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Exercise-induced serum enzyme elevations confounding the evaluation of investigational drug toxicity. Report of two cases in a vaccine trial. Two subjects developed marked elevations in creatine kinase and other serum enzymes associated with mild myalgia during a randomized, double-blind, controlled Phase 1 clinical trial of an investigational live, attenuated vaccine against West Nile virus (ChimeriVax-WN02). One subject had received ChimeriVax-WN02 while the other subject was enrolled in an active control group and received licensed yellow fever 17D vaccine (YF-VAX). Subsequently, the clinical trial was interrupted, and an investigation was begun to evaluate the enzyme abnormalities. As daily serum samples were collected for determination of quantitative viremia, it was possible to define the enzyme elevations with precision and to relate these elevations to physical activity of the subjects, symptoms, and virological and serological measurements. Evaluation of both subjects clearly showed that skeletal muscle injury, and not cardiac or hepatic dysfunction, was responsible for the biochemical abnormalities. This investigation also implicated strenuous exercise as the cause of the apparent muscle injury rather than the study vaccines. As a result of this experience, subjects engaged in future early-stage trials of these live, attenuated viral vaccines will be advised not to engage in contact sports or new or enhanced exercise regimens for which they are not trained or conditioned. The inclusion of placebo control arm (in lieu of or addition to an active vaccine control) will also be useful in differentiating causally related serum enzyme elevations.

Genotoxicity of phenacetin in the kidney and liver of Sprague-Dawley gpt delta transgenic rats in 26-week and 52-week repeated-dose studies. Transgenic rat mutation assays can be used to assess genotoxic properties of chemicals in target organs for carcinogenicity. Mutations in transgenes are genetically neutral and accumulate during a treatment period; thus, assays are suitable for assessing the genotoxic risk of chemicals using a repeated-dose treatment paradigm. However, only a limited number of such studies have been conducted. To examine the utility of transgenic rat assays in repeated-dose studies, we fed male and female Sprague-Dawley gpt delta rats with a 0.5% phenacetin-containing diet for 26 and 52 weeks. A long-term feeding of phenacetin is known to induce renal cancer in rats. Phenacetin administration for 52 weeks in males significantly increased gpt (point mutations) mutant frequency (MF) in the kidney, the target organ of carcinogenesis. In the liver, the nontarget organ of carcinogenesis, gpt MFs were significantly elevated in phenacetin treatment groups of both genders during 26- and 52-week treatments. Furthermore, sensitive to P2 interference (Spi(-)deletions) MF increased in the liver of both genders following 52-week treatment. MFs were higher after treatment for 52 weeks than after treatment for 26 weeks. Frequencies of phenacetin-induced mutations were higher in the liver than in the kidney, suggesting that the intensity of genotoxicity does not necessarily correlate with the induction of tumor formation. Results from gpt delta rat assays of repeated-dose treatments are extremely useful to elucidate the relationship between gene mutations and carcinogenesis in the target organ induced by cancer-causing agents.

Decomposition pathway of KAlH4 altered by the addition of Al2S3. Altering the decomposition pathway of potassium alanate, KAlH4, with aluminium sulfide, Al2S3, presents a new opportunity to release all of the hydrogen, increase the volumetric hydrogen capacity and avoid complications associated with the formation of KH and molten K. Decomposition of 6KAlH4-Al2S3 during heating under dynamic vacuum began at 185 °C, 65 °C lower than for pure KAlH4, and released 71% of the theoretical hydrogen content below 300 °C via several unknown compounds. The major hydrogen release event, centred at 276 °C, was associated with two new compounds indexed with monoclinic (a = 10.505, b = 7.492, c = 11.772 Å, β = 122.88°) and hexagonal (a = 10.079, c = 7.429 Å) unit cells, respectively. Unlike the 6NaAlH4-Al2S3 system, the 6KAlH4-Al2S3 system did not have M3AlH6 (M = alkali metal) as one of the intermediate decomposition products nor were the final products M2S and Al observed. Decomposition performed under hydrogen pressure initially followed a similar reaction pathway to that observed during heating under vacuum but resulted in partial melting of the sample between 300 and 350 °C. The measured enthalpy of hydrogen absorption (ΔHabs) was in the range -44.5 to -51.1 kJ mol-1 H2, which is favourable for moderate temperature hydrogen applications. Although, the hydrogen capacity decreases during consecutive H2 release and uptake cycles, the presence of excess amounts of aluminium allow for further optimisation of hydrogen storage properties.

Label-free visual biosensor based on cascade amplification for the detection of Salmonella. Salmonella is a widely distributed, extremely harmful bacteria, the presence of which requires confirmation via an on-site visual biosensor. In this study, we constructed a label-free, cascade amplification visualization biosensor for the sensitive and rapid detection of Salmonella enterica subsp. enterica serovar typhimurium based on the RDTG principle (recombinase polymerase amplification (RPA), duplex-specific enzyme (DSN) cleavage, terminal deoxynucleotidyl transferase (TdT) extension and G-quadruplexes output). Following DNA extraction of Salmonella spp., the first step in the construction involved the recognition and amplification of nucleic acids, carried out by RPA, to achieve the first signal amplification within 10 min. This RPA product was then specifically cleaved by DSN to produce a large number of small double-stranded DNA (dsDNA) products with 3'-OH within 15 min to achieve the second signal amplification. Thereafter, TdT was employed to empower these small 3'-OH dsDNA products to extend and produce a large number of long G-rich single-stranded DNAs (ssDNAs) within 20 min, thus realizing the third signal increase. These long G-rich ssDNA products displayed a color change that could be directly observed through the naked eye by adding H2O2/3,3',5,5'-tetramethylbenzidine (TMB). The RDTG biosensor for the detection of Salmonella spp. has several advantages, including a low limit of 6 cfu/mL. It is an isothermal-free instrument, simple to operate, with a rapid detection time of less than 1.5 h. Furthermore, it can be visually characterized and quantified by a microplate reader to detect Salmonella spp., in food and environmental samples, and it has broad application prospects.

Viral brachial neuritis in emergency medicine. Brachial plexus neuritis is a rare neurologic disease that may be overlooked in emergency medicine because other conditions are much more common. We report a case of brachial plexus neuropathy due to cytomegalovirus infection. The diagnosis was based on history, clinical findings, laboratory tests, and electromyography. Early diagnosis and adequate treatment is important to avoid unnecessary investigation, prevent complications (especially adhesive capsulitis of the shoulder), and reassure the patient.

Differential modulation by interferon gamma of the sensitivity of human melanoma cells to cytolytic T cell clones that recognize differentiation or progression antigens. Human melanoma is a highly immunogenic tumor capable of inducing a specific immune response. A number of melanoma-associated antigens have been characterized during the past several years and can be classified into two groups: differentiation antigens-present also in normal melanocytes-and tumor-specific antigens, which, with the exception of testis, are present only in tumor cells. In a previous publication [Kirkin A. F., Petersen T. R., Olsen A. C., Li L., thor Straten P., Zeuthen J. (1995) Cancer Immunol Immunother 41:71] we have described the production of clones of cytotoxic T lymphocytes (CTL) against the highly immunogenic human melanoma cell line FM3. Using these clones we have defined four previously unknown melanoma-associated antigens, which could be subdivided into differentiation and progression antigens. In the experiments reported in this paper, we have further compared CTL clones from different groups and shown that the sensitivity of melanoma cells to CTL that recognize differentiation or progression antigens is differentially modulated during tumor progression as well as by the lymphokines interferon gamma (IFN gamma) and interleukin-10 (IL-10). The interaction of CTL clones recognizing progression antigens was strongly increased after treatment of melanoma cells with IFN gamma, while the recognition by CTL clones specific for differentiation antigens either was unchanged or significantly decreased. IL-10 treatment of melanoma cells induced up-regulation with respect to recognition by CTL clones specific for differentiation antigens without affecting the recognition of melanoma cells by CTL clones specific for progression antigens. Using cellular systems at different stages of tumor progression, we demonstrated that the progressed state of melanoma cells is associated with increased sensitivity to recognition by CTL clones detecting progression antigens, and with decreased sensitivity to CTL clones recognizing differentiation antigens. Mimicking tumor progression, treatment with IFN-gamma induced apparent down-regulation of differentiation antigens. A hypothesis is suggested in which IFN-gamma plays different roles in the immune response against poorly immunogenic and highly immunogenic melanoma cells, increasing the progression of poorly immunogenic tumor cells or promoting a strong immune response and regression of highly immunogenic melanoma cells.

Characterization of leucine transport by toadfish liver in vivo. Kinetic analysis of L-leucine uptake by toadfish liver at 20 degrees C in vivo has been carried out after pulse injection of L-[14C]leucine into the hepatic portal vein. D-[3H]mannitol, which is taken up slowly by toadfish liver, is used as a marker for extracellular space and space accessible by simple diffusion. At normal plasma leucine concentration (0.1 mM), leucine uptake occurs rapidly (t1/2 = 0.25 min), representing a flux of 0.6 mumol/min for the liver as a whole. Analysis of the distribution of radioactive leucine among intracellular and extracellular free pools and protein-bound form at times of 30 s to 5 min after injection is consistent with operation of a concentrative or uphill transport system accounting for 40% of uptake at normal plasma concentration. Saturation of uptake occurs at increasing leucine loads; calculation of intracellular pool dilution from protein synthesis data indicates that 20-30% of liver intracellular space is occupied by incoming leucine during the first 2 min after portal injection. Maximal flux (V max) is 4.1 mumol/min per 7-g liver as a whole with Km = 0.6 mM. Competitive inhibition of leucine uptake is afforded by isoleucine and phenylalanine with lesser effects by aspartic acid, cysteine, methionine, threonine, tyrosine, and valine. No effect is observed with alanine, glycine, histidine, lysine, and proline.

Proteomic analysis of S-nitrosylated proteins in Arabidopsis thaliana undergoing hypersensitive response. Nitric oxide (NO) has a fundamental role in the plant hypersensitive disease resistance response (HR), and S-nitrosylation is emerging as an important mechanism for the transduction of its bioactivity. A key step toward elucidating the mechanisms by which NO functions during the HR is the identification of the proteins that are subjected to this PTM. By using a proteomic approach involving 2-DE and MS we characterized, for the first time, changes in S-nitrosylated proteins in Arabidopsis thaliana undergoing HR. The 16 S-nitrosylated proteins identified are mostly enzymes serving intermediary metabolism, signaling and antioxidant defense. The study of the effects of S-nitrosylation on the activity of the identified proteins and its role during the execution of the disease resistance response will help to understand S-nitrosylation function and significance in plants.

Low-Dose Versus High-Dose Tranexamic Acid Reduces the Risk of Nonischemic Seizures After Cardiac Surgery With Cardiopulmonary Bypass. The incidence of postoperative nonischemic seizures associated with the use of tranexamic acid (TXA) and the possibility of prevention with a low-dose regimen of TXA were evaluated. Retrospective study. Tertiary care university hospital. A total of 12,195 patients who underwent cardiac surgical procedures under cardiopulmonary bypass (CPB) were evaluated. The files of every clinical seizure case diagnosed in the surgical intensive care unit between April 2006 and April 2014 were reviewed. Patients who experienced a postoperative seizure underwent a cerebral computed tomography scan to exclude an ischemic lesion. Dosage and type of antifibrinolytic used and surgery characteristics were retrieved from perfusion files. Low-dose TXA was defined as 1,000-mg bolus, 400-mg/h infusion, and 500 mg in CPB priming. High-dose TXA was defined as 30-mg/kg bolus, 15 mg/kg/h, and 2 mg/kg in CPB priming. No seizure was observed in the 886 patients who did not receive antifibrinolytics. A total of 98 clinical seizures (0.8%) were recorded in the intensive care unit, and ischemic cause was excluded in the majority of them after computed tomography scan results were reviewed (91 patients [93%]). Low-dose TXA was associated with fewer seizures than was high-dose TXA (46 of 7,452 cases [0.70%] v 34 of 2,190 cases [1.55%], respectively; p < 0.0001). Open-chamber cardiac surgery also was linked to a higher incidence of seizures compared with revascularization (80 of 6,662 [1.20%] and 11 of 5,533 [0.20%], respectively; p < 0.0001). Lower doses of TXA were associated with a lower incidence of nonischemic seizures compared with higher doses of the drug.

[Urodynamics of the upper urinary tract in urolithiasis patients with chronic pyelonephritis]. Urodynamics was studied in patients with chronic pyelonephritis with a various level of upper urinary tract (UUT) obstruction. 90% patients with concrements of the low ureter had high intrapelvic pressure (IPP)--21.8 +/- 0.8/25.2 +/- 0.8 cm of water column (basal/peristaltic) and enhanced UUT contractility. IPP was elevated in 50% patients with proximal UUT obstruction (11.8 +/- 1.3/15.5 +/- 1.5 cm of water column) and it rose noticeably (by 110-184%) in changing body position (orthostatic test) but changed little in the respiratory test. High IPP persisted despite functioning nephrostomic drainages in 84-86% patients exposed to extracorporeal and/or contact lithotripsy at the average level 16.2 +/- 0.8/19.7 +/- 0.6 cm of water column. Different mechanisms may be involved in formation of high IPP in patients with chronic pyelonephritis and varying level of UUT obstruction. In view of damaging influence of high IPP on renal function the physician should control this index during the treatment and take additional measures to prevent elevation of IPP.

Polymer coatings that display specific biological signals while preventing nonspecific interactions. Control over cell-material surface interactions is the key to many new and improved biomedical devices. It can only be achieved if interactions that are mediated by nonspecifically adsorbed serum proteins are minimized and if cells instead respond to specific ligand molecules presented on the surface. Here, we present a simple yet effective surface modification method that allows for the covalent coupling and presentation of specific biological signals on coatings which have significantly reduced nonspecific biointerfacial interactions. To achieve this we synthesized bottle brush type copolymers consisting of poly(ethylene glycol) methyl ether methacrylate and (meth)acrylates providing activated NHS ester groups as well as different spacer lengths between the NHS groups and the polymer backbone. Copolymers containing different molar ratios of these monomers were grafted to amine functionalized polystyrene cell culture substrates, followed by the covalent immobilization of the cyclic peptides cRGDfK and cRADfK using residual NHS groups. Polymers were characterized by GPC and NMR and surface modification steps were analyzed using XPS. The cellular response was evaluated using HeLa cell attachment experiments. The results showed strong correlations between the effectiveness of the control over biointerfacial interactions and the polymer architecture. They also demonstrate that optimized fully synthetic copolymer coatings, which can be applied to a wide range of substrate materials, provide excellent control over biointerfacial interactions.

Three-body wear of light-activated composite veneering materials. The in vitro wear of two types of composite resin veneering materials was determined by use of a three-body wear testing device. The wear of a microfilled high-filler content composite resin (Dentacolor) was less than that of a hybrid low-filler content one (Visio-Gem). The worn surface of Dentacolor material was smoother than that of Visio-Gem material. The wear-testing results and scanning electron micrographs demonstrated that the findings obtained by this wear-testing device correlated well with clinical findings.

Diagnosis of bowel and mesenteric injuries in blunt abdominal trauma: a prospective study. Currently, nonoperative management is the procedure of choice for solid organ injury in patients with a blunt abdominal trauma. Missed blunt bowel and mesenteric injuries (BBMIs) are possible because diagnosis is difficult. The aim of our study was to test a new algorithm for BBMI diagnosis using abdominal ultrasonography (AUS), computed tomography (CT), and diagnostic peritoneal lavage (DPL). We reviewed cases of blunt abdominal injuries over a 10-year period, then we designed an algorithm that was prospectively tested in hemodynamically stable patients over a 2-year period. An abnormal AUS led to helical CT. When the CT showed more than 2 findings suggestive of BBMI, laparotomy was performed. In case of 1 or 2 abnormal CT findings, we performed a DPL and calculated the ratio of white blood cells (WBCs) to red blood cells (RBCs) (WBC/RBC ratio) in the lavage fluid and divided this by the WBC/RBC ratio in peripheral blood. A ratio of 1 or higher was considered positive for BBMI, and a laparotomy was immediately performed. Patients with a ratio of less than 1 were managed nonoperatively. In the retrospective study, 26 (1%) of 2126 patients admitted to our trauma center for blunt trauma had a BBMI, including 15 (58%) diagnosed after a median delay of 24 hours. In the prospective study, 531 patients were admitted for blunt trauma with multiple injuries, including 131 with abdominal trauma. Computed tomography was performed in 40 patients. There were 2 criteria or more of BBMI in 1 patient, 0 criteria in 27 patients (with an uneventful follow-up), and 1 or 2 criteria in 12 patients who had DPL with a median ratio of 0.82 (ranges, 0.03-9). Five patients had a ratio of 1 or higher. They underwent immediate laparotomy. In all 5 cases, BBMI was found. The 7 patients who had a ratio of less than 1 were observed in ICU and treated for extra-abdominal injuries. No BBMI injury was missed in these patients. The accuracy of the algorithm was 100% (95% confidence interval, 0.99-1.00). The proposed algorithm (based on AUS, CT, and DPL) had a high accuracy to diagnose BBMI while requiring the performance of DPL in only a few (2%) patients.

Electrical conduction through DNA molecule. Several disorder parameters, inside the DNA molecule, lead to localization of charge carriers inside potential wells in the lowest unoccupied and highest occupied molecular orbits (LUMO and HOMO) which affects drastically the electrical conduction through the molecule, and demonstrates that the band carriers play an essential role in the conduction mechanism. So, a model is presented to shed light on the role of electrons of the LUMO in the electrical conduction through the DNA molecule. DC-, AC-conductivity and dielectric permittivity experimental data are well fitted with the presented model giving evidence that the free carriers in the LUMO and HOMO are responsible to make the DNA molecule conductor, insulator or semiconductor. The obtained results show that the localized charge carriers in the DNA molecule are characterized by four different types of relaxation phenomena which are thermally activated by corresponding four activation energies at 0.56 eV, 0.33 eV, 0.24 eV, and 0.05 eV respectively. Moreover, the calculations after the model, at room temperature, show that the time of the relaxation times of the current carriers are in the order of 5 × 10(-2)s, 1.74 × 10(-4)s, 5 × 10(-7)s, and 1.6 × 10(-10)s, respectively.

Legislating collaborative self-regulation in Canada: A comparative policy analysis. To encourage interprofessional collaboration and to improve the regulation of healthcare providers, Ontario and Nova Scotia, Canada, have each adopted legislation calling for collaboration among the regulators of their self-regulating health professions. Ontario's legislation is "top down": it came from government and stresses the obligation of regulators to collaborate. Nova Scotia's legislation is "bottom up": it was proposed and developed by regulators and emphasizes voluntary regulatory collaboration. This article considers the theoretical strengths and weaknesses of both models. It argues that Nova Scotia's approach may be stronger because of its relative consistency with core strengths of self-regulation and interprofessionalism and its grounding in soft law and a governance approach to collaborative self-regulation and to healthcare policy more broadly.

LncRNA-TP53TG1 Participated in the Stress Response Under Glucose Deprivation in Glioma. Gliomas are the most common brain tumors of the center nervous system. And long non-coding RNAs (lncRNAs) are non-protein coding transcripts, which have been considered as one type of gene expression regulator for cancer development. In this study, we investigated the role of lncRNA-TP53TG1 in response to glucose deprivation in human gliomas. The expression levels of TP53TG1 in glioma tissues and cells were analyzed by qRT-PCR. In addition, the influence of TP53TG1 on glucose metabolism related genes at the mRNA level during both high and low glucose treatment was detected by qRT-PCR. MTT, clonogenicity assays, and flow cytometry were performed to detect the cell proliferation and cell apoptosis. Furthermore, the migration of glioma cells was examined by Transwell assays. The expression of TP53TG1 was significantly higher in human glioma tissues or cell lines compared with normal brain tissue or NHA. Moreover, TP53TG1 and some tumor glucose metabolism related genes, such as GRP78, LDHA, and IDH1 were up-regulated significantly in U87 and LN18 cells under glucose deprivation. In addition, knockdown of TP53TG1 decreased cell proliferation and migration and down-regulated GRP78 and IDH1 expression levels and up-regulated PKM2 levels in U87 cells under glucose deprivation. However, over-expression of TP53TG1 showed the opposite tendency. Moreover, the effects of TP53TG1 were more remarkable in low glucose than that in high glucose. Our data showed that TP53TG1 under glucose deprivation may promote cell proliferation and migration by influencing the expression of glucose metabolism related genes in glioma. J. Cell. Biochem. 118: 4897-4904, 2017. © 2017 Wiley Periodicals, Inc.

Classification of morphologically similar algae and cyanobacteria using Mueller matrix imaging and convolutional neural networks. We present the Mueller matrix imaging system to classify morphologically similar algae based on convolutional neural networks (CNNs). The algae and cyanobacteria data set contains 10,463 Mueller matrices from eight species of algae and one species of cyanobacteria, belonging to four phyla, the shapes of which are mostly randomly oriented spheres, ovals, wheels, or rods. The CNN serves as an automatic machine with learning ability to help in extracting features from the Mueller matrix, and trains a classifier to achieve a 97% classification accuracy. We compare the performance in two ways. One way is to compare the performance of five CNNs that differ in the number of convolution layers as well as the classical principle component analysis (PCA) plus the support vector machine (SVM) method; the other way is to quantify the differences of scores between full Mueller matrix and the first matrix element m11, which does not contain polarization information under the same conditions. As the results show, deeper CNNs perform better, the best of which outperforms the conventional PCA plus SVM method by 19.66% in accuracy, and using the full Mueller matrix earns 6.56% increase of accuracy than using m11. It demonstrates that the coupling of Mueller matrix imaging and CNN may be a promising and efficient solution for the automatic classification of morphologically similar algae.

Interaction between estrogen receptor alpha, ionizing radiation and (anti-) estrogens in breast cancer cells. Estrogen receptor alpha (ERalpha) plays a major role in breast cancer development. It acts as ligand-inducible transcription factor which determines growth, survival and differentiation of breast cancer cells. The aim of this study is to evaluate the potential interference between radiotherapy and estrogen receptor responsiveness. Materials and methods. The effect of ionizing radiation was assessed on the estrogen receptor alpha status, growth (proliferation and apoptosis) and sensitivity of MCF-7 breast cancer cells to estrogenic (17beta-estradiol (E2)), selective estrogen receptor modulator (SERM) and anti-estrogenic compounds. Results. We have observed a ligand-independent decrease in ERalpha expression after radiation, resulting from a specific reduction in mRNA level and protein synthesis. This ERalpha disappearance occurred 72 h post-irradiation at 8 Gy and decreased the transcriptional activity in ERalpha of these cells. On the other hand, E2 impedes the growth inhibitory effects (essentially on proliferation) of ionizing radiation in MCF-7 cells, which potentially decreases radiosensitivity of these cells. This effect was totally blocked by SERM and anti-estrogenic treatments. Moreover, this growth effect of concurrent anti-estrogenic drugs and ionizing radiation appeared to be strongly synergistic. This study may increase general comprehension of ERalpha modulation by radiotherapy and improve adjuvant therapeutic approaches based on co-administration of radiation and endocrine therapy.

[The "SYNAPSY" project: where psychiatrists and neuroscientists meet]. The National Center of Competence in Research project "SYNAPSY" aims at identifying certain mechanisms of psychiatric and cognitive disorders, in order to improve the understanding and the genesis of such pathologies, and to promote the development of better diagnostic tools and of new therapeutic approaches. It provides an excellent opportunity for clinical psychiatrists and neuroscientists to develop a synergic mode of collaboration. On the basis of questions stemming from clinical practice and in the frame of patients cohorts, various research projects in neuroscience should lead to progresses that may have a considerable impact on clinical practice.

[Clinical analysis of 30 patients with perineal endometriosis]. To investigate the diagnosis and treatment of perineal endometriosis. The clinical date of 30 patients with perineal endometriosis, aged 32.3 (23 approximately 44), who were admitted 1983 - 2006, operated on, and followed up for 0.5 approximately 13 years, were analyzed. The incidence of perineal endometriosis was 0.32% among the total endometriosis cases. Five of these 30 patients (16.7%) suffered from perineal endometriosis combined with pelvic endometriosis. The latent period was 4 months to 13 years. There was no significant difference in onset of age. All patients had cyclical and painful lesions. The level of CA125 was normal. All patients were cured after complete surgical excision. Diagnosis of perineal endometriosis can be made based on the patients' history and clinical manifestations. Surgical excision is the first choice of treatment. The recurrent rate of the cases without anal sphincter involvement is lower than that with anal sphincter invasion since the complete incision can be made. It is important to evaluate pre-operatively if the anal sphincter is involved.

Electroanalytical determination of acetaminophen using nano-TiO(2)/polymer coated electrode in the presence of dopamine. We report a new method for selective determination of acetaminophen (AP) in physiological condition. A new hybrid film modified electrode was fabricated using inorganic semiconducting nano-TiO(2) particles and redox active polymer. Redox polymer, poly(acid yellow 9) (PAY) was electrochemically deposited onto nano-TiO(2) coated glassy carbon (GC) electrode. Surface characterizations of modified electrode were investigated by using atomic force microscope and scanning electron microscope. The PAY/nano-TiO(2)/GC hybrid electrode shows stable redox response in the pH range 1-12 and exhibited excellent electrocatalytic activities towards AP in 0.1M phosphate buffer solution (pH 7.0). Consequently, a simple and sensitive electroanalytical method was developed for the determination of AP. The oxidation peak current was proportional to the concentration of acetaminophen from 1.2 x 10(-5) to 1.20 x 10(-4)M and the detection limit was found to be 2.0 x 10(-6)M (S/N=3). Possible interferences were tested and evaluated that it could be possible to selective detection of AP in the presences of dopamine, nicotinamide adenine dinucleotide (NADH), ascorbic acid and uric acid. The proposed method was used to detect acetaminophen in commercial drugs and the obtained results are satisfactory.

Increased plasma S-adenosyl-homocysteine levels induce the proliferation and migration of VSMCs through an oxidative stress-ERK1/2 pathway in apoE(-/-) mice. Although S-adenosyl-homocysteine (SAH) is considered to be a more sensitive predictor of cardiovascular disease than homocysteine, the underlying mechanisms of its effects remain unknown. We investigated the in vivo and in vitro effects of SAH on vascular smooth muscle cells (VSMCs) proliferation and migration related to the development of atherogenesis in apolipoprotein E-deficient (apoE(-/-)) mice. A total of 72 apoE(-/-) mice were randomly divided into six groups (n= 12 for each group). The control group was fed a conventional diet, the M group was fed a 1% methionine-supplemented diet, the A group was fed a diet that was supplemented with the SAH hydrolase (SAHH) inhibitor adenosine-2, 3-dialdehyde (ADA), the M+A group was fed a diet that was supplemented with methionine plus ADA, and two of the groups were intravenously injected with retrovirus that expressed either SAHH shRNA (SAHH(+/-)) or scrambled shRNA semi-weekly for 8 weeks. Compared with the controls, the mice in the A, M+A, and SAHH(+/-) groups had higher plasma SAH levels, larger atheromatous plaques, elevated VSMC proliferation, and higher aortic reactive oxygen species and malondialdehyde levels. In cultured VSMCs, 5 μM ADA or SAHH shRNA caused SAH accumulation, which resulted in increased cell proliferation, migration, oxidative stress, and extracellular-regulated kinase 1/2 (ERK1/2) activation. These effects were significantly attenuated by preincubation with superoxide dismutase (300 U/mL). Our results suggest that elevated SAH induces VSMC proliferation and migration through an oxidative stress-dependent activation of the ERK1/2 pathway to promote atherogenesis.

Effect of route of nutrition on recovery of hepatic organic anion clearance after fasting. Previous work documented a 40% depression of hepatic indocyanine green (ICG) clearance (ClICG) in pigs fasted to 20% weight loss, with return to normal within 12 days of food refeeding. ClICG in pigs is insensitive to changes in hepatic blood flow but very sensitive to changes in hepatic function (HF). Serial ClICG determinations were performed to quantify the effect of route of nutrient delivery on recovery of HF. Fourteen pigs were fasted to 20% weight loss (12.8 days average) with both gastrostomy and intravenous catheters placed in each animal midway through the fast. ClICG was measured before fast, after fast, and after 12 days refeeding through the enteral or parenteral route at 125 kcal/kg/day with isonitrogenous, isocaloric diets containing 9% fat. Urine and stool were analyzed for total nitrogen. No significant differences appeared between groups in nitrogen output during fasting (4.5 +/- 1.2 gm/kg enteral, 4.6 +/- 1.2 gm/kg parenteral), in nitrogen intake (800 +/- 19 mg/kg/day enteral, 810 +/- 10 mg/kg/day parenteral), or in before or after fast ClICG, but enteral feeding produced more positive nitrogen balance. ClICG improved significantly with enteral but not with parenteral feeding. Enteral feeding produces faster nitrogen accrual and reverses the depression of major pathways of bilirubin and organic anion excretion associated with malnutrition. Parenteral feeding failed to improve organic anion clearance despite weight gain.

Does immunosuppressive pharmacotherapy affect isoagglutinin titers? Preoperative reduction of isoagglutinins leads to successful ABO-incompatible (ABOi) renal transplantation. The strategy includes pretransplantation plasmapheresis, more potent immunosuppressive drugs, splenectomy, and anti-CD20 antibody. It has been reported that low isoagglutinin antibody titers posttransplant were observed among ABOi renal transplants with favorable outcome. The isoagglutinin titers may increase slightly when plasmapheresis is discontinued; however, it never returns to the pretreatment level under immunosuppressive therapy. This raises the question of what occurs to the isoagglutinin titer in ABO-compatible renal transplants under maintenance immunosuppressive pharmacotherapy. We analyzed 10 renal transplant recipients, including seven living and three cadaveric donors. Patients were treated with basiliximab (20 mg) intravenously on day 0 and day 4. Maintenance immunosuppressive therapy involved a calcineurin inhibitor, mycophenolate mofetil, and steroid. Anti-human globulin isoagglutinin titers were routinely examined 1 day before and day 0 and 1, 2, 3, 4, 8, 12, and 24 weeks posttransplant. No ALG or intravenous immunoglobulin or plasmapheresis treatment was provided in the follow-up period. Our preliminary data showed nearly no influence on isoagglutinin titer levels in 6-month follow-up under maintenance immunosuppressive therapy. In addition, no significant difference in isoagglutinin titer was observed between tacrolimus and cyclosporine groups. Maintenance immunosuppressive pharmacotherapy did not affect isoagglutinin titer levels in ABO-compatible kidney transplants. Further study is needed to investigate the mechanisms of persistent low-level isoagglutinin titers among successful ABOi renal transplantation patients.

Localization and enzymatic activity profiles of the proteases responsible for tachykinin-directed oocyte growth in the protochordate, Ciona intestinalis. We previously substantiated that Ci-TK, a tachykinin of the protochordate, Ciona intestinalis (Ci), triggered oocyte growth from the vitellogenic stage (stage II) to the post-vitellogenic stage (stage III) via up-regulation of the gene expression and enzymatic activity of the proteases: cathepsin D, carboxypeptidase B1, and chymotrypsin. In the present study, we have elucidated the localization, gene expression and activation profile of these proteases. In situ hybridization showed that the Ci-cathepsin D mRNA was present exclusively in test cells of the stage II oocytes, whereas the Ci-carboxypeptidase B1 and Ci-chymotrypsin mRNAs were detected in follicular cells of the stage II and stage III oocytes. Double-immunostaining demonstrated that the immunoreactivity of Ci-cathepsin D was largely colocalized with that of the receptor of Ci-TK, Ci-TK-R, in test cells of the stage II oocytes. Ci-cathepsin D gene expression was detected at 2h after treatment with Ci-TK, and elevated for up to 5h, and then slightly decreased. Gene expression of Ci-carboxypeptidase B1 and Ci-chymotrypsin was observed at 5h after treatment with Ci-TK, and then decreased. The enzymatic activities of Ci-cathepsin D, Ci-carboxypeptidase B1, and Ci-chymotrypsin showed similar alterations with 1-h lags. These gene expression and protease activity profiles verified that Ci-cathepsin D is initially activated, which is followed by the activation of Ci-carboxypeptidase B1 and Ci-chymotrypsin. Collectively, the present data suggest that Ci-TK directly induces Ci-cahtepsin D in test cells expressing Ci-TK receptor, leading to the secondary activation of Ci-chymotrypsin and Ci-carboxypeptidase B1 in the follicle in the tachykininergic oocyte growth pathway.

Do neurological disorders in childhood pose a risk for mental health in young adulthood? To assess whether juvenile-onset epilepsy or motor disability is complicated by an increased number of mental health disorders or experience of psychosomatic symptoms in young adulthood, we studied 81 subjects with epilepsy and 52 with motor disabilities at the age of 19 to 25 years and compared them with 211 controls. The main diagnostic tool, the Present State Examination, was administered to those attending the interviews in person who were of normal intelligence; there were 62, 38, and 123 subjects in the three categories, respectively. Compared with the controls, the subjects with epilepsy showed an equal prevalence of psychiatric disorders whereas those with motor disabilities had a significantly higher prevalence, particularly of depressive disorders. The reported prevalence of psychosomatic symptoms confirmed this main result. Psychological illness affected everyday life of two out of five subjects with motor disabilities, but only half of those in the other two groups. It is concluded that motor disability since childhood, but not epilepsy, could be a factor that increases susceptibility to psychiatric morbidity, especially depression, and causes a large number of psychosomatic symptoms. The results challenge staff of clinics working with such adolescents to find individual approaches in preventing the negative influence of psychological disorders on social life.

Involvement of phosphorylation of Tyr-31 and Tyr-118 of paxillin in MM1 cancer cell migration. We demonstrated previously that rat ascites hepatoma MM1 cells require both lysophosphatidic acid (LPA) and fibronectin (FN) for phagokinetic motility and transcellular migration and that these events are regulated through the RhoA-ROCK pathway. It remains to be elucidated, however, how the signals from both LPA and FN are integrated into cell migration. To examine this, total cellular lysates after stimulation with LPA or FN were subjected to time-course immunoblot analysis with anti-phosphotyrosine antibodies (Abs). Consequently, tyrosine-phosphorylation of paxillin was obviously persistent after stimulation with FN + LPA as compared to after stimulation with either alone. Tyrosine-phosphorylated paxillin comprised 2 components; slowly and fast migrating ones. Immunoblotting of anti-paxillin immunoprecipitates with phosphorylation site-specific Abs revealed the following: tyrosine-phosphorylation was enhanced preferentially on a slowly migrating component after stimulation with FN + LPA; this component contained phosphorylation at both tyrosine residue (Y) 31 and Y118; and phosphorylation of paxillin at Y181 was constitutive and not augmented by stimulation with either FN or LPA. Amiloride, an inhibitor of the Na+/H+ antiporter downstream of ROCK, suppressed cell motility and correspondingly paxillin tyrosine-phosphorylation at both Y31 and Y118. Paxillin phosphorylation weakly induced by FN alone, insufficient for cell migration, was not inhibited by amiloride. These results demonstrate that LPA collaborates with FN for persistent tyrosine phosphorylation of paxillin at both Y31 and Y118, regulated by the Na+/H+ antiporter downstream of ROCK and that this phosphorylated paxillin is essential for MM1 cancer cell migration.

The Arabidopsis floral homeotic gene PISTILLATA is regulated by discrete cis-elements responsive to induction and maintenance signals. PISTILLATA is a B-class floral organ identity gene required for the normal development of petals and stamens in Arabidopsis. PISTILLATA expression is induced in the stage 3 flowers (early expression) and is maintained until anthesis (late expression). To explore in more detail the developmentally regulated gene expression of PISTILLATA, we have analyzed the PISTILLATA promoter using uidA (beta)-glucuronidase gene) fusion constructs (PI::GUS) in transgenic Arabidopsis. Promoter deletion analyses suggest that early PISTILLATA expression is mediated by the distal region and that late expression is mediated by the proximal region. Based on the PI::GUS expression patterns in the loss- and gain-of-function alleles of meristem or organ identity genes, we have shown that LEAFY and UNUSUAL FLORAL ORGANS induce PISTILLATA expression in a flower-independent manner via a distal promoter, and that PISTILLATA and APETALA3 maintain PISTILLATA expression (autoregulation) in the later stages of flower development via a proximal promoter. In addition, we have demonstrated that de novo protein synthesis is required for the PISTILLATA autoregulatory circuit.

Development of an introductory course in child protection. The maltreatment of children is a significant public health and social problem. Healthcare professionals have a crucial role to play working with other agencies to protect children from abuse and neglect. The need for training, support and clinical supervision in this work has been identified. This article discusses the collaborative work that led to the establishment of an introductory course in child protection (English National Board 970) at one school of nursing and midwifery and outlines the benefits of undertaking such a course. The course has attracted participants from a range of healthcare settings and has proved to be well evaluated and oversubscribed. Practitioners have returned to their work setting with increased awareness of child maltreatment and an understanding of the need for a proactive approach to child protection.

A novel technique to facilitate laparoscopic repair of large paraesophageal hernias. Laparoscopic repair of large paraesophageal hernias (LPEH) is technically challenging, and requires advanced laparoscopic skills. We have developed a novel technique for facilitating laparoscopic repair of LPEHs safely and easily, using a Nelaton catheter. Seven patients with LPEHs were operated on through a laparoscopic approach. During surgery, the left lobe of the liver and right diaphragmatic crus were elevated using a suspended thread covered by a Nelaton catheter. All patients were operated on laparoscopically using this technique. No patient required conversion to open method. The median operating time was 205 minutes and the range was from 155 to 295 minutes. No intraoperative or early complications occurred in any patient. Late complications occurred in 2 patients due to a small sliding hernia: a slipped fundoplication in 1 patient, and a gastric ulcer in the other. In conclusion, laparoscopic repair of LPEH is a challenging procedure that requires wide experience in laparoscopic gastroesophageal surgery. Further refinement for this operation may be necessary.

Inhaled particles and respiratory disease. This brief discussion of inhaled particles, their manner of deposition and clearance, and their association with many human disease has been designed to remind us of the importance of particulate agents as sensitizers, via their allergen content, as causative agents of lung inflammation via their immunotoxic properties, as inducers of inflammatory alveolitis based on their content of antigens and adjuvant-like material, and as infectious agents. All these properties can play a part in a wide variety of allergic parenchymal, infectious, and industrial lung diseases and in building-related illnesses.

Hemobilia: a case with recurrent jaundice cured by removal of a blood clot from the common bile duct. A 78-year-old woman was admitted for recurrent jaundice, fever and biliary colic. At operation the common duct was found to be filled with a large blood clot. Removal of this clot resulted in a clinical cure.

Erythropoietin attenuates apoptosis after ischemia-reperfusion-induced renal injury in transiently hyperglycemic Wister rats. Hyperglycemia is associated with a decreased tolerance to ischemia and an increased severity of renal ischemia reperfusion (I/R) injury. It has been suggested that erythropoietin (EPO) attenuates this effect in normoglycemic animals. This study sought to examine the effects of EPO on treatment renal I/R injury (IRI) in transiently hyperglycemic rats. Twenty-eight male Wister rats anesthetized with isoflurane received glucose (2.5 g.kg(-1) intraperitoneally) before right nephrectomy. They were randomly assigned to four groups: sham operation (S); IRI (ISO); IRI+EPO, (600 UI kg(-1) low-dose EPO [EL]); and IRI+EPO 5000 UI kg(-1) (high-dose EPO [EH]). IRI was induced by a 25-minute period of left renal ischemia followed by reperfusion for 24 hours. Serum creatinine and glucose levels were measure at baseline (M1), immediately after the ischemic period (M2), and at 24 hours after reperfusion (M3). After sacrificing the animals, left kidney specimens were submitted for histological analysis including flow cytometry to estimate tubular necrosis and the percentages of apoptotic, dead or intact cells. Scr in the ISO group was significantly higher at M3 than among the other groups. Percentages of early apoptotic cells in ISO group were significantly higher than the other groups. Percentages of late apoptotic cells in S and ISO groups were significantly greater than EL and EH groups. However, no significant intergroup differences were observed regarding the incidence of tubular necrosis. Our results suggested that, although not preventing the occurrence of tubular necrosis, EPO attenuated apoptosis and glomerular functional impairment among transiently hyperglycemic rats undergoing an ischemia/reperfusion insult.

Derivation of human embryonic stem cell line Genea019. The Genea019 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, through ICM outgrowth on inactivated feeders. The line showed pluripotent cell morphology and genomic analysis verified a 46, XX karyotype, female Allele pattern and unaffected Htt CAG repeat length, compared to HD affected sibling Genea020. Pluripotency of Genea019 was demonstrated with 75% of cells expressing Nanog, 89% Oct4, 48% Tra1-60 and 85% SSEA4, a Pluritest Pluripotency score of 22.97, Novelty score of 1.42, tri-lineage teratoma formation and Alkaline Phosphatase activity. The cell line was negative for Mycoplasma and any visible contamination.

Combined phacoemulsification and XEN45 surgery from a temporal approach and 2 incisions. To assess the safety and effectiveness of phacoemulsification combined with XEN45 implant surgery in patients with cataract and open-angle glaucoma, with 12-month follow-up. A prospective study conducted on 30 eyes requiring phacoemulsification with, at least, 2 medications to control intraocular pressure (IOP). Phacoemulsification combined with XEN45 implant surgery was performed within 15minutes of administering subconjunctival mitomycin C. Surgery was performed through 2 temporal incisions, separated by 90°, using the inferior to enter the XEN45 and to implant it in the superior nasal region. A record was made of the best corrected visual acuity, IOP before and 1 day, 1 month, 3 months, 6 months, 9 months, and 12 months after surgery, the number of antiglaucomatous medications, and complications. The best corrected visual acuity was 0.37±0.2 and 0.72±0.15 before and 12 months after surgery, respectively. The pre-operative IOP was 21.2±3.4mmHg, with 3.07 drugs, decreasing by 61.65% on the first day, 37.26% at 1 month, 35.05% at 3 months, 31% at 6 months, 30.6% at 9 months, and 29.34% at 12 months. The number of medications decreased by 94.57%. Complications occurred in 3 eyes, 2 of them were excluded because we could not complete the implantation (280° subconjunctival haemorrhage and XEN extrusion when trying to reposition). In a third case, the bleb was encapsulated at 5 months after surgery. The phacoemulsification combined with XEN45 implant surgery can effectively reduce IOP and the number of drugs in mild-moderate open-angle glaucoma, as they rehabilitate the VA. The use of only 2 micro-invasive incisions makes it simple, quick and safe, with few complications at 12 months follow-up from surgery.

Mechanisms of antimelanoma effect of oat β-glucan supported by electroporation. There are still not specified mechanisms how beta-glucan molecules are transported into cells. Supposing, beta-glucan toxicity against tumor cells may be related to the overexpression of the transporter responsible for the transport of glucose molecules in the cells. In this case, glucans - polymers composed of glucose units are much more up-taken by tumor than normal cells. Increased GLUT1 (Glucose Transporter Type 1) expression has been demonstrated earlier in malignant melanomas. GLUT1 expression promotes glucose uptake and cell growth in that cells. Also, in human melanoma tissues a significant correlation between GLUT1 expression and mitotic activity was found. The aim of the study was to verify if oat β-glucan (OβG) is delivered into cells by GLUT-1 membrane protein. To check it out we blocked GLUT1 transporters by an inhibitor WZB117 and then we investigated cells viability with and without reversible electroporation (EP). The obtained results bring us to elucidate the mechanism of transport of the OβG into the cells is GLUT-1 dependent and moreover can be supported by EP method.

Effect of ion-exchange treatment on mechanical properties of new dental ceramics. To examine whether the ion exchange strengthening can be achieved for several new ceramics such as glass ceramics or castable ceramics. The ceramics selected for this study were three porcelains and three castable ceramics. 60 bend bars of the respective ceramics (1 x 5 x 10 mm) were fabricated according to the respective manufacturer's directions. Finally, the respective specimens were polished up to 0.1 microm and then divided into two groups: one was coated with an ion-exchange paste and the other was not treated as the control. Then, for the respective ceramics the hardness, flexural strength and fracture toughness were investigated and compared to the control. Although the ion-exchange treatment significantly (P < 0.05, Scheffé's test) increased flexural strength and fracture toughness for the porcelain based ceramics, it did not increase these properties for the castable ceramics. The chemical treatment did not affect hardness for any of the specimens.

'All foods affect health': understandings of functional foods and healthy eating among health-oriented Finns. One of the recent phenomena in contemporary discussion of eating is 'functional foods', i.e. foods marketed as promoting health or reducing the risk of disease. This article analyses lay understandings of health-promoting foods in Finland by examining the ways in which middle-aged health-oriented consumers make sense of functional foods in the context of healthy eating. The article is based on an analysis of eight focus group discussions held with 45 users and non-users of cholesterol-lowering products as specific type of functional foods. The findings indicate that consumers interpret functional foods and healthy eating from a variety of perspectives. These perspectives include (1) focus on the whole diet, (2) distinguishing between healthy foods and functional foods, (3) the dilemma of eating for health or for pleasure, (4) healthfulness as an 'individual' issue and finally, (5) the duality of risk in the context of functional foods. The diversity of perspectives illustrates the ways that interpretations of functional foods and healthy eating are entangled with notions of uncertainties relating to scientific knowledge, moral undertones governing what is defined as acceptable eating and the symbolic significance of food as an inextricably social matter.

Prenatal diagnosis of total anomalous pulmonary venous connection to the portal vein associated with right atrial isomerism. We report the prenatal diagnosis of total anomalous pulmonary venous connection to the portal system in a 20-week fetus with right atrial isomerism. The apex of the fetal heart pointed to the left, the fetal stomach was on the right, there was a common atrioventricular valve, the left ventricle was small and the abdominal aorta and inferior vena cava were on the left side; all these features were suggestive of right atrial isomerism. An anomalous vein was connected to the portal vein which ascended above the diaphragm and ended in a confluence of pulmonary veins, posterior to the common atrium. Color Doppler imaging helped confirm the diagnosis of total anomalous pulmonary venous connection. The prenatal findings were confirmed on autopsy.

Circulating anticoagulant phenomenon manifesting as isolated intracranial hypertension. A 28 years old male developed headache and bilateral papilloedema. Cerebrospinal fluid revealed increased opening pressure, but was otherwise unremarkable. Magnetic Resonance (MRI) imaging of the brain was normal; MRI of the neck disclosed thrombosis of the right internal jugular vein. Russel viper venom test revealed the presence of a circulating anticoagulant.

"Voices of the broken body." The resumption of non-professional female players' sports careers after anterior cruciate ligament injury. The female player's dilemma: is she willing to run the risk? The article takes as its starting point the lived experiences of female sports patients in rehabilitation. The research data are semi-structured qualitative interviews (N=17) with non-professional female players as patients, having anterior cruciate ligament injuries (ACL-injuries). Injury narratives have been conducted, with a focus upon how female handball players managed the injured situation. Ethnographic research was taken in a private physiotherapy clinic over a period of more than 1 (1/2) years. The narratives show the impact of risk management - the individual coping strategy of the players. The handball her-player has choices to make regarding the resumption of the career. The options and possibilities of playing or not playing after an ACL-injury are connected to the trust in the capacity of the body. The concept of bodily risk reflexive coping strategy is constructed to understand the question of the resumption of the career. The individualistic self-care management indicates a manageable body with a desire to act as worthy of being a full part of the sporting society. This strategy is adding to the sense of accomplishment and to the continuing development of self-identity. The study shows that there is a need for guidance in the injury process. Playing is connected with pleasurable feelings and excitements, but the her-player does care for the bodily self and her risk assessment is so far not a "misuse" or a consumption of sports medicine in the name of sporting achievements.

White matter tract and glial-associated changes in 5-hydroxymethylcytosine following chronic cerebral hypoperfusion. White matter abnormalities due to age-related cerebrovascular alterations is a common pathological hallmark associated with functional impairment in the elderly which has been modeled in chronically hypoperfused mice. 5-Methylcytosine (5mC) and its oxidized derivative 5-hydroxymethylcytosine (5hmC) are DNA modifications that have been recently linked with age-related neurodegeneration and cerebrovascular pathology. Here we conducted a pilot investigation of whether chronic cerebral hypoperfusion might affect genomic distribution of these modifications and/ or a Ten-Eleven Translocation protein 2 (TET2) which catalyses hydroxymethylation in white and grey matter regions of this animal model. Immunohistochemical evaluation of sham and chronically hypoperfused mice a month after surgery revealed significant (p<0.05) increases in the proportion of 5hmC positive cells, Iba1 positive inflammatory microglia, and NG2 positive oligodendroglial progenitors in the hypoperfused corpus callosum. In the same white matter tract there was an absence of hypoperfusion-induced alterations in the proportion of 5mC, TET2 positive cells and CC1 positive mature oligodrendrocytes. Correlation analysis across animals within both treatment groups demonstrated a significant association of the elevated 5hmC levels with increases in the proportion of inflammatory microglia only (p=0.01) in the corpus callosum. In vitro studies revealed that 5hmC is lost during oligodendroglial maturation but not microglial activation. Additionally, TET1, TET2, and TET3 protein levels showed dynamic alterations during oligodendroglial development and following oxidative stress in vitro. Our study suggests that 5hmC exhibits white matter tract and cell type specific dynamics following chronic cerebral hypoperfusion in mice.

Can marked hyperglycemia occur without ketosis? The significance of ketosis in this syndrome has been evaluated from several viewpoints. With respect to acid-base considerations (pH, anion gap), ketosis was not very significant. However, with respect to sustained hyperglycemia, the combustion of less glucose than normal by the brain is critical and it is likely that ketone body metabolism plays an important role in this regard. This point can be underscored by a quantitative example. First, assume that the maximum rate of new glucose production in a fasted subject is less than 100 g of glucose per day. Second, since the brain will burn 100 g of glucose per day in a non-ketotic subject, it follows that, even in the absence of glucosuria, there will be a net daily consumption of glucose. Since the hyperglycemic individual has only an extra 100 or so g of glucose, it follows that the blood glucose concentration would approach the renal threshold in several days in the absence of ketosis. Recall that this is a minimum estimate because glucose oxidation in other organs and glucosuria will remove an additional quantity of glucose. Hyperglycemia can only be maintained in the absence of glucose intake if there is a reduced rate of glucose metabolism in the brain. The brain can diminish its rate of glucose catabolism by several mechanisms, including a diminished metabolic rate in the brain and/or the consumption of non-glucose fuels (free fatty acids or beta-hydroxybutyrate) by this organ.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute rheumatic fever in American Samoa. Acute rheumatic fever is common among Samoans in Hawaii. During 2 visits to evaluate the magnitude of rheumatic fever problem among Samoans in American Samoa, we identified 148 patients with rheumatic fever on penicillin prophylaxis. Retrospective chart reviews were done showing possible delays in diagnosis of acute rheumatic fever.

Refractory periodontitis associated with abnormal polymorphonuclear leukocyte phagocytosis and cigarette smoking. To learn if refractory periodontitis may be associated with defects in peripheral blood polymorphonuclear leukocyte (PMN) function, phagocytosis and chemotaxis were analyzed in 31 otherwise healthy patients and 12 unaffected controls. When compared to controls, no chemotactic defects to 10 nM f-Met-Leu-Phe (fMLP) were detected. In contrast, phagocytosis was significantly impaired (P < 0.001). The mean rates of adhesion and ingestion of opsonized Staphylococcus aureus by PMNs were 7.1 +/- 1.7 (+/- SD) and 1.4 +/- 0.5 bacteria/100 PMNs/minute respectively for patients, and 11.0 +/- 2.4 and 3.1 +/- 0.6 for unaffected, healthy controls. While the quality of oral hygiene and access to dental care were high, a retrospective search for associated environmental variables showed that 90% (28 of 31) of the refractory patients were smokers. The frequency of smokers is particularly striking, since only 21% of adults in Minnesota use tobacco regularly. These data suggest that there is a strong association between a peripheral blood PMN defect and refractory periodontitis. Furthermore, these studies suggest that tobacco use may contribute to this association.

Cerebrospinal fluid markers in relation to outcome in patients with global cerebral ischemia. To investigate the possibility of improving the accuracy of prognostication in early hypoxic brain damage, 12 patients with global cerebral ischemia (GCI) due to circulatory arrest outside hospital were followed until death or for 1 yr. Five who survived for more than 2 weeks displayed better values on coma scoring from 16 h-3 days, compared to those who succumbed within 2 weeks. In 2 week-survivors, lumbar puncture revealed consistently lower adenylate kinase (AK) activity in cerebrospinal fluid (CSF) at 24 h than in the other patients, whereas glutathione and lactate values overlapped to some degree. The CSF-AK activity at 48--72 h was less correlated to clinical outcome. It is concluded that the results from coma scoring, based upon clinical observation, and from determination of AK activity in CSF at 24 h reinforce each other in discriminative power to predict prognosis in these patients.

Closure of large pharyngo-oesophageal fistulas with free flap transfer after resections for cancer. Postoperative salivary fistulas still remain a serious and potentially lethal problem in head and neck reconstruction particularly if the fistula is large and involving one half or more of the circumference of the pharyngo-oesophagus. Pedicled flaps have traditionally been the flaps of choice for closure of these fistulas, but the results are often disappointing. During the period 1982 to 1995, we have used either a radial forearm free flap or a jejunal free flap to close large and complex pharyngo-oesophageal fistulas after resection for cancer in 15 patients. Although two patients developed major fistulas that required additional operations for closure, successful closure was achieved in all but one case: the success rate was therefore 14/15 (93%). We consider that jejunal flaps are suitable for circumferential pharyngo-oesophageal reconstruction and forearm flaps for non-circumferential defects.

Association between achieving treatment goals for lipid-lowering and cardiovascular events in real clinical practice. There is substantial evidence that treatment with lipid-lowering agents can decrease cardiovascular morbidity and total mortality in patients with elevated serum lipid values and/or prior ischaemic heart disease. However, only a minority of these high-risk patients are believed to receive treatment, and among those who do receive pharmaceutical treatment the majority do not reach the therapeutic goal. Our goal was to investigate if this translates to a higher risk of cardiovascular events in real clinical practice. A retrospective cohort study using linkage of electronic medical records, the Swedish national inpatient registry and cause of death registry was performed, enrolling a total of 4976 patients who received treatment with a lipid-lowering agent at any time between 1 January 1993 and 1 December 2001. Cox proportional hazards regression was used to evaluate the impact of goal attainment along with potential confounding factors. Patients who reached treatment goals were 24% less likely to suffer a cardiovascular event (relative risk: 0.76, 95% confidence interval: 0.60-0.96) than patients who did not reach treatment goals. A substantial proportion of patients treated with lipid-lowering agents do not achieve the treatment goals. Failure to reach treatment goals translates into a higher risk of cardiovascular events, and it is thus of importance to ensure that patients reach goals.

High HDL cholesterol level after treatment with pitavastatin is an important factor for regression in carotid intima-media thickness. This study is a prospective multicenter study designed to investigate the effects of lipid-lowering therapy with pitavastatin on atherosclerotic plaque in patients with coronary heart disease, and to determine which factor is more closely associated with plaque regression. Participants (n = 63) were treated with pitavastatin for 12 months, and the carotid intima-media thickness (IMT) was measured by ultrasound before and after treatment. Mean IMT slightly but significantly decreased (from 0.99 ± 0.33 to 0.94 ± 0.28 mm for overall, P = 0.01) regardless of the presence of pretreatment with other statins. There were no significant relations with hs-CRP, malondialdehyde-LDL, LDL cholesterol, and smaller LDL cholesterol levels despite their decrease by pitavastatin. Decreases in mean IMT were observed significantly more frequently in subjects with high on-treatment HDL cholesterol levels than with low HDL cholesterol levels (P = 0.017). The change in mean IMT tended to be inversely correlated with increments in HDL cholesterol and apolipoprotein A-I. The IMT regression was more often observed in the absence of diabetes and metabolic syndrome. In conclusion, we demonstrated that treatment with pitavastatin attenuated atherosclerotic plaque. This effect was associated with the level of HDL cholesterol, and was stronger in the absence of diabetes and metabolic syndrome in our ischemic heart disease patients.

On the TD-DFT accuracy in determining single and double bonds in excited-state structures of organic molecules. We present an analysis on the behavior of the TD-DFT approach in the determination of excited-state structures with particular attention to single and double bonds. The analysis is based on a direct comparison with the highly correlated CASPT2 ab initio approach. Six DFT exchange-correlation functionals differing in the Hartree-Fock exchange percentage and the type of correlation functional are considered and applied to the study of seven prototype organic molecules characterized by two families of excitations (acrolein, acetone, diazomethane, and propanoic acid anion for n-π* and cis-1,3-butadiene, trans-1,3-butadiene, and pyrrole for π-π*), and three protonated Schiff bases, used as model chromophores for 11-cis retinal. Our analysis allows pinpointing specific correlations between accuracy of the various functionals and category of excitation and/or type of chemical bond involved in the corresponding geometry relaxation. We confirm the role of the long-range correction of the potential to obtain a balanced description of excitation energies and excited-state structures, but we also point out that, for a small system, B3LYP and PBE0 also give results close to CASPT2.

Geographic variations in the prevalence rates of Parkinson's disease in Alberta. Parkinson's disease prevalence rates were examined for the Province of Alberta by age, sex and census division. Using the claims administrative data from the Alberta Health Care Insurance Plan, a cohort of all registered individuals (2.4 million) was extracted and followed for the five year period, April 1, 1984 to March 31, 1989. No new members were added to the cohort and an attrition rate averaging 6% per year was observed. The overall crude prevalence rates of 248.9 and 239.8 per 100,000 population were noted for males and females respectively. Both sexes were found to have a statistically significant variation across Alberta's 19 census divisions. For males, examination of standardized morbidity ratios found a low risk of Parkinson's disease associated with five census divisions, of which two contained Alberta's two largest cities. An excess risk was associated with four primarily rural census divisions. Females, on the other hand, had a low risk associated with one rural census division and excess risk in four census divisions. The uneven distribution within Alberta offers support for an environmental theory of etiology which may be associated with rural living.

Effect of hamstrings muscle action on stability of the ACL-deficient knee in isokinetic extension exercise. To quantify the effect of hamstrings muscle action on stability of the anterior cruciate ligament deficient knee during isokinetic exercise at various speeds. Mathematical modeling and forward-dynamics computer simulation were used to study the interactions between knee-extension speed, hamstrings co-contraction activity, and anterior tibial translation in the intact and anterior cruciate deficient knee. There is much experimental evidence available to believe that hamstrings co-contraction can reduce anterior tibial translation in the anterior cruciate deficient knee. Little is known, however, about the level of hamstrings activation needed to keep anterior tibial translation within normal limits during functional activity. Isokinetic knee-extension was simulated with a sagittal-plane model used previously to study load sharing between the muscles, ligaments, and bones during isometric knee-extension exercise, isokinetic exercise, and squatting exercise. Some amount of hamstrings activation is needed to stabilize an anterior cruciate deficient knee irrespective of how fast the knee extends. The level of hamstrings co-contraction needed to stabilize an anterior cruciate deficient knee is inversely related to extension speed. Hamstrings co-contraction is more effective in reducing anterior tibial translation than low-resistance extension exercise. Excessive anterior tibial translation during knee-extension exercise may lead to damage of the meniscus and other passive structures inside the knee. If anterior cruciate deficient patients can be trained to co-contract their hamstrings during isokinetic knee-extension, then this exercise is appropriate for maintaining strength of the thigh muscles without compromising the anterior stability of the knee.

Type II Diabetes Mellitus Accelerates Age-Dependent Aβ Pathology in Cynomolgus Monkey Brain. Accumulating evidence suggests that diabetes mellitus (DM) is one of the strongest risk factors for developing Alzheimer's disease (AD). However, it remains unclear how DM accelerates AD pathology in the brain. Cynomolgus monkey (Macaca fascicularis) is one of the nonhuman primates used for biomedical research, and we can observe spontaneous formation of AD pathology, such as senile plaques (SPs) and neurofibrillary tangles (NFTs), with the advance of aging. Furthermore, obesity is occasionally observed and frequently leads to development of type II DM (T2DM) in laboratory-housed cynomolgus monkeys. These findings suggest that cynomolgus monkey is a useful species to study the relationship between T2DM and AD pathology. In T2DM-affected monkey brains, SPs were observed in frontal and temporal lobe cortices almost 5 years earlier than healthy control monkeys. Moreover, age-related endocytic pathology, such as intraneuronal accumulation of enlarged endosomes, was exacerbated in T2DM-affected monkey brains. Since accumulating evidences suggest that endocytic dysfunction is involved in Aβ pathology, T2DM may aggravate age-related endocytic dysfunction, leading to the acceleration of Aβ pathology.

Identification of inhibitors of urinary alanine aminopeptidase. Amino acids and ammonia were identified as natural inhibitors of urinary AAP. In urines from healthy volunteers approximately one half of the inhibition could be accounted for by amino acids and ammonia. At the measured concentrations, histidine, ammonia and phenylalanine, in decreasing order, were the most effective inhibitors. Results from kinetic studies with amino acids added to gel-filtered urine are consistent with the presence of two AAP isoenzymes with different inhibition characteristics. The ten amino acids which were tested show the same inhibition kinetics. Differences between amino acids are quantitative.

A fully integrated passive microfluidic Lab-on-a-Chip for real-time electrochemical detection of ammonium: Sewage applications. The present work reports on the development of a new generation of Lab-on-a-chip (LOC) to perform in-situ and real-time potentiometric measurements in flowing water. The device consisted of two differentiated parts: a poly (dimethylsiloxane) (PDMS) microfluidic structure obtained by soft lithography and a fully integrated chemical sensing platform including four working microelectrodes, two reference microelectrodes and one counter microelectrode for detecting ammonium in a continuous mode. The performance of the device was evaluated following its potentiometric response when analyzing ammonium containing samples. As a key parameter, its time of response was compared to that of a commercially available electrical conductivity sensor used as reference sensor during tests in laboratory using flowing tap water and technical scale using flowing wastewater. As a result, the LOC showed a slope of 55 mV/decade, a limit of detection of 4·10-5 M and a time of full response between 10 and 12 s. It was demonstrated that the device can provide fast and reliable data at real time when immersed in a laminar flow of water. Moreover, the test of robustness showed that it was still functional after immersion in sewage for at least 15 min. Besides, the LOC reported here can be helpful for a wide variety of flowing-water applications such as aqua culture outlets control, in-situ and continuous analysis of rivers effluents and sea waters monitoring among others.

The use of chemiluminescence and the ELISA spot assay to identify and enumerate rare immunoglobulin switch variants. The use of chemiluminescence and the ELISA spot assay for identifying rare immunoglobulin switch variants is described. The technique utilizes nitrocellulose membranes and allows rapid screening of a large number of cells. The number of spots can be recorded either manually or automatically by using a commercially available colony counting program. This modification of the ELISA spot assay makes it less labor intensive and time consuming and can be adapted for the search for rare cells secreting small amounts of Ig or other macromolecules.

High concentrations of cannabinoids activate apoptosis in human U373MG glioma cells. Cannabinoids bind to two G-protein-coupled receptors, CB1 and CB2, expressed by neurons and cells of the immune system, respectively. Glioma cells (astrocyte-derived brain tumor cells) express cannabinoid receptors, and numerous in vitro and in vivo studies performed in rodents have concluded that apoptosis could be induced by cannabinoids in these cells. Whether this also applies to human cells is controversial; we, therefore, assessed the effect of cannabinoids on human glioma cell viability with the human astrocytoma cell line U373MG. We report here that U373MG human glioma cells are sensitive only to high concentrations of cannabinoids (>5 microg/ml for Delta(9)-THC). Similar concentrations of the compounds promoted a rapid activation of extracellular-regulated kinase and c-Jun NH2-terminal kinase, suggesting that cannabinoid receptors are functional in U373MG cells. Nevertheless, these kinases are not involved in cannabinoid-induced cell death in U373MG cells, insofar as blocking their activation with specific inhibitors does not reduce cell death. CB1 is expressed in U373MG cells and is involved in cannabinoid-induced cell death, in that blocking its activation with a specific antagonist (AM251) almost totally prevented cell death following incubation of the cells with Delta(9)-THC. In addition, as already reported, some cannabinoids may have modest proproliferative properties in U373MG cells. Human U373MG glioma cells are sensitive only to very high, pharmacologically irrelevant concentrations of cannabinoids, so it seems unlikely that cannabinoids would constitute promising molecules for treating malignant astrocytoma; they do not induce glioma cell death at doses that could be applied safely to humans.

Presenilin I interaction with cytoskeleton and association with actin filaments. Presenilin I (PSI) has been shown to interact with microfilament-associated proteins of the filamin family. Here, we investigated a possible association of PSI with the cytoskeleton. Immunoblotting of detergent-insoluble fractions of rat brain homogenate revealed enrichment of neuron-specific 36 and 14 kDa proteolytic fragments of PSI, whereas 30 and 20 kDa fragments were found in the detergent-soluble fraction. Specific severing of microfilaments with gelsolin in the detergent-insoluble pellet and subsequent centrifugation led to the detection of both actin and PSI fragments in the supernatant. In addition, in vitro translated PSI cosedimented with actin filaments. Our findings provide biochemical evidence for the association of PSI fragments with actin filaments.

Rapid and selective sampling of IgG from skin in less than 1 min using a high surface area wearable immunoassay patch. Microprojection array (MPA) patches are an attractive approach to selectively capture circulating proteins from the skin with minimal invasiveness for diagnostics at the point-of-care or in the home. A key challenge to develop this technology is to extract sufficient quantities of specific proteins from within the skin to enable high diagnostic sensitivity within a convenient amount of time. To achieve this, we investigated the effect of MPA geometry (i.e. projection density, length and array size) on protein capture. We hypothesised that the penetrated surface area of MPAs is a major determinant of protein capture however it was not known if simultaneously increasing projection density, length and array size is possible without adversely affecting penetration and/or tolerability. We show that increasing the projection density (5000-30,000 proj. cm-2) and array size (4-36 mm2) significantly increases biomarker capture whilst maintaining of a similar level tolerability, which supports previous literature for projection length (40-190 μm). Ultimately, we designed a high surface area MPA (30,000 proj. cm-2, 36 mm2, 140 μm) with a 4.5-fold increase in penetrated surface area compared to our standard MPA design (20,408 proj. cm-2, 16 mm2, 100 μm). The high surface area MPA captured antigen-specific IgG from mice in 30 s with 100% diagnostic sensitivity compared with 10-30 min for previous MPA immunoassay patches, which is over an order of magnitude reduction in wear time. This demonstrates for the first time that MPAs may be used for ultra-rapid (<1 min) protein capture from skin in a time competitive with standard clinical procedures like the needle and lancet, which has broad implications for minimally invasive and point-of-care diagnostics.

Approach to the Assessment and Management of Adult Patients With Atopic Dermatitis: A Consensus Document. Section IV: Treatment Options for the Management of Atopic Dermatitis. The objectives of therapy for atopic dermatitis (AD) are to reduce skin inflammation and pruritus, restore skin barrier function, and improve quality of life (QoL). Treatments can be classified as moisturizing and basic care, topical therapy, phototherapy, and systemic therapy. In this review, we summarize the treatments for AD and recommendations for their use.

Differential regulation of immediate-early gene expression in the prefrontal cortex of rats with a high vs low behavioral response to methamphetamine. Methamphetamine (METH) administration mimics many of the symptoms of mania and can produce psychosis after chronic use. Both rodents and man display interindividual variation in response to METH. The molecular mechanisms underlying these differences might be relevant to both stimulant addiction and endogenous psychosis. We treated 50 Sprague-Dawley rats acutely with METH (4.0 mg/kg) and 10 control rats with saline, and measured their behavior for 3 h after drug administration. Animals were divided into high responders (HR) (top 20%) and low responders (LR) (lowest 20%) based on their stereotypy response. They were killed 24 h after injection. Total RNA was extracted from the prefrontal cortex (PFC) and the expression of approximately 30 000 transcripts were analyzed using Affymetrix 230 2.0 GeneChips. Real-time reverse transcription-polymerase chain reaction was used to validate the expression of a select group of genes. Forty-three genes exhibited significant differences in expression in HR vs LR 24 h after METH treatment including a group of immediate-early genes (IEGs) (eg, c-fos, junB, NGFI-B, serum-regulated glucocorticoid kinase). These IEG expression differences were accompanied by the significant downregulation of many of these genes compared to saline in the HR but not LR, suggesting a differential responsiveness of signal transduction pathways in these two groups of rats. In addition, the expression of other transcription factors in the PFC was significantly different in HR compared to LR. These gene expression changes may contribute to individual differences in responsiveness to stimulants and the development of mania and psychosis.

Obsessive-compulsive symptoms in panic disorder. Previous reports have noted an increased prevalence of obsessive-compulsive symptoms in patients with panic disorder. The authors found a prevalence of obsessive-compulsive symptoms in 19 (27%) of 70 patients with panic disorder. Compared to a subgroup of 25 patients with classic features of panic disorder and no obsessive-compulsive symptoms, the subgroup with obsessive-compulsive symptoms had an earlier onset of illness, were more likely to have personal and family histories of major depression and substance abuse, and showed a poorer outcome after treatment.

Interrelationship between ovine follicular fluid inhibin and serum albumin. Ovine follicular fluid inhibin (oFF-I) as isolated in this laboratory, proved to be a monomeric protein (M(r).65 kDa). It was found to share very many of the physico-chemical characteristics of ovine serum albumin (oSA)-such as molecular size, iso-electric point, N-terminal aminoacid, finger-print patterns following enzymatic or cyanogen bromide cleavage, as well as binding of estradiol-17 beta and tryptophan. Furthermore, an antiserum containing polyclonal antibodies to oSA showed perfect cross-reaction with oFF-I. Nevertheless, oFF-I is distinct and different from oSA, as would be evident from the data reported here. Of the two proteins, oFF-I alone is capable of suppressing pituitary FSH output in a dose-dependent manner. Secondly, an antiserum containing polyclonal antibodies against Fraction-S2, a partially purified, biologically active fragment (M(r): 30-40 kDa)-derived from oFF-I, cross-reacted with the 65 kDa inhibin, but did not recognize oSA. Finally, the CD-spectra of the two proteins, when examined as a function of pH, show characteristic differences.

Short-time growth of a Kardar-Parisi-Zhang interface with flat initial conditions. The short-time behavior of the (1+1)-dimensional Kardar-Parisi-Zhang (KPZ) growth equation with a flat initial condition is obtained from the exact expressions for the moments of the partition function of a directed polymer with one end point free and the other fixed. From these expressions, the short-time expansions of the lowest cumulants of the KPZ height field are exactly derived. The results for these two classes of cumulants are checked in high-precision lattice numerical simulations. The short-time limit considered here is relevant for the study of the interface growth in the large-diffusivity or weak-noise limit and describes the universal crossover between the Edwards-Wilkinson and the KPZ universality classes for an initially flat interface.

The surge of predatory open-access in neurosciences and neurology. Predatory open access is a controversial publishing business model that exploits the open-access system by charging publication fees in the absence of transparent editorial services. The credibility of academic publishing is now seriously threatened by predatory journals, whose articles are accorded real citations and thus contaminate the genuine scientific records of legitimate journals. This is of particular concern for public health since clinical practice relies on the findings generated by scholarly articles. Aim of this study was to compile a list of predatory journals targeting the neurosciences and neurology disciplines and to analyze the magnitude and geographical distribution of the phenomenon in these fields. Eighty-seven predatory journals operate in neurosciences and 101 in neurology, for a total of 2404 and 3134 articles issued, respectively. Publication fees range 521-637 USD, much less than those charged by genuine open-access journals. The country of origin of 26.0-37.0% of the publishers was impossible to determine due to poor websites or provision of vague or non-credible locations. Of the rest 35.3-42.0% reported their headquarters in the USA, 19.0-39.2% in India, 3.0-9.8% in other countries. Although calling themselves "open-access", none of the journals retrieved was listed in the Directory of Open Access Journals. However, 14.9-24.7% of them were found to be indexed in PubMed and PubMed Central, which raises concerns on the criteria for inclusion of journals and publishers imposed by these popular databases. Scholars in the neurosciences are advised to use all the available tools to recognize predatory practices and avoid the downsides of predatory journals.

The benefit of adding a physiotherapy or occupational therapy intervention programme to a standardized group-based interdisciplinary rehabilitation programme for patients with chronic widespread pain: a randomized active-controlled non-blinded trial. To evaluate the benefit of adding occupational therapy or physiotherapy interventions to a standard rehabilitation programme targeted for chronic widespread pain. Randomized active-controlled non-blinded trial. Women with chronic widespread pain recruited in a tertiary outpatient clinic. Participants were randomized to a two-week, group-based standard rehabilitation programme followed by 16 weeks of group-based occupational therapy (Group BOT, n = 43) or 16 weeks of group-based physiotherapy (Group BPT, n = 42). Group A only received the two-week rehabilitation programme acting as comparator (n = 96). Primary outcomes were the Assessment of Motor and Process Skills and Short Form-36 (SF36) Mental Component Summary score. Mean changes in motor and process ability measures were clinically and statistically insignificant and without differences across the three groups assessed 88 weeks from baseline. Motor ability measures: -0.006 (95% confidence interval (CI): -0.244 to 0.233) in Group BOT; -0.045 (95% CI: -0.291 to 0.202) in Group BPT; and -0.017 (95% CI: -0.248 to 0.213) in Group A, P = 0.903. Process ability measures: 0.087 (95% CI: -0.056 to 0.231) in Group BOT; 0.075 (95% CI: -0.075 to 0.226) in Group BPT; and 0.072 (95% CI: -0.067 to 0.211) in Group A, P = 0.924. Mean changes in patient-reported outcomes were likewise small; clinically and statistically insignificant; and independent of group allocation, except for the SF36 mental component summary score in the BPT group: 8.58 (95% CI: 1.75 to 15.41). Participants were on average stable in observation-based measures of functional ability and patient-reported outcomes, except in overall mental well-being, favouring the enhanced intervention. Efficacy of additional interventions on functional ability remains uncertain.

Newly synthesized glycoconjugates from two cell lines derived from rat osteogenic sarcoma: effects of Matrigenin activity from bone. An activity isolated from bovine bone was previously shown to stimulate proteoglycan synthesis by several connective tissue cell lines from normal tissues (Matrigenin activity). The effect of this activity on glycoconjugate synthesis by two osteoblastic cell lines, ROS 17/2 and UMR-106, derived from rat osteogenic sarcoma, was examined after labelling of the cells with [3H]glucosamine and [35S]sulfate. The glycoconjugates from the cell layers and the media were separated by DEAE-Sephacel chromatography and the anionic glycoconjugates of the media were further analyzed by chromatography on Sepharose CL-2B and enzymatic digestion of the papain-released glycosaminoglycans. The ROS 17/2 cells secreted at least two distinct species of proteoglycan (one heparan sulfate rich and the other chondroitin sulfate rich), whereas the UMR-106 secreted primarily an anionic glycoprotein. The addition of Matrigenin activity to the ROS 17/2 cells resulted in stimulation of incorporation of radioactivity into the proteoglycan and hyaluronic acid, but in UMR-106 cultures it resulted in decreased incorporation into the anionic glycoprotein. The decrease in incorporation into the anionic glycoprotein from the medium was shown, by alkaline beta-elimination, to have occurred mainly in the oligosaccharide fraction, relative to control cultures.

Emerging understanding of the advantage of small molecules such as hydroxypyridinones in the treatment of iron overload. Deferiprone, a hydroxypyridin-4-one, is effective at facilitating iron removal from iron overloaded patients, when administered orally. Some problems associated with deferiprone are discussed. Hydroxypyridinone analogues with improved distribution, metabolism and affinity for iron are described. In particular the "high pFe(3+)" hydroxypyridin-4-ones possess considerable clinical potential.

Tumor necrosis factor-alpha induces expression of monocyte chemoattractant JE via fos and jun genes in clonal osteoblastic MC3T3-E1 cells. The mechanism by which circulating monocytes are attracted to sites of bone remodeling is unknown. We now report that tumor necrosis factor-alpha (TNF-alpha), a potent osteotrophic cytokine, was stimulatory for expression of the monocyte chemoattractant JE gene in osteoblastic MC3T3-E1 cells. TNF-alpha stimulated this JE gene expression transcriptionally. The presence of JE gene product in conditioned medium of the cytokine-treated cells was evidenced by an immunoprecipitation assay with antiserum specific for JE/MCP-1. The stimulated JE gene expression was markedly inhibited by H-7, a potent inhibitor of protein kinase C. Phorbol 12-myristate 13-acetate induced the JE gene expression, and the cytokine-induced JE gene expression was down-regulated by the phorbol ester pretreatment. TNF-alpha induced expression of both early protooncogenes, c-fos and c-jun, in the cells. Antisense oligonucleotides to these oncogenes significantly inhibited the cytokine-induced monocyte chemotactic activity. Furthermore, curcumin, a specific inhibitor of c-jun/AP-1, markedly inhibited JE gene expression and monocyte chemotactic activity induced by the cytokine. These results suggest that TNF-alpha may contribute to the regulation of remodeling and inflammation of bone tissues through the JE gene product.

Microbial population profiles of the microflora associated with pre- and postharvest tomatoes contaminated with Salmonella typhimurium or Salmonella montevideo. To determine the microflora profiles of pre- and postharvest tomatoes contaminated with Salmonella montevideo or S. typhimurium DT104. Salmonella montevideo or S. typhimurium was inoculated onto the flowers of tomato plants with the microflora of the subsequent fruit examined using a combination of Source Carbon Utilization and 16S rDNA-PCR profiling. From 16S rDNA profiles it was evident that tomatoes derived from Salmonella inoculated plants harboured a different microbial population compared to nontreated controls. The same result was observed for tomatoes inoculated at postharvest and subsequently stored for 14 days at 15 degrees C. From sequencing analysis it was found that tomatoes derived from Salmonella inoculated plants but testing negative for the enteric pathogen, frequently harboured Enterobacter and Bacillus spp. In contrast, both bacterial types were not found associated with tomatoes testing positive for Salmonella. Salmonella introduced onto tomatoes at pre- or postharvest alters the composition of the microbial community. The presence of Enterobacter and Bacillus spp negatively affects the persistence of Salmonella on preharvest tomatoes. Salmonella appears to modify rather than become integrated into the microbial communities associated with tomatoes. Yet, the presence of antagonistic bacteria appears to reduce the persistence of the enteric pathogen.

Efficacy of various doses and schedules of second-generation tyrosine kinase inhibitors. Imatinib is one of the most potent cancer therapeutic agents identified to date. Before the introduction of this tyrosine kinase inhibitor (TKI), 5-year survival in chronic myeloid leukemia (CML) was approximately 40%-60%, but since the introduction of imatinib, overall survival has increased to approximately 90% for patients with chronic-phase disease. However, nearly one fifth of patients are intolerant or resistant to imatinib, resulting in patients with persistent or progressive disease. Recent research has identified a number of additional compounds that more efficiently inhibit the Abl tyrosine kinase and additional kinases that potentially play a role in imatinib resistance. The advent of dasatinib and nilotinib has provided additional options for patients with progressive disease. A number of phase II clinical trials have recently demonstrated that these second-generation TKIs are well tolerated and effective in patients with Philadelphia chromosome-positive (Ph+) leukemias. Recent clinical trial developments raise questions regarding the proper dosage and schedule of these newer agents as well as the timing of their use in the treatment of patients with CML. Additionally, the development of nonoverlapping resistance patterns with sequential drug exposure argues for the possibility of a drug selection scheme that might limit the development of resistant disease. As the era of personalized medicine has begun to take shape in the 21st century, the addition of newer TKIs might facilitate this trend in the treatment of Ph+ leukemias.

Modeling the time-intensity profile of solar flare generated particle fluxes in the inner heliosphere. It is possible to model the time-intensity profile of solar particles expected in space after the occurrence of a significant solar flare on the sun. After the particles are accelerated in the flare process, if conditions are favorable, they may be released into the solar corona and then into space. The heliolongitudinal gradients observed in the inner heliosphere are extremely variable, reflecting the major magnetic structures in the solar corona which extend into space. These magnetic structures control the particle gradients in the inner heliosphere. The most extensive solar particle measurements are those observed by earth-orbiting spacecraft, and forecast and prediction procedures are best for the position of the earth. There is no consensus of how to extend the earth-based models to other locations in space. Local interplanetary conditions and structures exert considerable influence on the time-intensity profiles observed. The interplanetary shock may either reduce or enhance the particle intensity observed at a specific point in space and the observed effects are very dependent on energy.

Tooth Color as a Predictor of Oral Health-Related Quality of Life in Young Adults. Smiling plays an important role in social interaction. The purpose of this research was to explore the extent to which objective parameters of color of one's own teeth affected the social and emotional dimensions of young adults' lives. The sample included 134 subjects-students of the University of Rijeka, Croatia (65% female) aged 19 to 28 years (median 21). All subjects had six intact maxillary anterior teeth without restorations or severe malocclusions and healthy gingiva with no signs of inflammation. Tooth color was assessed intraorally using a spectrophotometer. Lightness, chroma, and translucency of the right maxillary central incisors (the reference teeth) were calculated and used for analysis. Subjects reported dimensions of their oral health-related quality of life (OHRQoL) using the Oral Health Impact Profile (OHIP), Orofacial Esthetic Scale (OES), and the Psychosocial Impact of Dental Aesthetics Questionnaire (PIDAQ). Linear relationships between elements of tooth color and OHRQoL were explored using Pearson correlations. Multiple linear regression, while controlling for the influence of age and gender, was also calculated. ANOVA with a Tukey post hoc test was employed to test whether nonlinear relationships existed between OHRQoL and categories of color elements. Dental self-confidence, esthetic concerns, orofacial appearance, social impact and psychological impact were not related to lightness, chroma, or translucency of the subjects' teeth. Neither linear nor nonlinear relationships were detected between those aspects. Satisfaction with smile esthetics was only related to translucency where subjects with moderate translucency were least likely to be satisfied (p = 0.033). Women tended to report greater psychosocial impacts than men (p < 0.05), regardless of their tooth color. According to the results of this study objective, measurable, quantitative parameters of tooth color did not accurately predict psychosocial dimensions of OHRQoL in dentate young adults.

Comparison of muscle-sparing thoracotomy and thoracoscopic ligation for the treatment of patent ductus arteriosus. We reviewed our experience with the treatment of patent ductus arteriosus (PDA), and compared two therapeutic techniques; muscle-sparing thoracotomy (MST) and thoracoscopic PDA ligation (TPDAL). We reviewed the clinical records and operative reports of 19 nonnewborn patients who were treated at our institution for PDA. Eleven patients underwent TPDAL and eight patients MST. The TPDAL patients underwent thoracoscopic clipping (ligation) of the PDA, whereas the MST group had a complete division of the ductus. A two-tailed Student's t test was used to calculate the 95% confidence intervals for length of operation, number of doses of intravenous narcotics and hospital stay. Costs were also compared. All patients underwent diagnostic echocardiography in the evaluation of an asymptomatic murmur. Both groups were similar in age (average, 4 years) and gender. All procedures were performed electively. Two thoracoscopic attempts were aborted, one for bleeding and the other for inadequate clip size. The length of the procedure averaged 1.3 hours +/- 0.330 SD for TPDAL versus 1.4 hours +/- 0.335 SD for MST. Five of the nine successful TPDAL patients were admitted to the Pediatric Intensive Care Unit (PICU) with an average length of stay of 20 hours, and two of eight MST patients stayed in the PICU for average of 18 hours. All patients were extubated after the procedure. Chest tubes were placed in two TPDAL patients and three MST patients. However, two patients who underwent TPDAL required tube thoracostomy for persistent postoperative pneumothorax. Average number of intravenous narcotics administered for the TPDAL was 1.2 doses per patient and for MST, 1.75 doses per patient. Mean hospital stay for TPDAL was 1.33 +/- 0.71 SD days and for MST 1.8 +/- 0.83 SD days. Ninety-five percent (95%) confidence intervals for the difference in means demonstrated no difference between the two groups for length of operation, hospital stay, or number of doses of intravenous narcotics administered. The authors were unable to identify any benefit to thoracoscopic patent ductus arteriosus ligation versus muscle-sparing thoracotomy in terms of hospital stay, length of operation, or morbidity. Additionally, with MST there is a complete division of the PDA theoretically decreasing the risk of recurrence in comparison with clip ligation.

[Experimental study of miRNA200a regulating Wnt/β-catenin signaling pathway in silica-induced mouse lung epithelial cells]. Objective: To observe the effect of overexpression of miRNA200a (miR-200a) recombinant lentivirus on the expression of Wnt/β-catenin signaling pathway in mouse lung epithelial cell line MLE-12 induced by silica (SiO(2)) . Methods: The mice were divided into SiO(2) control group (SiO(2)) , virus control group (SiO(2)+Lv-NC) group and overexpressing miR-200a virus group (SiO(2)+Lv-miR-200a). The expression of β-catenin, MMP2, MMP9, TCF-4 and Cyclin D1 mRNA and protein were detected by realtime-PCR and western blot after incubating cells for 18 h stimulating at the final concentration of 200 μg/ml of SiO(2). Results: The expression of miR-200a in MLE-12 cells of SiO(2)+Lv-miR-200 a group was significantly higher than that in SiO(2) group and SiO(2)+Lv-NC group. The mRNA and protein expression of β-catenin, MMP2, MMP9, TCF-4 and Cyclin D1 in MLE-12 cells of SiO(2)+Lv-miR-200a group were significantly lower than those in SiO(2) group and SiO(2)+Lv-NC group (P<0.05) . Conclusion: Overexpression of miR-200a can inhibit the expression of related genes of Wnt/β-catenin signaling pathway in silica-induced mouse lung epithelial cells.

Amplification of "defective" retrotransposon gtwin in D. melanogaster strain carrying large complex chromosomal aberration. Transposable elements (TE) are found in all eukaryotic genomes and play a significant role in their structure and functioning. The majority of mobile elements are silent in the genomes indicating the existence of cell control mechanisms of their activity. Establishment of immunity to TE is of great interest, but it cannot be studied directly and there are only few examples of present or recent active transpositions of mobile elements. G32, a Drosophila melanogaster strain, is characterized by the presence of large complex chromosomal aberration in the 3rd chromosome, active transpositions of gtwin in the past, and its stability at present. To address the question as to what had happened to the element while the cell took it under the control, we performed the detailed cytological and molecular analyses of gtwin's structure and its distribution in G32. Two variants of gtwin were found, one of which is amplified in G32 despite the alteration of tRNA-primer binding site. This element is accumulated in the aberrant chromosome and associated with the inversions breakpoints. Gtwin copies are predominantly localized in euchromatic regions and at least three of them are situated in heterochromatin. One copy was found in the piRNA cluster that might have caused silencing of the element.

Identification and functional signature of genes regulated by structurally different ABL kinase inhibitors. Dasatinib is an ATP-competitive, multi-targeted SRC and ABL kinase inhibitor that can bind BCR-ABL in both the active and inactive conformations. From a clinical standpoint, dasatinib is particularly attractive because it has been shown to induce hematologic and cytogenetic responses in imatinib-resistant chronic myeloid leukemia patients. The fact because the combination of imatinib and dasatinib shows the additive/synergistic growth inhibition on wild-type p210 BCR-ABL-expressing cells, we reasoned that these ABL kinase inhibitors might induce the different molecular pathways. To address this question, we used DNA microarrays to identify genes whose transcription was altered by imatinib and dasatinib. K562 cells were cultured with imatinib or dasatinib for 16 h, and gene expression data were obtained from three independent microarray hybridizations. Almost all of the imatinib- and dasatinib-responsive genes appeared to be similarly increased or decreased in K562 cells; however, small subsets of genes were identified as selectively altered expression by either imatinib or dasatinib. The distinct genes that are selectively modulated by dasatinib are cyclin-dependent kinase 2 (CDK2) and CDK8, which had a maximal reduction of <5-fold in microarray screen. To assess the functional importance of dasatinib regulated genes, we used RNA interference to determine whether reduction of CDK2 and CDK8 affected the growth inhibition. K562 and TF-1BCR-ABL cells, pretreated with CDK2 or CDK8 small interfering RNA, showed additive growth inhibition with imatinib, but not with dasatinib. These findings demonstrate that the additive/synergistic growth inhibition by imatinib and dasatinib may be mediated in part by CDK2 and CDK8.

[Effect of written patient information on knowledge and function of patients with acute uncomplicated back pain (PIK Study)]. If patients return early in the course of acute, uncomplicated back pain to their normal activities, their symptoms improve more quickly. Written detailed patient information can have a positive effect on knowledge and can increase physical activity. In this study the effect of a short evidence-based back pain leaflet on knowledge, function and patients' beliefs was investigated. A randomised controlled trial was carried out in 12 primary care practices. Patients with acute, uncomplicated back pain received either the back-pain specific information (intervention) or a leaflet without content regarding back pain (control). Participants' data were inquired before consultation of the general practitioner, as well as 1 week and 3 months later. Outcome measures were SF-36, FABQ-D, FFbH-R, knowledge concerning back pain, frequency of use of the leaflet, usefulness of the information and change of behaviour. The included patients totaled 174. The response rates were 74.7% (1 week) and 67% (3 months). Patients receiving the intervention leaflet showed better knowledge at 1 week and greater improvement in function scores at 3 months. There was no effect on patients' beliefs. Patients of the intervention group reported more activity in everyday life. Short written information may have small, in total possibly positive effects on knowledge, support of activity and function in patients with acute, uncomplicated back pain.

Grouping of residual solvents present in pharmaceuticals using experimental planning and chemometric methods. The main effects of six experimental factors on the efficiency of HS (headspace) extraction in headspace gas chromatography--flame ionization detector (HS-GC-FID) determination of twenty organic solvents routinely used in production of pharmaceuticals were obtained on the basis of the results of experiments carried out according to the Plackett-Burman factorial design. The effects were used as a basis for grouping the solvents into five groups, the solvents belonging to a group responded similarly to changes of HS conditions. To this end, visualization approaches were used as well as chemometric methods: cluster analysis (CA) and principal component analysis (PCA). Moreover, the most important HS experimental factors were selected for further optimization of the HS-GC determination procedure.

Management of the traumatized liver: an appraisal of 63 cases. A review of all patients with liver trauma admitted to the Royal Adelaide Hospital during the period 1983-86 was undertaken. Twelve of the 63 patients died. Liver trauma was responsible in eight (giving a mortality rate of 12.7%). The overall mortality rate was 19.0%. Most of the liver injuries (83%) were due to blunt trauma. All the deaths occurred in this group and were related directly or indirectly to blood loss. A high mortality (83%) was associated with hepatic vein injury. Right hepatectomy was unsuccessful in preventing death in any of these patients. The management of major venous injuries is discussed. A significant number of the liver injuries was minor. Analysis of these suggests that a more conservative approach to the management of haemodynamically stable patients might be appropriate.

Comparison of V[Combining Dot Above]O2peak Performance on a Motorized vs. a Nonmotorized Treadmill. Morgan, AL, Laurent, CM, and Fullenkamp, AM. Comparison of V[Combining Dot Above]O2peak performance on a motorized vs. a nonmotorized treadmill. J Strength Cond Res 30(7): 1898-1905, 2016-Despite growing popularity of nonmotorized treadmills (NMTs), little data exist regarding responses during exercise testing using this equipment, which is important when providing an appropriate exercise prescription. The purpose of this study was to evaluate physiological and perceptual responses during peak graded exercise tests (GXTs) on a motorized treadmill (MT) vs. NMT. Volunteers (12 men and 12 women aged 18-35 years) performed 2 peak GXT sessions (1 MT and 1 NMT). Respiratory gases and heart rate (HR) were collected each minute; perceptual response was estimated (Borg's 6-20 rating of perceived exertion [RPE] scale) during the final 10 seconds of each stage. Peak values (i.e., V[Combining Dot Above]O2, HR, speed) were determined during the final 10 seconds of each test; ventilatory threshold (VT) was assessed using the V-slope method. Paired t-tests matching variables measured at each stage of the GXT identified significantly higher values on the NMT for V[Combining Dot Above]O2 83% of the time, HR 67% of the time, and RPE 25% of the time. Interestingly though, neither peak V[Combining Dot Above]O2 (48.6 ± 9.2 ml·kg·min vs. 47.8 ± 8.9 ml·kg·min), peak HR (185 ± 9 b·min vs. 188 ± 10 b·min; p = 0.90), nor VT (72.7 ± 5.7% vs. 73.8 ± 5.4%) were significantly different on the NMT vs. the MT. However, significant differences were identified between NMT and MT tests for time to exhaustion (9:55 ± 1:49 vs. 12:05 ± 2:48; p < 0.01) and peak speed (8.0 ± 0.9 mph vs. 9.2 ± 1.4 mph; p < 0.01). Thus, although peak values obtained were similar between testing sessions on the NMT and MT, the majority of submaximal data were significantly different between trials. These differences are important when designing exercise prescriptions using submaximal values from NMT testing that may be inappropriately high or low at corresponding intensities during training.

Peptides of aminoxy acids as foldamers. This Feature Article summarizes our efforts in developing a new family of foldamers from alpha-, beta- and gamma-aminoxy acids. From a series of conformational studies, we demonstrate that peptides consisting of aminoxy acids adopt several well-defined secondary structures, such as alpha N-O turns (which feature an eight-membered-ring hydrogen bond), beta N-O turns (a nine-membered-ring hydrogen bond), gamma N-O turns (a ten-membered-ring hydrogen bond), 1.8(8) helices (consecutive homochiral alpha N-O turns), 7/8 helices (alternating alpha N-O turns and gamma-turns), 1.7(9) helices (consecutive beta N-O turns), reverse turns (consecutive heterochiral alpha N-O turns) and sheet-like structures.

Facial Performance Transfer via Deformable Models and Parametric Correspondence. The issue of transferring facial performance from one person's face to another's has been an area of interest for the movie industry and the computer graphics community for quite some time. In recent years, deformable face models, such as the Active Appearance Model (AAM), have made it possible to track and synthesize faces in real time. Not surprisingly, deformable face model-based approaches for facial performance transfer have gained tremendous interest in the computer vision and graphics community. In this paper, we focus on the problem of real-time facial performance transfer using the AAM framework. We propose a novel approach of learning the mapping between the parameters of two completely independent AAMs, using them to facilitate the facial performance transfer in a more realistic manner than previous approaches. The main advantage of modeling this parametric correspondence is that it allows a "meaningful" transfer of both the nonrigid shape and texture across faces irrespective of the speakers' gender, shape, and size of the faces, and illumination conditions. We explore linear and nonlinear methods for modeling the parametric correspondence between the AAMs and show that the sparse linear regression method performs the best. Moreover, we show the utility of the proposed framework for a cross-language facial performance transfer that is an area of interest for the movie dubbing industry.

Annual risk of tuberculous infection in rural areas of Junagadh district. Paucity of epidemiological data on tuberculosis in India prompted the National Tuberculosis Institute, Bangalore to embark upon a nation-wide survey to estimate the Annual Risk of Tuberculosis Infection in different parts of the country. The survey in Junagadh district, one of the 26 districts drafted under the nation-wide survey is reported here. The prevalence of infection from the analysis of 3164 children not displaying scars of the BCG vaccination was 4.16% (CI: 3.17-5.14) and from this data the ARI was computed as 0.73% (CI: 0.55-0.91). The inclusion of vaccinated children into the study group yielded similar results. The estimate of the ARI in Junagadh district is lesser than that in several other parts of India which is probably in consonance with its better socio-economic development.

A partial-propensity formulation of the stochastic simulation algorithm for chemical reaction networks with delays. Several real-world systems, such as gene expression networks in biological cells, contain coupled chemical reactions with a time delay between reaction initiation and completion. The non-Markovian kinetics of such reaction networks can be exactly simulated using the delay stochastic simulation algorithm (dSSA). The computational cost of dSSA scales with the total number of reactions in the network. We reduce this cost to scale at most with the smaller number of species by using the concept of partial reaction propensities. The resulting delay partial-propensity direct method (dPDM) is an exact dSSA formulation for well-stirred systems of coupled chemical reactions with delays. We detail dPDM and present a theoretical analysis of its computational cost. Furthermore, we demonstrate the implications of the theoretical cost analysis in two prototypical benchmark applications. The dPDM formulation is shown to be particularly efficient for strongly coupled reaction networks, where the number of reactions is much larger than the number of species.

Length of stay and long-term mortality following ST elevation myocardial infarction. Over the last few decades, there has been a significant reduction in hospital length of stay (LOS) among patients undergoing percutaneous intervention (PCI) for ST elevation myocardial infarction (STEMI). Although studies have looked at predictors of long hospital stay after STEMI, the impact of LOS on long-term outcomes after PCI remains unknown. We aimed to evaluate the association between LOS at the time of index hospitalization for PCI and long-term mortality among patients presenting with STEMI. We examined all patients undergoing PCI for STEMI at the Cleveland Clinic Catheterization Laboratory between 2002 and 2011. Long-term all-cause mortality was assessed using the Social Security Death Index and electronic medical record review. LOS was extracted from the discharge summary of the index hospitalization. A total of 1,963 patients were included in the study. Of these 1,963 patients undergoing PCI for STEMI, 126 (6.4%) died during the index hospitalization. Among survivors of this hospitalization, we observed a significant increase in long-term mortality with an increase in LOS during index hospitalization (P < 0.001). Adjustment for demographic and clinical characteristics yielded statistically significant increased mortality among patients with LOS of 6-10 days [HR (95% CI): 2.2 (1.3-3.5)] and LOS > 10 days [HR (95% CI): 2.6 (1.6-4.3)], in comparison with patients with LOS of 1-2 days. Long hospital stay after PCI among patients with STEMI was associated with an increased long-term mortality. A long hospital stay may be used as a marker to identify patients at higher risk for long-term mortality.

[CT-angiography in planning stereotaxic biopsies]. Twenty-one patients referred for stereotactic biopsy were studied by CT angiography. Helical CT with 1 mm collimation was obtained (pitch of 1:1). Multiplanar reconstructions were performed; maximum intensity projections and shaded-surface displays were generated by connectivity-based editing tools. The visualization of cerebral vessels was excellent. No further conventional angiography was needed. Improved information was obtained about localization of the intracranial lesion and its relationship to neighboring vessels. No bleeding complications were detected by CT after stereotactic biopsy.

Latent cerebral artery stenoses on magnetic resonance angiography in a patient diagnosed as probable Alzheimer disease. A 65-year-old woman with hypertension developed slowly progressive memory disturbance and disorientation. She was diagnosed as having Alzheimer-type dementia according to clinical criteria. Later her cognitive deterioration was noted to fluctuate in parallel to her blood pressure. Magnetic resonance angiography and single photon emission computed tomography showed bilateral middle cerebral artery stenoses and middle cerebral artery watershed dominant hypoperfusion. It is postulated that the patient's cognitive disturbance may have originated from vascular lesions.

Noncontact rack-pinion-rack device as a differential vibration sensor. We study a nanoscale system composed of one corrugated cylinder (pinion) placed between two corrugated plates (racks). The pinion and racks have no mechanical contact, but are coupled via the lateral Casimir force-one of the most spectacular consequences of quantum fluctuations of the electromagnetic field. The noncontact design of the device could help with the noteworthy wear problem in nanoscale mechanical systems. We consider the case where both racks undergo harmonic lateral motion. We assume that the amplitude, frequency, and phase of one of the racks are known. We show that probing the pinion motion, one can determine the vibration characteristics of the other rack.

Adult vaccination, part 2: vaccines for persons at high risk. Teaching Immunization for Medical Education (TIME) Project. The morbidity and mortality from vaccine-preventable diseases are high among adults with underlying medical conditions. Influenza vaccination is recommended annually, optimally between October and mid-November, for all persons 50 years of age and older and those with cardiac disease with potential for altered hemodynamics, diabetes mellitus, immunocompromising conditions, pulmonary disease, or renal disease. This season, because of production delays, influenza vaccination campaigns are planned for November. Pneumococcal polysaccharide vaccination is recommended for all persons 65 years and older and for those with alcoholism, asplenia, cardiac disease, cirrhosis, diabetes mellitus, immunocompromising conditions, pulmonary disease, or chronic renal disease. Indications for hepatitis B vaccination include chronic renal disease and hemodialysis, as well as employment in health care or employment as a mortician or public safety officer. It is also recommended for homosexual men, those who have multiple sex partners or a sexually transmitted disease, and injection drug users.

The impact of practice guidelines and funding policies on the use of new drugs in advanced non-small cell lung cancer. Cancer Care Ontario's (CCO) Program in Evidence-based Care has provided a credible basis for policy development and the funding of new and expensive anticancer drugs in the province of Ontario. In November 1997, vinorelbine was approved for the first-line treatment of advanced non-small cell lung cancer (NSCLC) on the basis of evidence-based practice guidelines generated by the Provincial Lung Disease Site Group. In June 1998, gemcitabine was approved as an alternative to vinorelbine for use in selected patients (e.g. significant venous access problems, peripheral neuropathy, severe toxicity to vinorelbine). A provincial drug database was used to determine the impact that these new policies had on the rate of vinorelbine and gemcitabine uptake within the CCO new drug funding programme. Drug utilization data for vinorelbine and gemcitabine from October 1997 to June 1999 were obtained from the CCO drug database. Individual patient data consisted of age, gender, first-line agent used, number of treatments, duration of therapy, treatment location (regional cancer centre vs. other) and total cost. Demographic and drug utilization data were analysed descriptively as means, medians, or proportions. Multivariable logistic regression analysis was then used to identify factors associated with the selection of gemcitabine over vinorelbine, as a first-line therapy. Following the approval of the first policy in November 1997, there was a rapid adoption of vinorelbine use in new NSCLC patients. When the gemcitabine policy was approved in June 1998, there was a rapid uptake in its use reaching a stable plateau of approximately 15% of all NSCLC patients within 9 months. The logistic regression analysis identified patient age greater than 65 years [odds ratio (OR) = 1.90, P = 0.001] and treatment in a non-regional cancer setting (OR = 1.71, P = 0.008) as significant predictors of gemcitabine utilization. Overall, the mean drug cost per patient treated with first-line gemcitabine was significantly higher than vinorelbine (Can 2590 dollars vs. Can 1030 dollars, P < 0.001). The new funding policies were associated with a rapid increase in drug utilization reaching a stable plateau within 9 months. Factors contributing to the usage of these new drugs for NSCLC included patient characteristics, such as age and treatment location.

Rheological properties of phosphorylated exopolysaccharide produced by Sporidiobolus pararoseus JD-2. The exopolysaccharide (EPS) produced by Sporidiobolus pararoseus JD-2 contained about 2.0% phosphorus and its zeta potential was -30mV at pH 6.0. This indicated that it was an anionic polymer. In steady shear measurements, there was a Newtonian plateau in low shear rates, but power-law behavior exhibited at high shear rates. So Williamson model was used to study the flow character of the EPS solutions. This phenomenon was according to its high molecular weight and entanglement networks. Considering the EPS was an anionic polymer, the influence of added salts on apparent viscosity of EPS were studied. Different NaCl concentrations had little effect on the viscosity of the EPS, but high concentrations of CaCl2 increased the viscosity of EPS significantly. EPS solutions showed inapparent thixotropic properties in stress growth and thixotropic loop experiment. According to the flow curve results and oscillatory shear results obtained, the rheological properties of EPS solutions were closer to that of entanglement network system, like carboxy methyl cellulose rather than weak gel structure such as xanthan gum. The EPS had the function to enhance immunological functions. Understanding the rheological characteristics of EPS was essential to exploit the functionality of this EPS in different food or medicine systems.

[Stop smoking help: a need]. Today the smoker carries a risk of mortality 70% higher compared to the nonsmoker. In Belgium active smoking is indisputably the most important cause of avoidable death. In 2004 it appears that 27% of the belgian population was smoking. This review describes the comorbidity associated with active tobacco consumption and defines the concepts of dependence and smoking cessation. It also identifies the three factors which determine the success of smoking cessation, i.e. the degree of nicotinic dependence, the presence of anxio-depressive disorders and the importance of the motivation to the stop.

Conservative Treatment with Octreotide to Provide Early Recovery of Children with Esophageal Perforation. The effectiveness of nonoperative treatment of esophageal perforation (EP) in children with octreotide is highlighted. Records of nine patients (seven boys and two girls with an average age of 5.83 ± 5.35 years) with EP were reviewed. EP developed in six patients during dilation of esophageal stenosis (five of six caused by caustic burns). In the other three patients, EP developed after nasogastric placement, after endotracheal intubation, and during endoscopy for foreign body. The symptoms consisted of dyspnea in four patients, tachypnea in seven patients, fever in six patients, chest pain in two patients, and abdominal pain in one patient. Two patients had pneumomediastinum, four patients had pleural effusion, one patient had subcutaneous emphysema, four patients had pneumothorax, and two patients had severe sepsis. Eight of the perforations resolved spontaneously. Therapy included cessation of oral feedings, implementation of proper antibiosis, parenteral and/or enteral nutrition by gastrostomy, and drainage of pleural effusions or mediastinal abscesses if required. Though not recommended by literature, octreotide was administered to these patients. Only one patient was operated in another clinic and was lost during follow-up. The length of hospitalization stay had a median of 11 ± 6.59 days, ranging between 5 and 28 days. If the patient who was operated and did not receive octreotide therapy is excluded, the median hospitalization was only 8 days (5 to 12 days). All patients in our series (except patient 8) survived and still have their native esophagus. The initiation of octreotide treatment in the early period after diagnosis of EP without surgical intervention leads to early improvement in children.

Differential modulation of the glutamate transporters GLT1, GLAST and EAAC1 by docosahexaenoic acid. At present, the ability of polyunsaturated fatty acids (PUFAs) to regulate individual glutamate transporter subtypes is poorly understood and very little information exists on the mechanism(s) by which PUFAs achieve their effects on the transport process. Here we investigate the effect of cis-4,7,10,13,16,19-docosahexaenoic acid (DHA) on the activity of the mammalian glutamate transporter subtypes, GLT1, GLAST and EAAC1 individually expressed in human embryonic kidney (HEK) cells. Exposure of cells to 100 muM DHA increased the rate of d-[(3)H]aspartate uptake by over 72% of control in HEK(GLT1) cells, and by 45% of control in HEK(EAAC1) cells. In contrast, exposure of HEK(GLAST) cells to 200 muM DHA resulted in almost 40% inhibition of d-[(3)H]aspartate transport. Removal of extracellular calcium increased the inhibitory potential of DHA in HEK(GLAST) cells. In contrast, in the absence of extracellular calcium, the stimulatory effect of DHA on d-[(3)H]aspartate uptake in HEK(GLT1) and HEK(EAAC1) cells was abolished, and significant inhibition of the transport process by DHA was observed. Inhibition of CaM kinase II or PKC had no effect on the ability of DHA to inhibit transport into HEK(GLAST) cells but abolished the stimulatory effect of DHA on d-[(3)H]aspartate transport into HEK(GLT1) and HEK(EAAC1) cells. Inhibition of PKA had no effect on the modulation of d-[(3)H]aspartate transport by DHA in any of the cell lines. We conclude that DHA differentially modulates the GLT1, GLAST and EAAC1 glutamate transporter subtypes via different mechanisms. In the case of GLT1 and EAAC1, DHA appears to stimulate d-[(3)H]aspartate uptake via a mechanism requiring extracellular calcium and involving CaM kinase II and PKC, but not PKA. In contrast, the inhibitory effect of DHA on GLAST does not require extracellular calcium and does not involve CaM kinase II, PKC or PKA.

Crown retention for non-retentive preparations using adhesive resin cements. This study examines the effect of preparing teeth with six varying convergence angles (ranging between 12 and 120 degrees) and height (1 and 2 mm) on the retention of cast gold crowns. Six groups of 4 human premolar teeth were prepared to give a flat occlusal surface in dentine with very short axial wall heights (1 or 2 mm) and variation in axial wall convergence (between 12 and 120 degrees). Impressions were recorded of the prepared teeth and custom castings made using a high copper content precious metal alloy. The castings were luted with an adhesive resin and stored in water at 37 degrees C for 24 hours prior to determining the pull-off force in an Instron Universal testing Machine at a cross head speed of 1mm min(-1). Twenty two of the twenty four tested specimens failed within the dentine of the tooth, irrespective of preparation orientation. Statistical testing using ANOVA demonstrated that there were no differences between the bond strength values for any of the preparation convergence angles or between preparations with 1 and 2 mm axial wall heights. This suggests that attachment strength of adhesively bonded castings with minimal axial wall height preparations is not influenced by the convergence angle of the preparation. The attachment strength exceeded that cohesive strength of the underlying dentine in nearly all of the adhesively luted restorations.

Atherosclerosis precursors in schoolchildren--results of a two-year intervention study. In order to reduce precursors of atherosclerosis, an intervention trial was carried out in pupils aged 10-11 years at the time of inclusion into the study (5th graders). The main goal of the study was to encourage health-promoting behaviour patterns--mostly present in the schoolchildren at that time--such as non-smoking, a negative attitude toward future smoking, a high level of physical activity including sports. The study design included dietary measures aimed at lowering blood pressure and total cholesterol values. Follow-up examination, performed at an interval of 2 years, revealed the following results: significantly lower mean total cholesterol values in girls attending the intervention schools; a significantly lower prevalence of smoking and a decrease in the number of casual smokers--compared with data obtained in the 5th grade--in the intervention schools; a negative attitude towards smoking and the extent of sport activities remained at the level of the 5th grade in the intervention schools.

Traction injury during minimally invasive harvesting of the saphenous vein is associated with impaired endothelial function. Many methods of minimally invasive surgical harvesting of the great saphenous vein have been developed because of the morbidity related to the long skin incision after traditional (open) great saphenous vein harvesting. One such method involves the use of multiple small incisions separated by 10- to 15-cm skin bridges through which the saphenous vein is harvested. We hypothesized that this method of saphenous vein harvesting might subject the saphenous vein to considerable traction forces, resulting in impaired endothelial cell function. Four-millimeter great saphenous vein segments were obtained from patients undergoing elective coronary artery bypass graft surgery. Group A (minimally invasive surgery) consisted of 23 rings from 20 patients (age, 65.8 +/- 11.1 years, mean +/- SD). Group B (open harvesting) consisted of 33 rings from 8 patients (age, 69.8 +/- 8.6 years). All great saphenous vein segments were undistended and were used within 24 hours of harvesting. Isometric tension experiments were performed on each ring of the great saphenous vein by using a force-displacement transducer to measure the force of contraction in grams. Measurements included developed force after exposure to high-potassium depolarizing solution and 50 micromol/L phenylephrine and decrease in force of contraction (relaxation) after exposure to 1 and 10 micromol/L acetylcholine. There were no differences between the minimally invasive surgery and open harvesting groups in their responses to high-potassium depolarizing solution or phenylephrine: high-potassium depolarizing solution, contractions of 4.26 +/- 0.72 g (mean +/- SEM) and 3.95 +/- 0.38 g, respectively (P =.70); phenylephrine, contractions of 3.49 +/- 0.63 g and 2.73 +/- 0.39 g, respectively (P =.41). There was no net relaxation in segments from the minimally invasive surgery group after exposure to 1.0 or 10 micromol/L acetylcholine. In contrast, rings from the open harvesting group demonstrated relaxation of -0.41 +/- 0.07 g and -0.32 +/- 0.09 g after exposure to 1.0 and 10 micromol/L acetylcholine, respectively. In undistended saphenous vein segments isolated from patients undergoing minimally invasive surgical and open techniques of harvesting, there was no acetylcholine-mediated endothelium-dependent relaxation in the minimally invasive surgery group. Therefore harvesting of the great saphenous vein through multiple small incisions might result in endothelial dysfunction, possibly caused by traction injury.

The effect of material hardship on child protective service involvement. This study employs four waves of survey data on 1,135 families from the Illinois Families Study, a longitudinal panel study of Temporary Assistance for Needy Families in Illinois. This study explores the following issues within this low-income population: (1) whether material hardships are associated with child protective services (CPS) investigations, (2) whether the effect of material hardship on CPS differs by the type of child maltreatment investigated, and (3) whether psychological distress mediates the association between material hardship and CPS involvement. Results from pooled and fixed effects logistic regressions suggest that caregivers who experience material hardship are more likely to become involved in CPS. In general, investigated neglect reports are responsive to particular types of hardship such as housing and food, while investigated physical abuse reports are responsive to levels of hardship regardless of specific types. The association between material hardship and CPS involvement is not fully explained by depressive symptoms or parenting stress. The study results suggest that in order to prevent child maltreatment, it may be necessary to address a family's unmet material needs through economic support interventions.

Risk differences between children and adults in road traffic injuries: a descriptive study from a tertiary-care hospital in a low-income country. Our study attempted to describe the differences in circumstances, risk groups, and severity of road traffic injuries (RTIs) among injured children (1-15 years) and adults (≥16 years) coming to the tertiary-care hospital, Karachi, Pakistan. Past medical records from June 2006 to May 2007 of injured patients coming to the Emergency Department of the Aga Khan University Hospital, Karachi were reviewed. Data were recorded regarding the basic epidemiological features, hospital stay, body parts that are injured, and severity of injuries. Of 411 RTI patients, males outnumbered females by a ratio of 4 : 1 accounting for 81% (n = 333) of injured. Among pedestrians (82; 20%), females were injured more than males (38 vs. 16%; P < 0.01). When compared with adults, injured children were mostly pedestrians (18 vs. 36%; P = 0.01) and presented with severe Glasgow Coma Scale (GCS) (9 vs. 18%; P = 0.02). Among adults, most RTIs were caused by two wheelers crashing with four wheelers (16 vs. 19%; P = 0.01). Motor vehicle occupants (adjusted odds ratio: 3.04; 95% confidence interval: 1.382-6.668) were more likely to have severe GCS (GCS < 8) even after adjusting for injury severity. The study may assist local authorities in Karachi to prioritize interventions to address common injuries among those who are at a high risk for RTIs. Further quantitative and qualitative studies are needed to assess the factors leading to RTIs among pedestrians in Karachi.