent carboxylase and oxygenase activities which were nearly equivalent to its corresponding ribulose- 1,5-bisphosphate dependent activity. The ribose-5-phosphate and ribulose-5-phosphate dependent reaction rates were stable and linear for much longer time periods than the ribulose- 1,5-bisphosphate dependent rates. When sucrose gradients were used to purify ribulose- 1,5-bisphosphate carboxylase/oxygenase from crude stromal extracts, phosphoribulokinase was found to cosediment with ribulose- 1,5-bisphosphate carboxylase. Under these conditions most of the phosphoriboisomerase activity remained with the slower sedimenting proteins. Ammonium sulfate precipitation resulted in separation of the ribulose- 1,5-bisphosphate carboxylase peak from phosphoribulokinase peak. Crude extracts of peas Pisum sativum and spinach contained 0.725 to 0.730 milligram of phosphoribulokinase per milligram of chlorophyll, respectively, based on an enzyme-linked immunosorbent assay.


A tactile feedback hexapod operating robot for endoscopic procedures.
This paper describes a test prototype for precision robot-assisted surgery using a hexapod operating robot and a movable operating cockpit for tactile feedback. The objective of the work described is twofold: 1, to evaluate the use of hexapod robots for precisely manipulating endoscopes and surgical instruments in submillimeter surgery; 2, to test a new user interface concept based on tactile feedback. Based on the principle of a flight simulator, the aim is to give the surgeon motion cues in addition to the endoscope image, to assist his spatial orientation. The paper gives a detailed description of the system components and the potential applications.


Kinetic, thermodynamic, and mechanistic patterns for free (unbound) cytochrome c at Au/SAM junctions: impact of electronic coupling, hydrostatic pressure, and stabilizing/denaturing additives.
Combined kinetic (electrochemical) and thermodynamic (calorimetric) investigations were performed for an unbound (intact native-like) cytochrome c (CytC) freely diffusing to and from gold electrodes modified by hydroxyl-terminated self-assembled monolayer films (SAMs), under a unique broad range of experimental conditions. Our approach included: 1) fine-tuning of the charge-transfer (CT) distance by using the extended set of Au-deposited hydroxyl-terminated alkanethiol SAMs [-S-(CH(2))(n)-OH] of variable thickness (n=2, 3, 4, 6, 11); 2) application of a high-pressure (up to 150 MPa) kinetic strategy toward the representative Au/SAM/CytC assemblies (n=3, 4, 6); 3) complementary electrochemical and microcalorimetric studies on the impact of some stabilizing and denaturing additives. We report for the first time a mechanistic changeover detected for "free" CytC by three independent kinetic methods, manifested through 1) the abrupt change in the dependence of the shape of the electron exchange standard rate constant (k(o)) versus the SAM thickness (resulting in a variation of estimated actual CT range within ca. 15 to 25 A including ca. 11 A of an "effective" heme-to-omega-hydroxyl distance). The corresponding values of the electronic coupling matrix element vary within the range from ca. 3 to 0.02 cm(-1); 2) the change in activation volume from +6.7 (n=3), to approximately 0 (n=4), and -5.5 (n=6) cm(3) mol(-1) (disclosing at n=3 a direct pressure effect on the protein's internal viscosity); 3) a "full" Kramers-type viscosity dependence for k(o) at n=2 and 3 (demonstrating control of an intraglobular friction through the external dynamic properties), and its gradual transformation to the viscosity independent (nonadiabatic) regime at n=6 and 11. Multilateral cross-testing of "free" CytC in a native-like, glucose-stabilized and urea-destabilized (molten-globule-like) states revealed novel intrinsic links between local/global structural and functional characteristics. Importantly, our results on the high-pressure and solution-viscosity effects, together with matching literature data, strongly support the concept of "dynamic slaving", which implies that fluctuations involving "small" solution components control the proteins' intrinsic dynamics and function in a highly cooperative manner as far as CT processes under adiabatic conditions are concerned.


Strategies aimed at preventing long-term opioid use in trauma and orthopaedic surgery: a scoping review.
Long-term opioid use, which may have significant individual and societal impacts, has been documented in up to 20% of patients after trauma or orthopaedic surgery. The objectives of this scoping review were to systematically map the research on strategies aiming to prevent chronic opioid use in these populations and to identify knowledge gaps in this area. This scoping review is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) Checklist. We searched seven databases and websites of relevant organizations. Selected studies and guidelines were published between January 2008 and September 2021. Preventive strategies were categorized as: system-based, pharmacological, educational, multimodal, and others. We summarized findings using measures of central tendency and frequency along with p-values. We also reported the level of evidence and the strength of recommendations presented in clinical guidelines. A total of 391 studies met the inclusion criteria after initial screening from which 66 studies and 20 guidelines were selected. Studies mainly focused on orthopaedic surgery (62,1%), trauma (30.3%) and spine surgery (7.6%). Among system-based strategies, hospital-based individualized opioid tapering protocols, and regulation initiatives limiting the prescription of opioids were associated with statistically significant decreases in morphine equivalent doses (MEDs) at 1 to 3 months following trauma and orthopaedic surgery. Among pharmacological strategies, only the use of non-steroidal anti-inflammatory drugs and beta blockers led to a significant reduction in MEDs up to 12 months after orthopaedic surgery. Most studies on educational strategies, multimodal strategies and psychological strategies were associated with significant reductions in MEDs beyond 1 month. The majority of recommendations from clinical practice guidelines were of low level of evidence. This scoping review advances knowledge on existing strategies to prevent long-term opioid use in trauma and orthopaedic surgery patients. We observed that system-based, educational, multimodal and psychological strategies are the most promising. Future research should focus on determining which strategies should be implemented particularly in trauma patients at high risk for long-term use, testing those that can promote a judicious prescription of opioids while preventing an illicit use, and evaluating their effects on relevant patient-reported and social outcomes.


Effects of Inflammation on Hemostasis in Acutely Ill Patients with Liver Disease.
Patients with liver diseases are in a rebalanced state of hemostasis, due to simultaneous decline in pro- and anticoagulant factors. This balance seems to remain even in the sickest patients, but is less stable and might destabilize when patients develop disease complications. Patients with acute decompensation of cirrhosis, acute-on-chronic liver failure, or acute liver failure often develop complications associated with changes in the hemostatic system, such as systemic inflammation. Systemic inflammation causes hemostatic alterations by adhesion and aggregation of platelets, release of von Willebrand factor (VWF), enhanced expression of tissue factor, inhibition of natural anticoagulant pathways, and inhibition of fibrinolysis. Laboratory tests of hemostasis in acutely-ill liver patients may indicate a hypocoagulable state (decreased platelet count, prolongations in prothrombin time and activated partial thromboplastin time, decreased fibrinogen levels) due to decreased synthetic liver capacity or consumption, or a hypercoagulable state (increased VWF levels, hypofibrinolysis in global tests). Whether these changes are clinically relevant and should be corrected with antithrombotic drugs or blood products is incompletely understood. Inflammation and activation of coagulation may cause local ischemia, progression of liver disease, and multiorgan failure. Anti-inflammatory treatment in acutely-ill liver patients may be of potential interest to prevent thrombotic or bleeding complications and halt progression of liver disease.


The contribution of the perichondrium to the structural mechanical behavior of the costal-cartilage.
The costal-cartilage in the human ribcage is a composite structure consisting of a cartilage substance surrounded by a fibrous, tendon-like perichondrium. Current computational models of the human ribcage represent the costal-cartilage as a homogeneous material, with no consideration for the mechanical contributions of the perichondrium. This study sought to investigate the role of the perichondrium in the structural mechanical behavior of the costal-cartilage. Twenty-two specimens of postmortem human costal-cartilage were subjected to cantilevered-like loading both with the perichondrium intact and with the perichondrium removed. The test method was chosen to approximate the cartilage loading that occurs when a concentrated, posteriorly directed load is applied to the midsternum. The removal of the perichondrium resulted in a statistically significant (two-tailed Student's t-test, p< or =0.05) decrease of approximately 47% (95% C.I. of 35-58%) in the peak anterior-posterior reaction forces generated during the tests. When tested with the perichondrium removed, the specimens also exhibited failure in the cartilage substance in the regions that experienced tension from bending. These results suggest that the perichondrium does contribute significantly to the stiffness and strength of the costal-cartilage structure under this type loading, and should be accounted for in computational models of the thorax and ribcage.


Lipids of a sterol-nonrequiring Mycoplasma.
The lipids of the sterol nonrequiring Mycoplasma strain S743 were found to include both ester glycerophosphatides (phosphatidylglycerol, acylphosphatidylglycerol, and diphosphatidylglycerol) and ceramide glycerophosphate compounds containing N-hydroxyacyl groups. The major phosphosphingolipid was tentatively identified as a hydroxyceramidephosphorylglycerol containing an O-acyl group. These compounds became labeled during growth in the presence of (32)P-orthophosphate, (14)C-glycerol, or (14)C-palmitate. The lipid fraction also contained free long-chain base. (14)C-palmitate was converted to labeled sphinganine. The long-chain base composition of the lipids was modified by growing the organisms in media containing different fatty acids, which were converted to bases containing two more C atoms per molecule. Ninety per cent of the long-chain base from cells grown in medium supplemented with elaidate consisted of monounsaturated C(20) base.


A relationship that makes life worth-living: levels of value orientation explain differences in meaning and life satisfaction.
When people talk about their values they refer to what is meaningful to them. Although meaning is associated with life satisfaction, previous studies report inconsistent results regarding the association of values and well-being. A cross-sectional study (N = 276) addresses the research question, do values influence experiences of meaning and subjective evaluations of life satisfaction? To assess whether providing a definition of "meaningful" is necessary when employing meaning measures, we assigned participants to condition where some provided their definition and others read a definition of "meaningful". All participants described a recent meaningful experience; they characterized it with sources of meaning; they read descriptions of 10 values and assessed the degree those were relevant to their experience; and they completed meaning and life satisfaction measures. Findings, which were unaffected by reading a definition of "meaningful", indicated that the most common source of meaning (Family) was associated positively with the value of Tradition and negatively with the value of Universalism. Latent Profile Analysis identified three profiles denoting participants' level of value orientation, which explained interindividual differences in average levels of meaning and life satisfaction variables. Participants who associated their meaningful experience with the 10 universal values at a high level scored higher in the meaning and life satisfaction measures than those who associated their experience to the 10 universal values at a low level. The present work advances knowledge regarding the relationship between meaning, values and life satisfaction and validates previous studies reporting on meaning as a marker of well-being.


Cinnamaldehyde and 2-methoxycinnamaldehyde as NF-kappaB inhibitors from Cinnamomum cassia.
Nuclear factor (NF)-cB is a transcription factor regulating the expression of inflammatory and immune genes. In the present study, an extract from stem bark of Cinnamomum cassia Blume(Lauraceae) was discovered to have an inhibitory effect on LPS-induced NF-KB transcriptional activity, which was determined using macrophages RAW 264.7 transfected stably with an alkaline phosphatase reporter construct containing four copies of the NF-KB binding KB sequence. Following activity-guided fractionation, trans-cinnamaldehyde and 2-methoxycinnamaldehyde were identified as the NF-KB inhibitors from C cassia with IC50 values of 43 MM and 31 pM, respectively. As a positive control, caffeic acid phenethyl ester (CAPE) showed an IC50 value of 2 uM on NF-KB transcriptional activity. Both trans-cinnamaldehyde and 2-methoxycinnamaldehyde inhibited LPS-induced DNA binding activity of NF-KB in addition to NF-KB transcription-al activity.


The effect of fluorine-18 fluorodeoxyglucose positron emission tomography on the management of cutaneous malignant melanoma.
To assess the effect of positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose (FDG) on the treatment of patients with cutaneous malignant melanoma. We retrospectively reviewed the medical records of 38 patients with newly diagnosed (n = 25) and recurrent (n = 13) cutaneous melanoma who were referred for evaluation with FDG PET imaging at our institution. We compared the PET findings with computed tomography (CT), which was available in 21 (55%) patients, and tabulated the changes in the diagnostic evaluation and therapeutic management that were prompted by PET during a follow-up period of 10 to 36 months. Compared with PET, the extent of disease was underestimated by CT in 5 (13%) patients. Planned surgical resection of metastases was canceled in two of these patients. In another patient, surveillance PET detected an unsuspected hypermetabolic abdominal mass that was noted on a subsequent CT to arise from the small bowel. The mass was found to be jejunal metastatic melanoma at the time of resection. Overall, PET influenced surgical management in 3 (8%) patients, but it did not affect the wait-and-watch strategy or decision to initiate immunotherapy in the others. FDG PET contributes important information not provided by CT and has a substantial effect on the clinical management of patients with malignant melanoma.


Estimation of scavenging capacity of melatonin and other antioxidants: contribution and evaluation in germinated seeds.
Seven edible seeds for the levels of melatonin, phenolic compounds and their antioxidant capacity were evaluated during germination process. Radical scavenging parameters were also studied in standard antioxidants to understand their antiradical actions. Germination brought about significant increases of total phenol compounds in all edible seeds, showing red cabbage, radish and broccoli the highest contents (21.6, 20.4 and 16.4 mg GAE/g DW, respectively). The concentration of melatonin is greatly variable in edible seeds, exhibiting significant increases during germination. The highest levels were found in red cabbage (857 pg/g DW) radish (536 pg/g DW) and broccoli (439 pg/g DW). The germinated seeds which had the highest levels of polyphenols and melatonin were those that showed the most relevant antiradical activities (>97%). This information is valuable for the incorporation of red cabbage, radish and broccoli germinated seeds into the diet to promote potential health benefits.


[Effects of combined therapy of Phosphatidylinositol 3p-Kinase and Paclitaxel in human lung cancer nude mice model.].
Increasing evidence suggests that aberrant activation of PI3K/Akt is involved in many human cancers, and that inhibition of the PI3K/Akt pathway might be a promising strategy for cancer therapy. The aims of this study is to evaluate the effects of combined therapy of Phosphatidylinositol 3-Kinase inhibitor (LY294002 ) and Paclitaxel in athymic mice xenogeneic transplant model of lung cancer and to reveal the possible mechanisms involved. Eighteen athymic mice were randomly divided into 3 groups (control, paclitaxel alone and paclitaxel plus LY294002), and were treated respectively. Athymic mice xenogeneic transplant model was established by inoculation (sc) with A549 lung cancer cells. Body mass (BM) and diameter of tumor mass were measured. Furthermore, the protein expressions of CyclinD1,bcl-2 and bax in tumor tissues were analyzed with immunohistochemistry. The tumor-inhibiting rate of paclitaxel plus LY294002 (92.47%) was significantly higher than the paclitaxel alone (65.59%)(P <0.05).The protein expression of bcl-2 in paclitaxel plus LY294002 group were significantly higher, while bax was significantly lower than that in the other two groups (P <0.05). The protein expression of CyclinD1 was significantly lower than the control group (P <0.05). LY294002 can enhance the effects of paclitaxel in the treatment of lung cancer and CyclinD1, bcl-2 and bax may be involved in its inhibitory effects.


Supplemental β-carotene increases IgA-secreting cells in mammary gland and IgA transfer from milk to neonatal mice.
Mortality of neonates continues to be a major problem in humans and animals. IgA provides protection against microbial antigens at mucosal surfaces. Although β-carotene supplementation has been expected to enhance retinoic acid-mediated immune response in neonates, the exact mechanism by which β-carotene enhances IgA production is still unclear. We investigated the effect of supplemental β-carotene for maternal mice during pregnancy and lactation on IgA antibody-secreting cells (ASC) in mammary gland and guts and on IgA transfer from milk to neonatal mice. Pregnant mice were fed untreated or 50 mg/kg β-carotene-supplemented diets from 6·5 d postcoitus (dpc) to 14 d postpartum (dpp). Supplemental β-carotene increased the numbers of IgA ASC in mammary gland (P < 0·05) and ileum (P < 0·001), and also mRNA expression of IgA C-region in ileum (P < 0·05) of maternal mice at 14 dpp, but few IgA ASC were detected in mammary gland at 17·5 dpc. IgA concentration in stomach contents, which represents milk IgA level, was significantly higher (P < 0·01) in neonatal mice born to β-carotene-supplemented mothers at 7 and 14 dpp, and IgA concentration in serum, stomach contents and faeces increased (P < 0·001) drastically with age. These results suggest that β-carotene supplementation for maternal mice during pregnancy and lactation is useful for enhancing IgA transfer from maternal milk to neonates owing to the increase in IgA ASC in mammary gland and ileum during lactation.


Evaluation of homology modeling of G-protein-coupled receptors in light of the A(2A) adenosine receptor crystallographic structure.
Homology modeling of the human A(2A) adenosine receptor (AR) based on bovine rhodopsin predicted a protein structure that was very similar to the recently determined crystallographic structure. The discrepancy between the experimentally observed orientation of the antagonist and those obtained by previous antagonist docking is related to the loop structure of rhodopsin being carried over to the model of the A(2A) AR and was rectified when the beta(2)-adrenergic receptor was used as a template for homology modeling. Docking of the triazolotriazine antagonist ligand ZM241385 1 was greatly improved by including water molecules of the X-ray structure or by using a constraint from mutagenesis. Automatic agonists docking to both a new homology modeled receptor and the A(2A) AR crystallographic structure produced similar results. Heterocyclic nitrogen atoms closely corresponded when the docked adenine moiety of agonists and 1 were overlaid. The cumulative mutagenesis data, which support the proposed mode of agonist docking, can be reexamined in light of the crystallographic structure. Thus, homology modeling of GPCRs remains a useful technique in probing the structure of the protein and predicting modes of ligand docking.


PCNA Loaders and Unloaders-One Ring That Rules Them All.
During each cell duplication, the entirety of the genomic DNA in every cell must be accurately and quickly copied. Given the short time available for the chore, the requirement of many proteins, and the daunting amount of DNA present, DNA replication poses a serious challenge to the cell. A high level of coordination between polymerases and other DNA and chromatin-interacting proteins is vital to complete this task. One of the most important proteins for maintaining such coordination is PCNA. PCNA is a multitasking protein that forms a homotrimeric ring that encircles the DNA. It serves as a processivity factor for DNA polymerases and acts as a landing platform for different proteins interacting with DNA and chromatin. Therefore, PCNA is a signaling hub that influences the rate and accuracy of DNA replication, regulates DNA damage repair, controls chromatin formation during the replication, and the proper segregation of the sister chromatids. With so many essential roles, PCNA recruitment and turnover on the chromatin is of utmost importance. Three different, conserved protein complexes are in charge of loading/unloading PCNA onto DNA. Replication factor C (RFC) is the canonical complex in charge of loading PCNA during the S-phase. The Ctf18 and Elg1 (ATAD5 in mammalian) proteins form complexes similar to RFC, with particular functions in the cell's nucleus. Here we summarize our current knowledge about the roles of these important factors in yeast and mammals.


A one-step low temperature processing route for organolead halide perovskite solar cells.
Organolead trihalide perovskite solar cells based upon the co-deposition of a combined Al2O3-perovskite layer at T < 110 °C are presented. We report an average PCE = 7.2% on a non-sintered Al2O3 scaffold in devices that have been manufactured from a perovskite precursor containing 5 wt% Al2O3 nanoparticles.


Catalytic micropumps: microscopic convective fluid flow and pattern formation.
As innovations continue to be made in the fields of microfluidics and the colloidal assembly, new strategies for moving particles and fluids may be needed. Heterogeneous catalysis provides means of locally converting the stored chemical energy of fuels to mechanical energy. We report an ambient temperature stationary "pump" that generates a proton concentration gradient through the bipolar electrochemical decomposition of hydrogen peroxide on patterned silver-gold surfaces. The resulting electric field drives convective fluid flow and pattern formation of colloidal tracer particles at the microscopic level by a combination of electroosmotic and electrophoretic forces.


A shark attack treated in a tertiary care centre: Case report and review of the literature.
Although uncommon, shark attacks can lead to devastating outcomes for victims. Surgeons also face unique challenges during operative management such as exsanguination, shock, specific injury patterns and infections. This case report presents the management of a 39-year-old previously healthy female attacked by a shark while on vacation in Mexico. The patient sustained severe injuries to her left arm and her left thigh. She was transferred to a Canadian institution after ambiguous operative management in Mexico and presented with no clear antibiotic coverage and a Volkman's contracture of the left upper extremity. In total, the patient underwent four washouts of wounds, two split-thickness skin grafts, one free anterolateral thigh flap, and one free transverse rectus abdominus myocutaneous flap for the reconstruction and salvage of the left lower extremity. This article highlights the specifics of this case and describes important points in managing these devastating injuries.


The descent of testis and reason for failed descent.
Although an enormous number of theories have been proposed to explain the descent of testis, none has provided a satisfactory explanation that covers the whole spectrum. Recent evidence suggests a hitherto unrecognized mechanism. This novel explanation precisely defihes all of the factors proven to be involved in the process, and links the features associated with normal or failed descent. The gubernaculum gives rise to both smooth and striated muscles. The testis is descended through the processus vaginalis via the propulsive force generated by the muscles. Propulsion describes the risk of torsion. Failure in descent in associated with a diminution in smooth muscle content, and a decrease in sympathetic tonus that depends on androgens. Alterations in G-protein linked signaling due to differences in primary messengers resulting from changes in sympathetic and parasympathetic tonuses provide the basis for blunting of testosterone response to human chorionic gonadotropin (hCG) and the decrease in fertility, but also for the increase in the risk of malignancy.


Long-term lithium treatment and thyroid antibodies: a controlled study.
Because the role of thyroid autoimmunity in the development of lithium-induced thyroid dysfunction remains controversial, we compared the prevalence of thyroid autoantibodies in patients with affective disorders receiving long-term lithium maintenance therapy with that of age- and sex-matched controls. We conducted a cross-sectional study with 100 adult patients with major affective disorders diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, revised (DSM-III-R), who were undergoing lithium therapy for 6 months or more at a specialized lithium university clinic and 100 age- and sex-matched controls with no history of an axis I psychiatric disorder. Serum autoantibodies against thyroid peroxidase (TPOAb), thyroglobulin (TgAb) and TSH receptors (TRAb) were measured. TPOAb were found in 7 patients and 11 controls, and TgAb were found in 8 patients and 15 controls. TRAb were not found in either group. In this sample of patients with affective disorders, long-term lithium treatment did not increase the prevalence of thyroid autoimmunity.


Deamidation of RhoA glutamine 63 by the Escherichia coli CNF1 toxin requires a short sequence of the GTPase switch 2 domain.
CNF1, a toxin produced by pathogenic Escherichia coli strains, deamidates the RhoA GTP-binding protein glutamine 63 and impairs RhoGAP-mediated GTP hydrolysis resulting in RhoA permanent activation. Using peptides derived from the RhoA sequence, we found that DTAGQEDYDRL (corresponding to RhoA 59-69 residues) was the minimum RhoA-derived peptide which could be deamidated in vitro by the CNF1 catalytic domain (CNF1-Cter). Site-directed mutagenesis outside the RhoA 59-69 sequence had no influence on glutamine 63 deamidation by CNF1-Cter. RhoA proteins with substitutions L57G, D65G, Y66G, or R70G were not affected in their ability to be deamidated by CNF1-Cter, whereas this was abolished by the R68G substitution. Arginine 68 is part of the DYDRL motif that is strictly conserved in Rho, Rac, and Cdc42 but not in other small GTP-binding proteins consistent with the observation that only Rho, Rac, and Cdc42 can be modified by CNF1.


Analysis of the roles of amino acid residues in the flavoprotein tryptophan 2-monooxygenase modified by 2-oxo-3-pentynoate: characterization of His338, Cys339, and Cys511 mutant enzymes.
The flavoprotein tryptophan 2-monooxygenase catalyzes the oxidative decarboxylation of tryptophan to indoleacetamide. His338, Cys339, and Cys511 of the Pseudomonas savastanoi enzyme were previously identified as possible active-site residues by modification with 2-oxo-3-pentynoate ([G. Gadda, L.J. Dangott, W.H. Johnson Jr., C.P. Whitman, P.F. Fitzpatrick, Biochemistry 38 (1999) 5822-5828]). The H338N, C339A, and C511S enzymes have been characterized to determine the roles of these residues in catalysis. The steady-state kinetic parameters with both tryptophan and methionine decrease only slightly in the case of the H338N and C339A enzymes; the decrease in activity is greater for the C511S enzyme. Only in the case of the C511S enzyme do deuterium kinetic isotope effects on kinetic parameters indicate a significant change in catalytic rates. The structural bases for the effects of the mutations can be interpreted by identification of L-amino acid oxidase and tryptophan monooxygenase as homologous proteins.


Prophylaxis and management of stress ulcers.
Stress ulcers are located in the body and fundic part of the stomach. They occur in the majority of severely ill or injured patients, but only about 10% will bleed. The most effective prophylaxis are measures against the condition giving rise to risk factors as septicaemia, shock and malnutrition. The medical prophylaxis consists of antacids and/or histamine2-blockers. Most bleedings will stop after intensive care and medication with vasopressin particularly if risk factors can be eliminated. Gastric surgery should be the last step in the treatment of bleeding stress ulcers and then we recommend non-resectional surgery as gastric devascularisation or suture ligation of bleeding vessels.


Effector functions of a mouse IgG that lacks the entire CH1 domain. C1q binding and complement fixation in the absence of antigen.
C1q binding and complement fixation were examined of a short-chain IgG2a antibody that lacks the entire CH1 domain. This short-chain antibody has been reported to have a low level of constitutive complement-activating activity in the absence of Ag. Two-dimensional SDS/PAGE and cation-exchange chromatography have demonstrated that two types of IgG2a proteins are secreted by the short-chain IgG2a antibody producing cell line. It has been shown that 1) the difference between these two types of the IgG2a proteins is whether the two L chains are linked by a disulfide bridge or not, and 2) C1q-binding and complement-activating activities are expressed only when the inter L chain disulfide bridge does not exist. A molecular model is presented for the active form of the short-chain IgG2a antibody.


Tilting-filter measurements in dayglow rocket photometry.
A rocket-borne photometer containing two tilting-filter channels for the measurement of the [OI] lambdalambda6300-A and 5577A emission lines in the day airglow is described. The results of one flight substantiate the employment of tilting filters to determine accurate corrections for background continuum and provide reliable height profiles of emission intensity down to approximately 90 km. Discussions on the calibration of the instrument and its baffling against sunlight are also presented.


Metabolism of xenobiotics by rat-liver mitochondria: uptake of N,N-dimethyl[14C]amphetamine by rat-liver mitochondria.
Uptake of N,N-dimethyl[14C]amphetamine by freshly isolated rat-liver mitochondria was analysed using a modified Klingenberg's centrifugal layer filtration technique. Influx and efflux of the substrate occurred rapidly at room temperature. Membrane transport, probably an active process, was strongly inhibited at 0 degrees C.


Prevalence of serum galectin-1 autoantibodies in seven types of cancer: A potential biomarker.
Although serum galectin-1 antibodies (s-GAL-1-Abs) have been evaluated in a small number of patients with cancer, a large series of patients with different cancer types have not been reported. The current study evaluated 1,833 patients with esophageal cancer (n=172), gastric cancer (n=317), colorectal cancer (n=262), hepatocellular carcinoma (n=91), prostate cancer (n=358), breast cancer (n=364), lung cancer (n=269) and 72 healthy individuals. s-GAL-1-Abs levels were analyzed using an originally developed ELISA system. A cut-off optical density value was determined as the mean (0.053) + 3 standard deviations (0.105) of sera from healthy controls. The results revealed that the positive rate of s-GAL-1-Abs in patients with hepatocellular carcinoma (16.7%) and lung cancer (13.8%) were significantly higher compared with the other groups: Esophageal cancer (11.6%), colorectal cancer (11.5%), prostate cancer (7.3%), gastric cancer (6.9%), breast cancer (6.9%) and healthy controls (4.2%). Although the positive rates of s-GAL-1-Abs in different cancer types were relatively low, s-GAL-1-Abs may be useful for patients with hepatocellular carcinoma and lung cancer.


Long-term effect of an ethanol/sodium citrate locking solution on the mechanical properties of hemodialysis catheters.
To investigate the effect of a 30% ethanol/4% sodium citrate catheter locking solution on the mechanical properties of hemodialysis (HD) catheters over 36 weeks. Twenty-one HD catheters were used in this study. Three catheters, not exposed to locking solutions, underwent mechanical testing to determine baseline properties. Nine of the remaining 18 catheters were filled with normal saline and underwent mechanical testing in groups of three at 12, 24 and 36 weeks. Similarly, nine catheters were filled with the 30% ethanol/4% sodium citrate locking solution and tested in a similar manner. The average force required to break the catheter lumens tended to be smaller in the catheters exposed to 30% ethanol/4% sodium citrate compared to saline controls at 12 and 24 weeks; however, there were no statistically significant differences between the groups after 36 weeks of exposure. The forces required to break these HD catheters are magnitudes greater than forces generated during a typical HD session. We conclude that the 30% ethanol/4% sodium citrate locking solution had an effect on the mechanical properties of the catheters investigated, but not to the degree that would preclude further in vivo investigation. Further studies are necessary to determine the safety and efficacy of this catheter locking solution.


Synthesis and properties of stereoregular cyclic polysilanols: cis-[PhSi(O)OH](4), cis-[PhSi(O)OH](6), and tris-cis-tris-trans-[PhSi(O)OH](12).
New stereoregular cyclic polysilanols of the general formula [PhSi(O)OH]n (n = 6 and 12) have been selectively obtained in high yields by the reaction of cagelike oligophenylmetallasiloxanes with dilute solutions of hydrochloric acid at low temperatures. An alternative method was used to prepare cis-[PhSi(O)OH](4) from sodium phenylsiloxanolate, cis-[(Na(+))(4)[PhSi(O)O(-)](4)].(1-butanol)(x). All compounds were fully characterized by NMR and IR spectroscopy and molecular weight determinations. The structure of cis-[PhSi(O)OH](6) was confirmed by single-crystal X-ray analysis. Furthermore, a series of stereoregular cyclosiloxanes containing triorganylsiloxy groups at each silicon atom was prepared by the reactions of the cyclic polysilanols with triorganylchlorosilanes Me(3)SiCl, Me(2)ViSiCl, and Me(2)(CH(2)Cl)SiCl.


Manipulation of microparticles using phase-controllable ultrasonic standing waves.
A method of manipulating microparticles in a liquid using ultrasound is proposed and demonstrated. An ultrasonic standing wave with nodal planes whose positions are controllable by varying the relative phase of two applied sinusoidal signals is generated using a pair of acoustically matched piezoelectric transducers. The resulting acoustic radiation force is used to trap micron scale particles at a series of arbitrary positions (determined by the relative phase) and then move them in a controlled manner. This method is demonstrated experimentally and 5 μm polystyrene particles are trapped and moved in one dimension through 140 μm.


The association of antibodies against human T cell lymphotropic virus type I (HTLV-I) pX gene mutant products with HTLV-I-associated myelopathy/tropical spastic paraparesis.
Antibodies specific for the products of the human T cell lymphotropic virus type I (HTLV-I) pX frame-shift mutants were studied by ELISA. The serum IgG antibodies to the synthetic peptide corresponding to one nucleotide insertion at position 7784 were significantly more common in patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients than in HTLV-I carriers who had neither HAM/TSP nor adult T cell leukemia (39% vs. 5%). The seropositivities to the other synthetic peptides, which corresponded to the one nucleotide deletion at position 7475 and the internal deletion of nt 7754-7819 and nt 7853-7936, were rare. A genetic study confirmed the presence of the responsible mutation of the pX gene in peripheral blood mononuclear cells and central nervous system tissue from HTLV-I-infected subjects with and without HAM/TSP. These results suggest that HTLV-I pX frame-shift mutants are expressed in vivo in HTLV-I carriers; they also induce antibodies. especially in those with HAM/TSP.


99Tcm-pyrophosphate myocardial scintigraphy: the role of volume-rendered three-dimensional imaging in the diagnosis of acute myocardial infarction.
The aim of this study was to evaluate the role of volume-rendered three-dimensional imaging in the diagnosis of acute myocardial infarction (AMI) using 99Tcm-pyrophosphate (99Tcm-PYP) scintigraphy in a diagnostically difficult group of patients. In total, 117 patients were studied using planar, single photon emission tomography (SPET) and 3-D volume-rendered imaging performed 3 h after receiving 555 MBq (15 mCi) of 99Tcm-PYP intravenously. 555MBq (15 mCi) of 99Tcm-PYP intravenously. Two teams of physicians reported in a blinded and random fashion on each planar, SPET and 3-D rotating image study. Individual reports were compared with reports that used all three imaging modalities in combination. Observer reproducibility was between 85 and 90% and inter-observer team agreement was between 87 and 91%. A score based on clinical history, electrocardiography, serum cardiac enzyme levels and cardiac risk factors was validated and used as a de facto 'gold standard' for AMI for 75 of the subjects for whom all these details were available. The sensitivity, specificity and overall accuracy of combined planar, SPET and 3-D rotating image modalities were all 84%. Analysis of each modality in isolation showed SPET imaging to have the highest sensitivity (74%) and specificity (89%). In combination with SPET and planar imaging, 3-D rotation image presentation increases diagnostic sensitivity without appreciably altering overall diagnostic accuracy. 99Tcm-PYP myocardial SPET imaging shows good utility in the diagnosis of AMI in diagnostically difficult patients.


The surgical treatment for atrial fibrillation: ablation technology and surgical approaches.
The Cox maze procedure developed originally in 1987 by Dr James Cox has evolved from a "cut and sew" surgical procedure, where the maze was applied using multiple surgical cuts, to an extensive use of surgical ablation technology where ablation lesions are placed with alternative energy sources (radiofrequency, cryothermy, microwave, and high-frequency ultrasound). Furthermore, the procedure has changed from a median sternotomy approach only to one that can be performed minimally invasively and robotically. The purpose of this paper is to review the current available technology for the ablation of atrial fibrillation as well as the different procedural approaches for the surgical ablation of atrial fibrillation.


The Risk of Herpes Zoster in Women with Polycystic Ovary Syndrome: A Retrospective Population-Based Study.
Background: The association between polycystic ovary syndrome (PCOS) and the risk of herpes zoster (HZ) remains unclear. This study investigated the risk of HZ in women with PCOS. Methods: This study used data from the Longitudinal Generation Tracking Database (LGTD 2005) which contains the information of 2 million randomly selected from National Health Insurance beneficiaries. Patients who received a diagnosis of PCOS between 2000 and 2017 were included in the PCOS cohort. Patients who were not diagnosed as having PCOS were randomly selected from the LGTD 2005 and included in the control cohort. Patients who were aged <20 years and had a history of HZ before the index date were excluded. Patients who were in both the cohorts were matched at a ratio of 1:1 through propensity score matching based on age, comorbidities, and medication. The primary outcome was the diagnosis of HZ. Results: A total of 20,142 patients were included in each case and control cohorts. The incidence rates of HZ in the PCOS and control cohorts were 3.92 and 3.17 per 1000 person-years, respectively. The PCOS cohort had a significantly higher risk of HZ than did the control cohort (adjusted hazard ratios [aHR] = 1.26). Among the patients aged 30−39 years, those with PCOS had a significantly higher risk of HZ than did those without PCOS (aHR = 1.31). Among the patients without any comorbidities, those with PCOS had a significantly higher risk of HZ (aHR = 1.26) than did those without PCOS. Conclusion: PCOS is associated with the risk of HZ, especially in young women. The risk of HZ should be addressed while treating patients with PCOS. An HZ vaccine is recommended for these patients.


Visual and Colorimetric High-Throughput Analysis of Chiral Carboxylic Acids Based on Enantioselective Charge Shielding of Gold Nanoparticles.
Because chiral carboxylic acids (CCAs) are a class of important biological molecules and common functional moieties found in pharmaceutical molecules, the chiral analysis of CCAs has received much attention. Herein, we developed a simple, rapid, and cost-effective method for visual and colorimetric high-throughput analysis of CCAs using chiral di-imine structure-modified gold nanoparticles (C-AuNPs) as the probe. The C-AuNPs are positively charged in the presence of zinc ion, and they can be enantioselectively shielded by the negatively charged CCA enantiomers. Therefore, upon the addition of different concentrations and enantiomeric excess (ee) of CCAs, the C-AuNP-based sensor shows the different levels of aggregation along with the visual changes in solution color, which can achieve simultaneous analysis of the concentration and ee of CCAs. The chiral recognition mechanism based on C-AuNPs was investigated by the determination of binding constants ( K) and molecular simulation methods. Our approach is expected to have the wide-ranging applications in the developing region for enantio-sensing of various chiral drugs and biomolecules.


PFOS induced precocious hatching of Oryzias melastigma--from molecular level to individual level.
Perfluorooctane sulfonate (PFOS) showed a risk of causing adverse effects including hatching of animals. However, there are no systematical studies about the effects of PFOS on fish embryo hatching. In this study, a precocious hatching was detected in Oryzias melastigma embryos upon PFOS exposure. The average hatching time was shortened and the hatching rate increased after PFOS exposure. The subsequent survival rate decreased significantly in the larvae hatching from the PFOS-treated embryos compared to the control. The influence occurred in a PFOS concentration-dependent manner. To further elucidate the inner molecular change, full length cDNAs of hatching enzymes HCE and LCE were first cloned in O. melastigma by degenerate RT-PCR and RACE. PFOS elicited a transcriptional response of both HCE and LCE. The expressions of both genes were significantly up-regulated earlier in the PFOS-treated group than in the control group. The activity of hatching enzyme also significantly increased upon exposure. In all, our results showed that exposure to PFOS could induce the hatching enzyme both at transcriptional and enzymatic activity level and further lead to the precocious hatching of O. melastigma embryos, which induced the decrease of the subsequent larvae survival.


Respiratory Muscle Strengths and Their Association with Lean Mass and Handgrip Strengths in Older Institutionalized Individuals.
The study of reduced respiratory muscle strengths in relation to the loss of muscular function associated with ageing is of great interest in the study of sarcopenia in older institutionalized individuals. The present study assesses the association between respiratory muscle parameters and skeletal mass content and strength, and analyzes associations with blood cell counts and biochemical parameters related to protein, lipid, glucose and ion profiles. A multicenter cross-sectional study was performed among patients institutionalized in nursing homes. The respiratory muscle function was evaluated by peak expiratory flow, maximal respiratory pressures and spirometry parameters, and skeletal mass function and lean mass content with handgrip strength, walking speed and bioimpedance, respectively. The prevalence of reduced respiratory muscle strength in the sample ranged from 37.9% to 80.7%. Peak expiratory flow significantly (p < 0.05) correlated to handgrip strength and gait speed, as well as maximal inspiratory pressure (p < 0.01). Maximal expiratory pressure significantly (p < 0.01) correlated to handgrip strength. No correlation was obtained with muscle mass in any of parameters related to reduced respiratory muscle strength. The most significant associations within the blood biochemical parameters were observed for some protein and lipid biomarkers e.g., glutamate-oxaloacetate transaminase (GOT), urea, triglycerides and cholesterol. Respiratory function muscle parameters, peak expiratory flow and maximal respiratory pressures were correlated with reduced strength and functional impairment but not with lean mass content. We identified for the first time a relationship between peak expiratory flow (PEF) values and GOT and urea concentrations in blood which deserves future investigations in order to manage these parameters as a possible biomarkers of reduced respiratory muscle strength.


In the Wnt of Paneth Cells: Immune-Epithelial Crosstalk in Small Intestinal Crohn's Disease.
Paneth cells, specialized secretory epithelial cells of the small intestine, play a pivotal role in host defense and regulation of microbiota by producing antimicrobial peptides especially-but not only-the human α-defensin 5 (HD5) and HD6. In small intestinal Crohn's disease (CD) which is an entity of inflammatory bowel diseases, the expression of HD5 and HD6 is specifically compromised leading to a disturbed barrier and change in the microbial community. Different genetically driven but also non-genetic defects associated with small intestinal CD affect different lines of antimicrobial Paneth cell functions. In this review, we focus on the mechanisms and the crosstalk of Paneth cells and bone marrow-derived cells and highlight recent studies about the role of the Wnt signaling pathway in this connection of ileal CD. In summary, different lines of investigations led by us but also now numerous other groups support and reconfirm the proposed classification of this disease entity as Paneth's disease.


Genetic diversity of wild rodents and detection of Coxiella burnetii, the causative agent of Q fever, in Saudi Arabia.
Throughout history, wildlife has been regarded as a major source of infectious diseases. Rodentia, the most speciose order of mammals, whose members are recognised hosts of more than 60 zoonotic diseases, represent a potential threat to human health. Recently, epidemiological data from Saudi Arabia indicated an actual growth in the number of emerging and/or re-emerging cases of several zoonoses. However, there is a lack of studies focusing on the molecular taxonomy of rodents and the pathogens they may harbour in this region. In this study, the first molecular characterisation of six rodent taxa in this region is provided, based on partial Cyt B and 16S genes. The data confirm the spread of rodent-associated C. burnetii strains in Jazan, southwestern Saudi Arabia. The PCR targeting IS111, the multi-copy transposase gene, revealed 17.5% (36/205) positive samples, whereas the second nested PCR, targeting the single-copy Com1 gene, revealed 16.6% (34/205) positive samples. Phylogenetic and network analyses indicated the presence of four haplotypes of C. burnetii within the studied localities. One major haplotype (H-2) was observed in all rodent species and from 18 localities. The infection rates of C. burnetii among studied species, localities and habitats were not significantly different (>0.05). Our results facilitate the assessment of the health risk associated with rodents and the development of strategies to control the increasing impacts of Q fever.


Relative Validity and Reproducibility of a Semi-Quantitative Food Frequency Questionnaire for Determining Nutrient Intake in Older Adults in New Zealand: The REACH Study.
Dietary intake is an important predictor of health and disease outcomes. This cross-sectional study evaluated the relative validity and reproducibility of a semi-quantitative food frequency questionnaire (FFQ) for assessing energy and nutrient intake in older adults. Dietary data were collected 2018-2019 in Auckland, New Zealand from a convenience sample of community-dwelling adults (65-74 years, n = 294, 37% male) using a 109-item self-administered FFQ at baseline (FFQ1) and four weeks later to assess reproducibility. FFQ1 was compared to a four-day food record to determine relative validity. Agreement between dietary assessment tools was assessed for both raw and energy-adjusted nutrient intakes using paired t-tests, correlation coefficients, weighted kappa statistic, Bland-Altman plots, and linear regression analysis. Energy adjustments moderately improved the relative validity and reproducibility for most nutrients. For energy and energy-adjusted nutrient intakes, the mean correlation coefficients were 0.38 (validity) and 0.65 (reproducibility); the mean weighted kappa statistics were 0.27 (validity) and 0.51 (reproducibility). A significant slope of bias was present in 54% (validity) and 25% (reproducibility) of Bland-Altman plots. The Researching Eating, Activity, and Cognitive Health (REACH) FFQ has acceptable relative validity and good reproducibility for ranking nutrient intakes in older New Zealand adults, but is less suitable for assessing absolute nutrient intakes.


Medical and Endoscopic Management of Crohn Disease.
In this review, through a series of questions and answers, we explore the current approach to classifying patients with Crohn disease into low-risk (mild-moderate) and high-risk (moderate-severe) categories with the recommended treatment approaches per guidelines from the International Organization for the Study of Inflammatory Bowel Diseases, American Gastroenterological Association, the American College of Gastroenterology, and the European Crohn's and Colitis Organization detailed here. The development pipeline of potential therapies is also summarized. We also review key information from magnetic resonance enterography and pelvis imaging studies that the abdominal radiologist can communicate to a multidisciplinary treatment team that includes gastroenterologists and colorectal surgeons, with a goal of achieving optimal patient outcomes. Lastly, endoscopic and radiological treatment targets in a treat-to-target approach in Crohn disease are explored.


Pathogenicity of avian nephritis virus in chicks previously infected with infectious bursal disease virus.
Pathogenicity of avian nephritis virus (ANV) was studied in 7-day-old chicks previously infected with infectious bursal disease virus (IBDV) at 1 day of age. Three IBDV+ANV infected chicks were found dead with no apparent clinical signs within 10 days of inoculation with ANV and they had marked urate deposits throughout the body. All of the surviving IBDV+ANV infected chicks had reduced body weight gain, unlike the ANV-only infected, IBDV-only infected and non-infected control chicks. In a chronological study, all of the ANV-infected chicks revealed interstitial nephritis accompanied by tubular cell degeneration and lymphoid cell infiltration. Avian nephritis virus antigen was detected with equal sensitivity by fluorescent antibody and immunoperoxidase techniques and was widely distributed in the degenerated epithelial cells. The concentration of serum uric acid in IBDV+ANV infected chicks was higher than that in ANV-only infected chicks. The antibody against ANV in ANV-only infected chicks was first detected 8 dpi and its titre increased gradually. In contrast, the antibody in the IBDV+ANV infected chicks was very low and was detected in only three out of seven chicks 16 dpi; the titre was 1:4 in one chick and 1:8 in the other 2 chicks. Coincident with serological results, the number of lgG- and IgM-containing cells in the kidneys and spleen were less in IBDV + ANV-infected chicks than in ANV-only infected chicks. These finding suggested that IBDV infection in chicks might influence the immunological response and susceptibility to subsequent ANV infection.


Biobehavioral influences on energy intake and adult weight gain.
U.S. adults are now gaining more weight and becoming obese at an earlier age than in previous years. The specific causes of adult weight gain are unknown, but may be attributed to a combination of factors leading to positive energy balance. U.S. food supply data indicate that Americans have had a gradual increase in energy intake since 1970, and that per capita energy intake was 1.42 MJ/d (340 kcal/d) higher in 1994 than that in 1984. In contrast, self-reported physical activity remained constant between 1990 and 1998. Taken together, these data indicate that the increasing trend in U.S. adult weight gain is primarily attributable to overconsumption of energy. Epidemiological and experimental studies in animals and humans provide strong evidence that biobehavioral factors such as dietary variety, liquid (vs. solid) energy, portion size, palatability (taste), snacking patterns, restaurant and other away-from-home food, and dietary restraint and disinhibition influence hunger, satiety and/or voluntary energy intake. When these eating behaviors are consistently experienced either separately or in combination over the long term, they are likely to facilitate overeating. We provide a brief overview of the evidence to date for the role of these biobehavioral factors in contributing to excess energy intake and increases in body weight over time.


A novel tumor spheroid model identifies selective enhancement of radiation by an inhibitor of oxidative phosphorylation.
There is a need for preclinical models that can enable identification of novel radiosensitizing drugs in clinically relevant high-throughput experiments. We used a new high-throughput compatible total cell kill spheroid assay to study the interaction between drugs and radiation in order to identify compounds with radiosensitizing activity. Experimental drugs were compared to known radiosensitizers and cytotoxic drugs clinically used in combination with radiotherapy. VLX600, a novel iron-chelating inhibitor of oxidative phosphorylation, potentiated the effect of radiation in tumor spheroids in a synergistic manner. This effect was specific to spheroids and not observed in monolayer cell cultures. In conclusion, the total cell kill spheroid assay is a feasible high-throughput method in the search for novel radiosensitizers. VLX600 shows encouraging characteristics for development as a novel radiosensitizer.


Treatment decisions about lumbar herniated disk in a shared decision-making program.
An explicit process of collaborative (shared) decision making involving the patient and physician has been recommended for discretionary surgical procedures in which small-area analysis demonstrates high variation not attributable to differences in the patient population in the area. One such example is laminectomy for lumbar herniated disk (HD). An observational study was undertaken to evaluate the impact of an HD videodisk program on patient satisfaction, decision making, and treatment preferences. Enrollment occurred in the outpatient offices of surgeons treating Kaiser Permanente (Colorado Region) patients with HD who had indications for surgery. Enrollment took place from May 1993 to December 1995, and follow-up surveys of patients were completed by January 1997. A 6.0% decrease in the undecided group and a 1.3% decrease in the group preferring nonsurgical treatment drove a shift of patients toward laminectomy, from 26.7% to 35.8% (Wilcoxon signed rank test = 349.5, p = .017). Postviewing preference (74.0%) was a better aggregate predictor of the ultimate treatment than previewing preference (70.0%) for laminectomy. Viewing the videodisk increased the preference for laminectomy. However, limitations in the data prevented us from determining whether this change in preference was actually reflected in patients' ultimate decisions. The fact that the strongest predictor of choosing surgery was the patient's valuation of his or her condition supports shared decision making, with its emphasis on patient's values. Participation in other videodisk programs has been low; perhaps physicians should ask patients to view these videodisks before their visits.


Principles of Public Reason in the UNFCCC: Rethinking the Equity Framework.
Since 2011, the focus of international negotiations under the UNFCCC has been on producing a new climate agreement to be adopted in 2015. This phase of negotiations is known as the Durban Platform for Enhanced Action. The goal has been to update the global effort on climate for long-term cooperation. In this period, various changes have been contemplated on the design of the architecture of the global climate effort. Whereas previously, the negotiation process consisted of setting mandated targets exclusively for developed countries, the current setting requests of each country to pledge its contribution to the climate effort in the form of Intended Nationally Determined Contributions (INDCs). The shift away from establishing negotiated targets for rich countries alone towards a universal system of participation through intended contributions raised persistent questions on how exactly the new agreement can ensure equitable terms. How to conceptualize equity within the 2015 climate agreement, and beyond, is the focus of this paper. The paper advances a framework on equity, which moves away from substantive moral conceptions of burden allocation toward refining principles of public reason specially designed for the negotiation process under the UNFCCC. The paper outlines the framework's main features and discusses how it can serve a facilitating role for multilateral discussion on equity on a long-term basis capable of adapting to changing circumstances.


Synthesis of the p10 single-stranded nucleic acid binding protein from murine leukemia virus.
The p10 murine leukemia virus (MuLV) protein is a basic single-stranded nucleic acid binding protein encoded by the extreme 3' region of the gag gene of MuLV type C. It contains the Cys-X2-Cys-X4-His-X4-Cys sequence shared by all retroviral gag polyproteins. A similar sequence is found in the gene 32 single-stranded DNA binding protein of bacteriophage T4 and is believed to be the zinc binding region of the protein. Solid phase synthesis of p10 was carried out based on the known primary structure of the native protein, with the exception that the acetamidomethyl (Acm) derivative of cysteine was incorporated at all three cysteine positions. The structure of the synthetic p10 was confirmed by direct amino-acid sequencing, as well as by amino acid analysis and FAB mass spectrometry of endoproteinase Lys-C peptides derived from p10. A Chou and Fasman analysis of the primary sequence predicts that p10 contains 9% beta strand and/or sheet and 36% alpha helix. Circular dichroism experiments carried out on the Acm derivatized peptide gave somewhat different results, in that they suggest that p10 contains approximately 70% random coil, less than 30% beta strand and/or sheet and less than 10% alpha helix. With a Ka of greater than 10(8) M-1 for single-stranded RNA, the synthetic peptide binds as tightly as the p10 protein does when isolated directly from infected HTG-2 cells. The Acm groups can be removed from the synthetic p10 peptide by the use of mercuric acetate, followed by treatment with dithiothreitol to sequester the mercuric ion.(ABSTRACT TRUNCATED AT 250 WORDS)


The effect of nasal continuous positive airway pressure on the symptoms of Gulf War illness.
We performed a pilot study to determine whether nasal continuous positive airway pressure (CPAP) alleviates the symptoms of veterans with Gulf War illness (GWI) and sleep disordered breathing (SDB). Eighteen male veterans with GWI and SDB recruited by advertisement, participated in a randomized, single-masked, sham-controlled treatment trial. Participants received 3 weeks of treatment during sleep with either therapeutic nasal CPAP or sham nasal CPAP. Using validated questionnaires, pain, fatigue, cognitive function, sleep disturbance, and general health were assessed by self-report before and after treatment. One of the participants assigned to therapeutic CPAP was excluded from the trial before starting treatment, leaving 17 participants. Compared to the nine sham nasal CPAP recipients, the eight participants receiving therapeutic nasal CPAP experienced improvements in pain (34%; p = 0.0008), fatigue (38%; p = 0.0002), cognitive function (33%; p = 0.004), sleep quality (41%; p = 0.0003), physical health (34%; p = 0.0003), and mental health (16%; p = 0.03). Our findings in this pilot study suggest that nasal CPAP may greatly improve symptoms in veterans with GWI and SDB.


Positive regulation of the pts operon of Escherichia coli: genetic evidence for a signal transduction mechanism.
The pts operon of Escherichia coli is composed of the genes ptsH, ptsI, and crr, which code for three proteins of the phosphoenolpyruvate-dependent phosphotransferase system (PTS): the HPr, enzyme I (EI), and EIIIGlc proteins, respectively. These three genes are organized in a complex operon in which the major part of expression of the distal gene, crr, is initiated from a promoter region within ptsI. Expression from the promoter region of the ptsH and ptsI genes has been studied in vivo by using gene fusions with lacZ. Transcription from this promoter region is under the positive control of catabolite activator protein (CAP)-cyclic AMP (cAMP) and is also enhanced during growth in the presence of glucose (a PTS substrate). This report describes a genetic characterization of the mechanism by which growth on glucose causes transcriptional stimulation of the pts operon. This regulation is dependent on transport through the glucose-specific permease of the PTS, EIIGlc. Our results strongly suggest that transcriptional regulation of the pts operon is the consequence of an increase in the level of unphosphorylated EIIGlc which is produced during glucose transport. Furthermore, overproduction of EIIGlc in the absence of transport was found to stimulate expression of the pts operon. We also observed that CAP-cAMP could cause stimulation independently of the EIIGlc and that glucose could activate in the absence of cAMP in a strain overproducing EIIGlc. Our results indicate that glucose acts like an environmental signal through a mechanism of signal transduction. A sequence similarity between the C terminus of EIIGlc and the consensus of transmitter modules of the sensor proteins defined by E. C. Kofoid and J. S. Parkinson (Proc. Natl. Acad. Sci. USA 85:4981-4985, 1988) suggests that EIIGlc might have properties in common with the sensors of the two-component systems.


Asthma remission: does it exist?
Subjects believed to have grown out of asthma often develop symptoms again later in life. Ongoing airway inflammation may determine the risk of relapse, although the mechanisms involved are still misunderstood. Additionally, patients with asthma during childhood may develop irreversible airflow obstruction ( airway remodeling) as a result of chronic airway inflammation. Recently, airway inflammation and remodeling could be demonstrated in bronchial biopsy specimens from young adults who considered themselves grown out of asthma. It is also shown that evidence of airway inflammation and remodeling can be obtained noninvasively, thereby providing the opportunity to monitor disease activity. If chronic airway inflammation and/or remodeling are consistent findings in asymptomatic subjects with a history of atopic asthma, the question arises whether natural history can be positively altered with prolonged antiinflammatory therapy. Benefits of long-term prognosis are, however, not yet shown. Since epidemiologic work has demonstrated that a certain percentage of subjects with apparently outgrown atopic asthma remains asymptomatic without needing therapy for the rest of their lives, it can be argued that "asthma remission does exist." The question is whether this percentage can be increased with prolonged antiinflammatory therapy and regular control.


Medicare program; inpatient hospital deductible for 1990--HCFA. Notice.
This notice announces that the inpatient hospital deductible for calendar year 1990 under Medicare's hospital insurance program (Part A) is +592. The Medicare statute specifies the formula to be used to determine this amount.


Pramipexole in treatment-resistant depression: a 16-week naturalistic study.
To assess the antidepressant efficacy and tolerability of adjunctive pramipexole, a D2-D3 dopamine agonist, in patients with drug-resistant depression. The study sample consisted of in-patients with major depressive episode, according to the DSM-IV, and drug resistance. Pramipexole was added to antidepressant treatment with TCA or SSRI, at increasing doses from 0.375 to 1.0 mg/day. Two independent response criteria were adopted: a > 50% reduction of the Montgomery-Asberg Depressive Rating Scale (MADRS) total score and a score of I or 2 on the Clinical Global Impression scale (CGI-1) at endpoint. Side-effects were assessed by the Dosage Record Treatment Emergent Symptom Scale (DOTES). Thirty-seven patients were enrolled. Of these. 16 had unipolar depression and 21 had bipolar depression. Six patients dropped out in the first week. Of the 31 patients included in the analyses. 19 completed the 16-week follow-up. Mean maximal dose of pramipexole was 0.95 mg/day. Mean scores on MADRS decreased from 33.3 +/- 8.4 at baseline to 13.9 +/- 11.5 at endpoint (p < 0.001) and the CGI-S decreased from 4.6 +/- 0.8 at baseline to 2.8 +/- 1.3 at endpoint (p < 0.001). At endpoint, 67.7% (21/31) of patients were responders on MADRS and 74.2% on CGI-I. Of the 37 patients enrolled, 10 discontinued pramipexole because of adverse events. These preliminary data suggest that pramipexole adjunction to antidepressant treatment may be effective and well tolerated in patients with resistant major depression.


Isolation and characterization of the human inter-alpha-trypsin inhibitor family heavy chain-related protein (IHRP) gene (ITIHL1).
Inter-alpha-trypsin inhibitor (ITI) family heavy chain-related protein (IHRP) is a novel human glycoprotein that shows significant homology in amino acid sequence to proteins of the ITI family heavy chains from human plasma. Three overlapping clones that encode the human inter-alpha-trypsin inhibitor family heavy chain-related protein (IHRP) gene (ITIHL1) were isolated and characterized. The IHRP gene spans 15 kb and is composed of 24 exons from 27 to 207 bp in size with consensus splice sites. The gene codes for the precursor of IHRP, which is similar to inter-alpha-trypsin inhibitor (ITI) family heavy chains. Two major transcription initiation sites were identified in the 5'-flanking region. They contain putative promoter elements, but no typical TATA box. Some exons of this gene showed significant similarities to those of the ITI-H1 gene in nucleotide length and in intron phasing. The tissue-specific transcription of this gene may be due to the presence of binding sites for the hepatocyte nuclear factors LF-A1, HNF-5, NF-IL6, and C/EBP. This gene was found to be localized very close to another unknown gene related to EST (GenBank accession #: R54643, R50663, R50563, H27139, and R54913).


Proteinase inhibitors from the molting fluid of the pharate adult tobacco hornworm, Manduca sexta.
The molting fluid of pharate adult Manduca sexta was found to contain at least two types of proteinase inhibitor activities. One inhibited the native cuticle degrading trypsin-like proteinase, MFP1, while the other was found to be highly specific for subtilisin-like enzymes. The developmental profiles of both these inhibitor activities were investigated. MFP-1 inhibitor activity was found to be present in the molting fluid of all stages of pre-ecdysial development, except stage 7, which possessed the highest levels of MFP-1 activity. The inhibitor was estimated to have a relative molecular mass of 14.5 k and was found to be heat stable. A role in regulation of cuticle degradation is suggested. Subtilisin inhibitor activity was found in molting fluid from all eight stages of pre-ecdysial development, although there was some variation observed between the stages when inhibitor activities were visualized using PAGE zymograms. A subtilisin inhibitor was purified using Sep-Pak cartridges and Reverse Phase HPLC. The inhibitor was found to be of low relative molecular mass (11 k), heat stable, and highly specific for fungal enzymes such as PR1 from the entomopathogen Metarhizium anisopliae. Therefore, a role in insect defense is suggested.


Classification of morphea (localized scleroderma)
To classify and describe morphea (localized scleroderma). A review of morphea and its subtypes is presented. The current classification of morphea is incomplete and confusing. As knowledge of the spectrum of disease continues to evolve, the controversy and confusing nature of its multiple subtypes present a challenge for the physician who encounters a patient with this condition. Thus, we propose that morphea be classified into the following five groups: plaque, generalized, bullous, linear, and deep. This classification, based on clinical morphologic findings, will simplify the diagnostic and therapeutic approach. Morphea represents a wide variety of clinical entities that seen to be on the opposite end of the scleroderma spectrum from systemic sclerosis. The cutaneous lesions eventually evolve from a sclerotic stage to a nonindurated stage, and residual hypopigmentation or hyperpigmentation follows. The histologic pattern in patients with morphea is similar to that in patients with progressive systemic sclerosis. Although treatment is nonstandardized, hydroxychloroquine sulfate may be beneficial.


Return to Being Black, Living in the Red: a race gap in wealth that goes beyond social origins.
In the United States, racial disparities in wealth are vast, yet their causes are only partially understood. In Being Black, Living in the Red, Conley (1999) argued that the sociodemographic traits of young blacks and their parents, particularly parental wealth, wholly explain their wealth disadvantage. Using data from the 1980-2009 waves of the Panel Study of Income Dynamics, I show that this conclusion hinges on the specific sample considered and the treatment of debtors in the sample. I further document that prior research has paid insufficient attention to the possibility of variation in the association between wealth and race at different points of the net worth distribution. Among wealth holders, blacks remain significantly disadvantaged in assets compared with otherwise similar whites. Among debtors, however, young whites hold more debt than otherwise similar blacks. The results suggest that, among young adults, debt may reflect increased access to credit, not simply the absence of assets. The asset disadvantage for black net wealth holders also indicates that research and policy attention should not be focused only on young blacks "living in the red."


The B7-CD28 superfamily.
The B7-1/B7-2-CD28/CTLA-4 pathway is crucial in regulating T-cell activation and tolerance. New B7 and CD28 molecules have recently been discovered and new pathways have been delineated that seem to be important for regulating the responses of previously activated T cells. Several B7 homologues are expressed on cells other than professional antigen-presenting cells, indicating new mechanisms for regulating T-cell responses in peripheral tissues. Some B7 homologues have unknown receptors, indicating that other immunoregulatory pathways remain to be described. Here, we summarize our current understanding of the new members of the B7 and CD28 families, and discuss their therapeutic potential.


[Imaging benign tumors of the pleura].
Five percent of pleural tumors are benign. Solitary fibrous tumors are the most frequent. We recall the clinical and pathological features and present the radiographic, computed tomographic and magenetic resonance imaging results obtained for the main types of benign tumors of the pleura.


Acknowledging and overcoming barriers to entry into radiation science for women.
Radiation science is a unique field that brings together various disciplines to understand nature, develop new technologies, and cure diseases. Our field is a prime example of advancement through a diverse pool of competencies. Similarly, studies show that the power of diversity requires proportionate representation of sex and gender, minorities, or other groups. Nevertheless, women are still underrepresented in the radiation sciences, although disparities and underlying mechanisms were first described decades ago. This review summarizes barriers to entry and retention and suggests strategies for overcoming disparities in our field. We also highlight a concerted effort by young professionals to promote the underrepresented and underserved within the radiation science community. The radiation science community should avoid losing diverse perspectives among its ranks due to sex bias or gender disparity among others. Through targeted efforts, we can cultivate change and harness the talent of researchers, practitioners, and other professionals for the benefit of scientific progress, health-care improvement, and societal advancement overall.


Effect of infusion of salmon calcitonin on the secretion of somatostatin and gastrin in man.
In vitro and animal studies have pointed out complex interrelations between gastrointestinal hormones and calcitonin. To analyse the acute effects of calcitonin in more detail, patients undergoing surgery were infused intravenously with synthetic salmon calcitonin, a potent analog of the human hormone. Samples were taken after 0, 30 and 60 minutes from the hepatic, portal and a peripheral vein. Somatostatin and gastrin were determined by radioimmunoassay. The mean basal levels of somatostatin in peripheral and hepatic venous plasma (14.2 and 15.6 pg/ml) were significantly lower than in portal plasma (45.6 pg/ml), indicating effective removal by the liver. After infusion of calcitonin there was a general rise in somatostatin levels and an increase in the gradient between hepatic and portal blood. Basal gastrin levels were highest in the portal vein when compared intraindividually. The differences disappeared after calcitonin infusion with a concomitant systemic reduction of gastrin levels. Thus, calcitonin is able to stimulate the secretion of somatostatin from the gastrointestinal tract and does reduce gastrin secretion, possibly via the stimulation of somatostatin secretion.


Treatment of acute ischemic stroke: recent progress.
Intravenous thrombolysis with tissue plasminogen activator is currently the most effective treatment of acute ischemic stroke if administerd within 3 hours after symptom onset. Intraarterial thrombolysis by prourokinase is the another choise if the middle cerebral artery is occluded and within less than 6 hours after onset. Although heparin especially a moderate dose is not proved to be effective, a randomized, placebo-controlled trial to determine the safety and efficacy of argatroban (a selective thrombin inhibitor) in patients with acute ischemic stroke was started in USA. Aspirin provides some benefit to patients with acute stroke. However, its effect is not fully satisfactory. Although reports of numerous trials for neuroprotective drugs have been disappointing, edaravone (free radical scavenger) was approved for the treatment of acute ischemic stroke in Japan. In the future, thrombolytic and neuroprotective drugs will be used in combination.


Monolithic barrier-all-around high electron mobility transistor with planar GaAs nanowire channel.
High-quality growth of planar GaAs nanowires (NWs) with widths as small as 35 nm is realized by comprehensively mapping the parameter space of group III flow, V/III ratio, and temperature as the size of the NWs scales down. Using a growth mode modulation scheme for the NW and thin film barrier layers, monolithically integrated AlGaAs barrier-all-around planar GaAs NW high electron mobility transistors (NW-HEMTs) are achieved. The peak extrinsic transconductance, drive current, and effective electron velocity are 550 μS/μm, 435 μA/μm, and ~2.9 × 10(7) cm/s, respectively, at 2 V supply voltage with a gate length of 120 nm. The excellent DC performance demonstrated here shows the potential of this bottom-up planar NW technology for low-power high-speed very-large-scale-integration (VLSI) circuits.


[Importance of dosimetric factors predicting radiation toxicity in lung cancer treatment].
To evaluate prognostic importance of dosimetric parameters (V20, V30 and V40) in the incidence of lung radiation toxicity caused by external-beam radiation therapy in patients with lung cancer. A total of 82 patients with lung cancer were analyzed prospectively. They were treated in the Oncology Institute of Vilnius University from 2002 to 2005. Three-dimensional conformal radiotherapy was administered to all patients; radiation dose was > or =50 Gy, delivered in daily fractions of 2 Gy. All patients received concurrent chemotherapy and part of them - surgery. All patients were evaluated before radiation therapy and after 3-, 6-, and 12-month follow-up. V20, V30, and V40 were calculated from dose-volume histograms using the Eclipse(TM) radiotherapy treatment planing system. Based on radiological findings and clinical symptoms radiation-induced lung injury (radiation pneumonitis and radiation fibrosis) was diagnosed. Nearly half of patients (48%) developed grade < or =2 pulmonary toxicity according to the Subjective, Objective, Management and Analytic/Late Effects on Normal Tissues (SOMA/LENT) scale. The percentage volume of normal lung tissue receiving >20 Gy dose was 38%, >30 Gy--25%, and >40 Gy--18%. In patients free of radiation toxicity V20 was 30%, V30--22%, and V40--18%, and in patients with radiation-induced pulmonary toxicity V20 was 48%, V30--30%, and V40--18%. Dosimetric parameters V20, V30, and V40 are significant predictive factors for radiation-induced pulmonary toxicity. At this time planned V20 and V30 are too high and they should be minimized in order to reduce radiation-induced pulmonary toxicity.


Correlation between catalytic activity and monomer-dimer equilibrium of bacterial alanine racemases.
From the reaction mechanism and crystal structure analysis, a bacterial alanine racemase is believed to work as a homodimer with a substrate, l-alanine or d-alanine. We analysed oligomerization states of seven alanine racemases, biosynthetic and catabolic, from Escherichia coli, Salmonella typhimurium, Pseudomonas aeruginosa, P. putida and P. fluorescens, with three different methods, gel filtration chromatography, native PAGE and analytical ultracentrifugation. All alanine racemases were proved to be in a dynamic equilibrium between monomeric and dimeric form with every methods used in this study. In both biosynthetic and catabolic alanine racemases, association constants for dimerization were high for the enzymes with high V(max) values. The enzymes with low V(max) values gave the low association constants. We proposed that alanine racemases are classified into two types; the enzymes with low and high-equilibrium association constants for dimerization.


Current Advances of Tubulin Inhibitors in Nanoparticle Drug Delivery and Vascular Disruption/Angiogenesis.
Extensive research over the last decade has resulted in a number of highly potent tubulin polymerization inhibitors acting either as microtubule stabilizing agents (MSAs) or microtubule destabilizing agents (MDAs). These inhibitors have potent cytotoxicity against a broad spectrum of human tumor cell lines. In addition to cytotoxicity, a number of these tubulin inhibitors have exhibited abilities to inhibit formation of new blood vessels as well as disrupt existing blood vessels. Tubulin inhibitors as a vascular disrupting agents (VDAs), mainly from the MDA family, induce rapid tumor vessel occlusion and massive tumor necrosis. Thus, tubulin inhibitors have become increasingly popular in the field of tumor vasculature. However, their pharmaceutical application is halted by a number of limitations including poor solubility and toxicity. Thus, recently, there has been considerable interests in the nanoparticle drug delivery of tubulin inhibitors to circumvent those limitations. This article reviews recent advances in nanoparticle based drug delivery for tubulin inhibitors as well as their tumor vasculature disruption properties.


[3 cases of acute postoperative pancreatitis].
After a brief review of the literature the authors present three cases of acute postoperative pancreatitis in patient operated for different reasons with lethal outcome. In one patient the complication developed after duodeno-hemipancreatectomy and is the only patient with such complication (2 per cent) of 50 patients in whom radical operation was performed for cancer of the pancreas over the period Jan. 1983-May 1990. The current aspects of the etiology, treatment and above all of the prophylaxis of acute postoperative pancreatitis, which is a very serious postoperative complication with very high case fatality rate (up to 77 per cent, according to data in the literature) are discussed.


A modified mouse peripheral blood lymphocyte culture system for cytogenetic analysis.
A detailed methodology is presented for culturing mouse peripheral blood lymphocytes isolated on density gradients and stimulated to divide using either phytohemagglutinin, concanavalin A, or lipopolysaccharide. The techniques described yield more than sufficient numbers of mitotic cells for analyzing sister chromatid exchange, chromosome aberrations, and micronuclei following in vitro or in vivo exposure to chemicals or radiation.


Adult coeliac disease in Ireland: a case series.
The clinical spectrum of adult coeliac disease (ACD) is varied with limited Irish data. The aim of this study was to analyse the presenting symptoms, associated conditions and complications in a consecutive series of patients with ACD. Data were obtained from database on patients with ACD between 1988 and 2004. One hundred and six patients (69F:37M, mean age: 46, range: 23-95 years) were included. The modes of presentation were diarrhoea in 44 patients (45%), weight loss in 41 (42%), anaemia in 37 (38%), abdominal pain in 15 (15%), fatigue in 8 (8%), hypocalcaemia in 4 (4%) and steatorrhoea in 4 (4%). Associated conditions included thyroid disorders in 7 patients (7%), bipolar affective disorder in 4 (4%), major depression in 3 (3%), rheumatoid disease in 3 (3%), inflammatory bowel disease in 4 (4%) and type I diabetes mellitus in 2 (2%). Malignancy emerged as a major complication in 15 patients (15%) The presenting features of ACD are diverse and associated with high risk of malignancy.


CT perfusion and noncontrast CT in acute ischemic stroke diagnosing--is there influence on early thrombolytic therapy outcome?
The objective of this study was to compare noncontrast computed tomography (NCCT) and computed tomography perfusion (CTP) in early diagnosis of acute ischemic stroke and to define influence of these diagnostic procedures on early outcome of thrombolytic therapy (TLTH). The study included 45 patients, 35 patients submitted to NCCT and CTP and 10 patients who underwent only NCCT, before CTP was introduced. Based on the National Institute of Health Stroke Scale (NIHSS) score we compared early outcome of patients who received TLTH after NCCT only (group 1) with the early outcome of patients who received TLTH following NCCT and CTP (group 2). Statistically significant difference was found in acute stroke diagnosing between CTP and NCCT (p = 0.002). There were no statistically significant differences in TLTH early outcome between group 1 and group 2. In conclusion, CTP should be done regulary in patients presenting with acute ischemic stroke symptoms. More research needs to be done in defining exact influence of CTP implementation on the TLTH outcome.


Antifungal and Aflatoxin-Reducing Activity of β-Glucan Isolated from Pichia norvegensis Grown on Tofu Wastewater.
Yeast can be isolated from tofu wastewater and the cell wall in the form of β-glucan can act as a natural decontaminant agent. This study aimed to isolate and characterize native yeast from tofu wastewater, which can be extracted to obtain β-glucan and then identify the yeast and its β-glucan activity regarding antifungal ability against Aspergillus flavus and aflatoxin-reducing activity towards aflatoxin B1 (AFB1) and B2 (AFB2). Tofu wastewater native yeast was molecularly identified, and the growth observed based on optical density for 96 h and the pH also measured. β-glucan was extracted from native yeast cell walls with the acid-base method and then the inhibition activity towards A. flavus was tested using the well diffusion method and microscopic observation. AFB1 and AFB2 reduction were identified using HPLC LC-MS/MS. The results showed that the native yeast isolated was Pichia norvegensis with a β-glucan yield of 6.59%. Pichia norvegensis and its β-glucan showed an inhibition zone against Aspergillus flavus of 11.33 ± 4.93 and 7.33 ± 3.51 mm, respectively. Total aflatoxin-reducing activity was also shown by Pichia norvegensis of 26.85 ± 2.87%, and β-glucan of 27.30 ± 1.49%, while AFB1- and AFB2-reducing activity by Pichia norvegensis was 36.97 ± 3.07% and 27.13 ± 1.69%, and β-glucan was 27.13 ± 1.69% and 32.59 ± 4.20%, respectively.


Clonally related penicillin-nonsusceptible Streptococcus pneumoniae serotype 14 from cases of meningitis in Salvador, Brazil.
Active hospital-based surveillance in the city of Salvador, Brazil, from December 1995 through October 1998, identified 221 patients with confirmed pneumococcal meningitis. Of these 221 patients, 29 (13%) had isolates with intermediate-level resistance to penicillin. Infection with these penicillin-nonsusceptible isolates was significantly associated with age of <2 years (P<.0019), previous antibiotic use (P<.0006), and coresistance to trimethoprim-sulfamethoxazole (P<.0000). Serotype 14 was the most prevalent serotype (55.2%) of penicillin-nonsusceptible isolates. Strain typing by repetitive element BOX polymerase chain reaction (PCR) analysis showed that penicillin-nonsusceptible serotype 14 isolates had closely related BOX PCR patterns, whereas penicillin-susceptible serotype 14 isolates each had distinct, unrelated patterns. Penicillin-nonsusceptible serotype 14 isolates from Salvador and other Brazilian cities had similar BOX PCR patterns. These observations indicate that in Brazil a large proportion of cases of penicillin-nonsusceptible pneumococcal meningitis appear to be caused by a closely related group of serotype 14 strains that may have disseminated to widely separate geographic areas.


Discovery and Facile Synthesis of a New Silicon Based Family as Efficient Hydrogen Evolution Reaction Catalysts: A Computational and Experimental Investigation of Metal Monosilicides.
A new family of transition-metal monosilicides (MSi, M = Ti, Mn, Fe, Ru, Ni, Pd, Co, and Rh) electrocatalysts with superior electrocatalytic performance of hydrogen evolution is reported, based on the computational and experimental results. It is proposed that these MSi can be synthesized within several minutes by adopting the arc-melting method. The previously reported RuSi is not only fabricated more readily but eventually explored 8 MSi that can be good hydrogen evolution reaction catalysts. Silicides then can be another promising electrocatalysts family as carbides, wherein carbon has the same electronic configuration as silicon. All explored silicides electrodes exhibited low overpotentials (34-54 mV at 10 mA cm-2 ) with Tafel slopes from 23.6 to 32.3 mV dec-1 , which are comparable to that of the commercial 20 wt% Pt/C (37 mV, 26.1 mV dec-1 ). First-principles calculations demonstrated that the superior performance can be attributed to the high catalytic reactivity per site that can even function at high hydrogen coverages (≈100%) on multiple low surface energy facets. The work sheds light on a new class of electrocatalysts for hydrogen evolution, with earth-abundant and inexpensive silicon-based compounds.


Finite-size effects in the conductivity of cluster assembled nanostructures.
Atomic clusters have been deposited between lithographically defined contacts with nanometer scale separations. The design of the contacts is based on an appropriate application of percolation theory to conduction in cluster deposited devices and allows finite-size effects to be clearly observed. It is demonstrated, both by experiment and by simulation, that for small contact separations the percolation threshold is shifted to extremely low surface coverages. The selected rectangular contact geometry ensures that wirelike structures are formed close to the percolation threshold.


Intensity dependent time-resolution and dynamic range of Photochron picosecond streak-cameras.
The dynamic range of operation of Photochron I and Photochron II picosecond streak cameras is shown to depend upon the time-resolution employed. For events approximately 2 ps a useful dynamic range of 30 is obtainable, and this increases to a value of 180 for 30-ps events. No accumulative saturation effects occur at a time resolution as short as 2 ps.


Modifications involved by acetylacetone in properties of sol-gel derived Y(3)Al(5)O(12):Tb(3+)- II: optical features.
Tb(3+)-doped Y(3)Al(5)O(12) powders have been synthesized from alkoxide precursors using, or not using, acetylacetone as a chemical modifier. The terbium oxidation state and local environment of amorphous and crystallized powders have been comparatively investigated by means of X-ray absorption near-edge structures (XANES) and extended X-ray absorption fine structure (EXAFS) while laser-induced luminescence was used to study their optical properties. Excitation and emission spectra have been recorded and a relative luminescence yield has been assessed upon 277 nm excitation. Whatever the sample, the terbium oxidation state remains +III and, for a similar heating treatment until 900 degrees C, its local environment appears to be better organized in powders modified by acetylacetone. Structural parameters obtained during XAS study are consistent with the YAG structure in which Tb atoms are in solid solution with Y ones. Besides, Tb(3+) characteristic green luminescence has been recorded for all samples, even those amorphous. It has been evidenced that the use of acetylacetone leads to more efficient luminescent materials for calcination temperatures ranging from 400 degrees C to 900 degrees C upon 277 nm excitation. Discrepancies between optical properties will be discussed with regards to the terbium local environment and expected luminescence features.


[Indoor air pollution with polycyclic aromatic hydrocarbons caused by polycyclic aromatic hydrocarbon containing parquet floor adhesives. Report of current status for evaluating and dealing with this "new chronic pollution" of indoor air].
In 1997 so far unknown indoor contaminations were detected in a flat of former American Forces living quarters in Frankfurt/Main, Germany. Household dust samples were found to be contaminated with polycyclic aromatic hydrocarbons (PAH), respectively with benzo(a)pyrene (BaP), due to the use of a coal tar pitch parquet glue that had been standard building practice in Germany up to the 'sixties. To assess the amount of exposure, the local Health Services department organised analyses of PAH metabolites in the urine of children below 6 years of age considered to be at risk for oral exposure to BaP in household dust while playing on the floor. In addition the local Health Services informed all ministeries concerned of the problem. During the following months several meetings on this topic were held by experts in the respective spheres and recommendations for redeveloping indoor sites were outlined. In almost 3,000 analyses of samples of household dust and parquet glue and about 1,200 urine analyses for PAH-metabolites in Frankfurt/Main no correlation was seen between the BaP levels in parquet glue and the BaP levels in household dust samples, as well as with interual exposure. Recommendations for further action were made in view of the importance of the composition of parquet flooring for possible indoor contamination.


Bullous Amyloidosis Masquerading as Pseudoporphyria.
Amyloidosis is not a singular disease but describes a group of diseases that result from abnormalities in protein folding and metabolism, leading to β-sheet polymers and amyloid fibrils. Cutaneous involvement is common and may occur as a primary disorder or secondary to systemic disease. Bullous skin changes, however, are rare occurrences in cutaneous amyloidosis. Bullous amyloidosis presents with characteristic histopathologic, immunohistochemical, and immunofluorescence patterns, all of which allow for careful distinction from other similar diseases. Importantly, bullous amyloidosis should prompt consideration of an underlying diagnosis of a lymphoproliferative disorder. We present the case of a woman who was diagnosed with bullous amyloidosis due to multiple myeloma after an extensive workup initially suggested other bullous diseases. We highlight the importance of recognizing this rare entity to prevent delay in diagnosis and management of its underlying cause.


[Heel pain and calcaneal spurs].
The authors of this paper have reviewed 137 X-ray films of the involved feet and followed up 30 patients all of them suffering from heel pain treated in the authors' hospital during 1980-1985, in order to find out the relationship between the length, shape and the direction of the spurs with the heel pain. We have found: (1) There are no clear relationship between heel pain and the length, shape and the direction of the calcaneal spur. (2) The plantar soft tissue of the painful foot was thickened, indicating the heel pain was due to inflammation in the plantar soft tissue. (3) Heel pain is related to the patient's age and sex. (4) The spurs still exist and grow even bigger after the syndrome disappears.