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Factors Affecting the Quality of Anticoagulation With Vitamin K Antagonists in Venous Thromboembolism Patients. Treatment of venous thromboembolism (VTE) is classically based on oral vitamin K antagonists (VKAs). Due to the disadvantages and side effects of these drugs, monitoring the quality of anticoagulation by assessing time within therapeutic range (TTR) is recommended. Variables altering the TTR in patients with VTE are yet to be determined. The aim of this study was to analyze the quality of anticoagulation in patients with VTE treated with VKAs and to identify factors associated with poor-quality anticoagulation. A retrospective observational study was performed in a cohort of 94 patients diagnosed with VTE undergoing treatment with VKAs. The TTR at 6 months was analyzed by the Rosendaal method. Univariate and a multivariate logistic regression analyses were performed to unravel factors that increase risk of poor-quality anticoagulation. The TTR at 6 months in this cohort was 60.5%; 54 patients had a TTR < 65%. In the univariate analysis, female sex, age ≥ 65 years, and renal impairment were significantly associated with poor-quality anticoagulation. However, in the multivariate logistic regression model, only renal impairment was independently associated with poor-quality anticoagulation (odds ratio = 3.31, 95% confidence interval [1.049, 10.486], p = .041). The average quality of anticoagulation was 60.5%, and a high percentage of patients had a quality of anticoagulation below recommended levels. Study findings indicate that renal impairment is an independent risk factor for poor-quality anticoagulation in patients with VTE treated with VKAs.

Total synthesis of both enantiomers of the macrocyclic lactone citreofuran. Both enantiomers of the polyketide-derived lactone citreofuran (4) have been prepared. The enantiopure building blocks were obtained on a chemoenzymatic route ((S)-6) and by a chiral pool synthesis ((R)-6). The crucial step in the synthesis, a macrolactonization, was accomplished under Mitsunobu conditions.

Molecular cloning and characterization of the guinea pig cholinephosphotransferase gene. Cholinephosphotransferase (CPT), the terminal enzyme in the de novo synthesis of phosphatidylcholine (PC), has an important role in regulating the acyl group of PC in mammalian cells. A 593bp cDNA coding for the 3(')-end of the CPT gene has been cloned from guinea pig liver using degenerative oligos based on the human CPT gene. It has 85% amino acid homology with the human CPT enzyme and amino acid variations were found to cluster at few points. Restriction enzyme polymorphisms were found particularly with respect to BamHI and NcoI. Hydrophobic and helix plot analysis of the sequence shows a similar pattern to human counterpart except for amino acid residues 142-179 and 173-179. PCR analysis suggested that a predominant pseudogene may be present in guinea pig and also the intronic sequences were much shorter when compared to the human CPT gene. We are the first to report on the C-terminal 195 amino acid residues of the CPT gene from any animal species alike in many aspects of cellular metabolism. The probable differences in genomic organization and its expression in different cancer cells have been discussed here having CPT as an important target for cancer drug development.

3-iodoanilinium 2-carboxy-6-nitrobenzoate: a three-dimensional framework built from O-H...O and N-H...O hydrogen bonds and a two-centre iodo-nitro interaction. In the title compound, C6H7IN+.C8H4NO6-, the anions are linked by a single type of O-H...O hydrogen bond into C(7) chains, and these chains are linked via three independent N-H...O hydrogen bonds into sheets. The sheets, in turn, are linked by a two-centre iodo-nitro interaction into a single three-dimensional framework.

Elevated serum YKL-40 level predicts myocardial reperfusion and in-hospital MACE in patients with STEMI. Macrophages in atherosclerotic plaques secrete YKL-40, a new biomarker of acute and chronic inflammation in patients with stable CAD. We hypothesized that YKL-40 may be a specific marker reflecting the burden of localized inflammation in myocardium and a predictor in patients with STEMI. In this study, we investigated the relationship of YKL-40 to in-hospital major adverse cardiac events (MACE), reperfusion parameters and its predictors in patients with STEMI. In total, 80 patients with STEMI and no history of prior coronary artery disease (CAD), who underwent primary percutaneous coronary intervention (p-PCI), were enrolled consecutively. In addition, 30 patients with normal coronary arteries (NCA) were enrolled as a control group. Cardiac biomarker levels including creatinine kinase-MB fraction (CK-MB), troponin-I, admission glucose and inflammatory markers including leukocytes and YKL-40 levels were measured as admission values. In our study, YKL-40 levels correlated to high-sensitivity CRP levels (r = 0.333, p = 0.003), TIMI risk score (r = 0.445, p < 0.001), age (r = 0.477, p < 0.001), pain to balloon time (r = 0.432, p < 0.001), leukocyte and neutrophil count (r = 0.386, p < 0.001 and r = 0.430, p < 0.001, respectively), hemoglobin (r = - 0.345, p = 0.002), admission and fasting blood glucose (r = 0.388, p < 0.001 and r = 0.427, p < 0.001), creatinine levels (r = 0.395, p < 0.001) and myocardial blush grade (r = - 0.334, p = 0.004). When the patients were divided into two groups determined by presence or absence of MACE, the patients with MACE had significantly higher levels of YKL-40 in comparison to the patients without MACE and the control group (194 ± 104, 114 ± 61 and 110 ± 53 μg/L, p < 0.001, respectively). In multivariate logistic regression analysis in STEMI patients, only YKL-40 level (OR: 1.011, 95%CI: 1.002-1.019, p = 0.011) and leukocyte count (OR: 1.264, 95%CI: 1.037-1.540, p = 0.020) were the independent predictors for MACE. Sensitivity and specificity of YKL-40 to predict MACE, when 125 μg/l was accepted as a cut-off value, were 84% and 70%, respectively. We found that serum YKL-40 is related to older age, increased admission glucose levels, leukocyte counts and decreased hemoglobin levels; YKL-40 level and leukocyte count independently predicted MACE.

Poisoning with dextropropoxyphene in Denmark. The sale of dextropropoxyphene is rising in Denmark, and the number of both fatal and non-fatal cases of poisoning with dextropropoxyphene is similarly rising. A total of 124 fatal and 297 non-fatal hospitalized cases of poisoning caused by dextropropoxyphene were reported to the National Board of Health in 1984. These figures are judged to be minimum figures. There is an accumulation of cases in the municipality of Copenhagen as compared to the remainder of the country. Cases of poisoning with dextropropoxyphene occur more frequently in socially and mentally encumbered groups. It is often difficult to determine with certainty the method of poisoning, but it is considered that the distribution is roughly one-third suicide or attempted suicide, about the same from accidental or simple over-dosage, while the remainder are uncertain. It is judged that the number of suicides or attempted suicides in normal persons is small, while the numbers in persons not entirely normal or carried out as an impulsive act are considerably higher. Other intoxicants, most frequently alcohol, have in more than one half of the cases been consumed together with dextropropoxyphene. The mortality rate for those cases reaching medical aid has been found to be 3.6% which is lower than the figure reported in other investigations. Very many of the cases of poisoning, however, are fatal at the time of discovery. Serious sequelae after non-fatal cases of poisoning are extremely rare. The steps being taken by the National Board of Health to reduce the number of cases of poisoning are mentioned, and the possibilities of reducing the number of cases are also discussed.

Beneficial role of insect-derived bioactive components against inflammation and its associated complications (colitis and arthritis) and cancer. Insect-based bioactive components are emerging as novel sources of drugs, effective against various diseases. Inflammation is considered to be an innate immune response developed by different organisms against foreign pathogens and cellular stress. However, repetitive elevated inflammation is considered to be responsible for development of many other diseases including colitis and arthritis. Due to the limited activities and side effects of non-steroidal anti-inflammatory drugs, researchers are continuously looking for alternative sources of drug molecules to alleviate the inflammatory related complications. Recently, insect-based bioactive components, such as venoms, haemocytes, cecropin A, papiliocin, N-acetyldopamine dimers, cecropin-TY1 peptide, cop A3 peptide, glycosaminoglycan, coprisin peptide, silk fibroin microparticles, and silk fibroin nanoparticles have been found to be active against different inflammatory mechanisms and associated diseases. Cancers, are some of the deadliest diseases, which are mainly treated by chemotherapy, radiation therapy and surgery. However, such treatments, mainly chemotherapy, is associated with enormous side effects. Therefore, as an alternative, less hazardous option, compounds from insects with anti-cancerous activity are being explored. Insect-derived compounds, such as cantharidin, norcantharidin, isocoumarin, plancyols A, plancypyrazine A, pancratistatin, narciclasine, and ungeremine, show potential anti-cancerous activity. In this review, we will be discussing the role of different potential drug molecules of insect origin with special emphasis on anti-inflammation and their association with health disorders and cancer.

The morphometric analysis of the V2 and V3 segments of the vertebral artery: normal values on MDCT. A potential hazard in midline posterior fossa craniectomy may be the injury of vertebral artery. That's why vertebral artery evaluation prior to surgery may prevent dangerous complications. Advancements in multidetector computed tomography (MDCT) have provided detailed demonstration of the vertebral artery at the craniocervical junction and its relationships with atlas and axis. We aimed to define the normal anatomic relationship of the V2 and V3 part of the vertebral artery on MDCT. In total, 33 patients underwent MDCT angiography scan with suspected cranial aneurysm. V2 and V3 segments of vertebral artery were evaluated. Eight measurements (B, C, D, E, G, H, X, and Y line) were taken from MDCT images. For B and C, a line initially passing through the body of axis and spinous process and determining the midline was formed. Then, the vertical distance of vertebral artery from the level of transverse foramen of axis and loop to this midline was measured. For D and G, the vertical distance of vertebral artery to the midline from the upper and lower margin levels of transverse foramen of atlas was measured after a line establishing the midline passing through the anterior and posterior tubercles of atlas was drawn first. For E, transverse diameter of vertebral artery was measured at the loop level of V2 segment. For H, the vertical distance at the point where vertebral artery entered dura in the line passing from the midline of foramen magnum at anterior-posterior plane was measured. For X and Y, two different points of horizontal part of the vertebral artery were determined. One of these two points was the lateral one which was the origin of the horizontal part in the transverse foramen, the other was the intersection point on atlas. Average distances for both sides from transverse foramen of the axis, the loop of axoatlantal part and the lower border of the atlas of the vertebral artery to the midline were 20.97 mm on the right, 22.29 mm on the left; 27.19 mm on the right, 28.34 mm on the left; and 25.75 mm on the right and 27.21 mm on the left, respectively. Average distances for both sides from the upper border of the atlas, and at its penetration through dura were 27.40 mm on the right, 28.94 mm on the left; and 10.90 mm on the right and 10.93 mm on the left, respectively. Distances between spinous process and intersection of vertebral artery with horizontal part were 35.79 mm on the right and 36.63 mm on the left laterally, and 22.27 mm on the right and 22.62 mm on the left medially. MDCT angiography is a powerful test to demonstrate the vasculature of the head and neck. Bony structures and adjacent vessel morphology can be evaluated by this technique. The evaluation of craniocervical region prior to surgery with MDCT may be helpful to avoid intraoperative vascular injuries.

A portable centrifugal analyser for liver function screening. Mortality rates of up to 50% have been reported after liver failure due to drug-induced hepatotoxicity and certain viral infections (Gao et al., 2008). These adverse conditions frequently affect HIV and tuberculosis patients on regular medication in resource-poor settings. Here, we report full integration of sample preparation with the read-out of a 5-parameter liver assay panel (LAP) on a portable, easy-to-use, fast and cost-efficient centrifugal microfluidic analysis system (CMAS). Our unique, dissolvable-film based centrifugo-pneumatic valving was employed to provide sample-to-answer fashion automation for plasma extraction (from finger-prick of blood), metering and aliquoting into separate reaction chambers for parallelized colorimetric quantification during rotation. The entire LAP completes in less than 20 min while using only a tenth the reagent volumes when compared with standard hospital laboratory tests. Accuracy of in-situ liver function screening was validated by 96 separate tests with an average coefficient of variance (CV) of 7.9% compared to benchtop and hospital lab tests. Unpaired two sample statistical t-tests were used to compare the means of CMAS and benchtop reader, on one hand; and CMAS and hospital tests on the other. The results demonstrate no statistical difference between the respective means with 94% and 92% certainty of equivalence, respectively. The portable platform thus saves significant time, labour and costs compared to established technologies, and therefore complies with typical restrictions on lab infrastructure, maintenance, operator skill and costs prevalent in many field clinics of the developing world. It has been successfully deployed to a centralised lab in Nigeria.

Positive affect, psychological well-being, and good sleep. To discover whether positive affect and purpose in life (eudaimonic well-being) are associated with good sleep independently of health problems and socioeconomic status, and to evaluate their role in mediating the influence of psychosocial risk factors on poor sleep. A cross-sectional study was carried out with 736 men and women aged 58-72 years, with positive affect assessed by aggregating ecological momentary samples. Sleep problems were assessed with the Jenkins Sleep Problems Scale, and psychosocial risk factors were measured by standardized questionnaires. Both positive affect and eudaimonic well-being were inversely associated with sleep problems after adjustment for age, gender, household income, and self-rated health (P<.001). Negative psychosocial factors including financial strain, social isolation, low emotional support, negative social interactions, and psychological distress were also related to reported sleep problems. The strength of these associations was reduced by 20-73% when positive affect and eudaimonic well-being were taken into account, suggesting that effects were partly mediated by positive psychological states. These results suggest that both positive affect and eudaimonic well-being are directly associated with good sleep and may buffer the impact of psychosocial risk factors. The relationships are likely to be bidirectional, with disturbed sleep engendering lower positive affect and reduced psychological well-being, and positive psychological states promoting better sleep.

Dental imaging. Radiography continues to be the initial test of choice in equine dental imaging for reasons of availability and ability to detect bone and tooth changes. Contrast radiography may be useful to characterize dental involvement in cases with draining tracts. For radiographically occult lesions, other modalities are useful. CT is better than plain radiography due to the inherent avoidance of superimposition of the opposite dental arcade, excellent bone density characterization, and good spatial resolution. Nuclear medicine may be useful to verify bone involvement in the dental region in cases in which the signs are particularly vague or not readily localized. Ultrasonography is an excellent test for soft tissue characterization and may assist with the characterization of suspected bone lysis, pathologic fractures, and abscesses.

Does mercury from amalgam restorations constitute a health hazard? Amalgam is the most extensively used implant material in dentistry. There have been no clinical trials of this substance and there are no epidemiological studies that allow any conclusions on the safety of amalgam fillings. Amalgam restorations continuously emit mercury vapour, which is absorbed in considerable quantities via the lungs. A comparison with dose-effect relationships, obtained in occupational studies, for certain effects on the kidneys and central nervous system (CNS), suggests that individuals with unusually high emission of mercury from amalgam fillings are at risk. It is unclear whether or not clinically significant effects could be expected. The limited sensitivity of available occupational studies, together with insufficient knowledge of possible host factors affecting resistance to mercury, implies that other more severe effects in susceptible individuals cannot be excluded. Information on long-term effects on organs other than brain or kidney is sparse. Animal studies suggest the possibility of immune system reactions to mercury, i.e. development of autoimmunity, that are not primarily dose-dependent, but rather depend on genetic susceptibility. From a toxicological point of view, amalgam is an unsuitable material for dental restorations.

[Modulit SL-20. Its development and clinical trial]. Modulit SZ-20 represents the third lithotriptor generation comprising the advantages of high disintegration efficacy, operation without anesthesia, combined system of ultrasonic and fluoroscopic localization of the concrements, provision with multifunctional platform. The impulse is generated by a cylindrical electromagnetic spiral with a paraboloid reflector. The waves go through a water cushion and impedance-adapted layer in which the patient is placed. Localization of the concrements is conducted by a special ultrasonic detector operating on-line, or fluoroscopically by an integrated arm C of the x-ray unit. In vitro and animal experiments have given evidence for high efficacy of the above lithotriptor, make it possible to evaluate dose-related and reversible renal trauma, to compare similar traumas induced by other lithotriptors. Since 1988 Modulit-SZ-20 has been tested for localization of nephroliths and ureteroliths. Then the attention of the designers was focused on concrement disintegration. After improving the X-ray guidance, the voltage of the generator, analysis of the experience gained, the percentage of disintegration has risen to 94. The authors achieved completed disappearance of the stones in 88% of their patients. SZ-20 Modulit proved effective against choleliths and stones in the biliary ducts as well. This device is recommended as high effective stone-crushing modality of the third generation.

A pilot study of transcatheter arterial interferon embolization for patients with hepatocellular carcinoma. Systemic, high-dose interferon-alpha treatment given three times per week subcutaneously induces tumor regression in approximately 30% of patients with inoperable hepatocellular carcinoma (HCC). The objective of the current study was to determine the efficacy and safety of transcatheter arterial interferon embolization for the treatment of patients with inoperable HCC. Eighteen patients with inoperable HCC were recruited to receive 3 different doses of interferon-alpha-2b (10 megaunits [MU]/m(2), 30 MU/m(2), or 50 MU/m(2)) at intervals of 8-12 weeks. Their tumor response, adverse events, and survival were monitored. In 14 patients with nondiffuse HCC, complete responses and partial responses (> 50% tumor reduction) were observed in 28.6% and 35.7% of patients, respectively. One of four patients with diffuse HCC had a partial response. Thirty-eight percent of patients had normalization of their alpha-fetoprotein level. The median ferritin level at the last follow-up was reduced significantly (765 pmol/L; range, 457-2720 pmol/L) compared with the baseline level (1980 pmol/L; range, 1100-3300 pmol/L; P = 0.011). The median survival was 15.9 months. Transient fever and rigor were the most common side effects observed. Five patients (27.8%) developed hypothyroidism. No significant liver decompensation was observed. This pilot study showed that transcatheter arterial interferon embolization was an effective method for the treatment of patients with inoperable HCC without significant hepatic toxicity.

Exploratory and confirmatory factor analysis of medical professionalism core attributes scale. Evaluating the professional attributes of medical students is critical, because medical professionalism is an essential quality of a good doctor. But, few studies have examined the tools for assessing such attributes. This study analyzed factors of medical professionalism in medical students to develop standards that can assess medical professional attributes. A total of 1,508 medical students in Korean medical schools or colleges answered a self-assessment survey of medical professionalism elements from 2005 to 2012 that we developed. The survey consisted of core 31 attributes on a 5-point Likert scale. Factor analysis was performed using SPSS version 20.0 and AMOS version 20.0. Exploratory factor analysis revealed six factors with total variance of 59.56%. The factors were termed 'empathy and accountability,' 'self-development skills,' 'academic competence,' 'interpersonal skills,' 'high intelligence,' and 'attitude towards oneself and life.' These factors showed statistically significant correlation (0.310~0.663). From the confirmatory factor analysis a six-factor model were appropriate (CFI=0.873, TLI=0.853, RMSEA=0.065). Cronbach-alpha of six factors ranged from 0.718 to 0.864. Good doctors need to have not only appropriate standards of medical knowledge but also skills to understand and communicate well with patients, as well as self-management skills, which should not be overlooked in the medical education curriculum. By optimizing the results of this study, a more refined assessment tool of professionalism can be exploited.

Sporogen, S14-95, and S-curvularin, three inhibitors of human inducible nitric-oxide synthase expression isolated from fungi. The induction of human inducible nitric-oxide synthase (iNOS) expression depends (among other factors) on activation of the signal transducer and activator of transcription 1 (STAT1) pathway. Therefore, the STAT1 pathway may be an appropriate target for the development of inhibitors of iNOS expression. HeLa S3 cells transiently transfected with a gamma-activated site (GAS)/interferon-stimulated response element-driven reporter gene construct were used as the primary screening system. Using this system, three novel inhibitors of interferon-gamma-dependent gene expression, namely, sporogen, S14-95, and S-curvularin, were isolated from different Penicillium species. These three compounds also inhibited cytokine-induced, GAS-dependent reporter gene expression in stably transfected human A549/8-pGASLuc cells, confirming the data obtained with the above-mentioned screening system. Furthermore, in A549/8 cells, sporogen, S14-95, and S-curvularin inhibited cytokine-induced activity of the human iNOS promoter [a 16-kilobase (kb) fragment in stably transfected A549/8-pNOS2(16)Luc cells], cytokine-induced iNOS mRNA expression, and cytokine-induced nitric oxide (NO) production in a concentration-dependent manner. The proliferation of A549/8 cells, and the activity of the human eNOS promoter (a 3.5-kb fragment in stably transfected ECV-pNOS III-Hu-3500-Luc cells), were only influenced marginally by the three compounds. Sporogen, S14-95, and S-curvularin also inhibited cytokine-induced activation of STAT1alpha in A549/8 cells. In conclusion, sporogen, S14-95, and S-curvularin represent new transcriptionally based inhibitors of iNOS-dependent NO production, acting on the Janus tyrosine kinase-STAT pathway. These compounds may represent lead structures for the development of drugs inhibiting iNOS-dependent overproduction of NO in pathophysiological situations.

Growth and characterization of pure and KCl doped zinc thiourea chloride (ZTC) single crystals. Potassium Chloride (KCl) as an additive is added into zinc thiourea chloride solution in a small amount (1M%) by the method of slow evaporation solution growth technique at room temperature to get a new crystal. Due to the doping of the impurities on the crystals, remarkable changes in the physical properties were obtained. The grown crystals have been subjected to different instrumentation methods. The incorporation of the amount of potassium and zinc in the crystal lattices has been determined by AAS method. The lattice dimensions have been identified from single crystal X-ray diffraction measurements. The presence of functional group for the grown crystals has been identified by FTIR analysis. The optical, thermal and mechanical behaviors have been assessed by UV-Vis, TG/DTA and Vickers hardness methods respectively. The presence of dislocations of atoms has been identified by etching studies.

Therapeutic advances in neurodegeneration with brain iron accumulation. Neurodegeneration with brain iron accumulation (NBIA) includes a heterogeneous group of genetically defined disorders characterized by progressive extrapyramidal deterioration and iron accumulation in the basal ganglia. Current medical options for these disorders remain largely unsatisfactory and do not prevent the disease from progressing to a severe and disabling state. In select cases, surgical techniques, such as deep brain stimulation, may be effective in ameliorating some of the symptoms of the disease. The availability of chelating agents with specific properties that have been demonstrated to be effective in other disorders with regional iron accumulation as well as magnetic resonance imaging techniques that allow for quantitative assessment of iron have stimulated interest in the use of chelating agents in NBIA. This review aims to describe the role of surgical therapies in NBIA, discuss the use of chelating agents in NBIA, and presents new therapeutic approaches under consideration.

Darapladib, a reversible lipoprotein-associated phospholipase A2 inhibitor, for the oral treatment of atherosclerosis and coronary artery disease. Darapladib, under development by GlaxoSmithKline plc, is a novel inhibitor of lipoprotein-associated phospholipase A2 (PLA2), an enzyme that may link lipid metabolism with inflammation, leading to the increased stability of atherosclerotic plaques present in the major arteries. Darapladib exhibits favorable pharmacokinetics, minimal predicted drug-drug interactions, sustained blood levels with once-daily oral dosing and limited inhibition of other PLA2 isozymes. Preclinical studies in diabetic-hypercholesterolemic swine (useful for the study of human atherosclerosis mechanisms) demonstrated that darapladib attenuated the progression of arterial plaques to a higher-risk phenotype by reducing the number of inflammatory macrophages within plaques and dampening T-cell responses. Two phase II clinical trials demonstrated sustained lipoprotein-associated PLA2 inhibition with daily oral dosing, and favorable effects on markers of inflammation and plaque stability. Phase III trials are ongoing to assess the safety and efficacy of darapladib in reducing adverse clinical events in patients with atherosclerosis.

Synthesis of organosoluble chitosan derivatives with polyphenolic side chains. A one-pot synthesis was used to produce chitosan derivatives with polyphenolic side chains via a regioselective phenolic coupling reaction. Under Mannich reaction conditions, treatment of chitosan with formaldehyde and methyl 2,4-dihydroxybenzoate gave N-(2,6-dihydroxy-3-methoxycarbonylphenyl)methylated chitosan in good yield (87%). Formation of a CC bond occurred regioselectively at the C(3) position of methyl 2,4-dihydroxybenzoate. Chitosan derivatives having various phenolic compounds as a side chain were easily synthesized in a similar manner. The chitosan derivatives showed good biodegradability and improved their solubility in methanol (9.8mg mL(-1)) and 2-methoxyethanol (> 10mg mL(-1)). The UV protection provided by the derivatives with phenolic benzophenone side chain was evaluated using UV spectra of polyethylene terephthalate and poly(vinyl butyral-co-vinyl alcohol-co-vinyl acetate) films coated with the derivatives and the derivatives absorbed effectively in the UV-A region (<60%). Self-aggregation of the chitosan derivatives with the phenolic side chain was observed by using a fluorescent probe in aqueous solution.

[Psychiatric disorders associated with high-dose methadone (>100 mg/d): a retrospective analysis of treated patients]. Recent studies show that high-dose methadone (>100 mg/d) allow a better control of the consumptions of illicit opiates by treated patients. The aim of this retrospective study was to analyze data of patients requiring high-dose methadone (>100 mg/d) as well as associated factors. We retrospectively reviewed charts of treated patients with high-dose methadone followed in the maintenance methadone treatment center between 01/01/07 and 01/07/10. The following variables (medical history, psychiatric comorbidities, associated drugs, and polyaddictions), were assessed with high-dose methadone, using an univariate and then a multavariate analysis. The threshold value of 130 mg/day (median of maximal daily dose) was used to perform analysis. During the study period, 78 patients, mainly men (75.6%), with a median age of 34 years [22-57] were included. The both groups with posology of methadone ≤ 130 mg/d (n=44) versus posology of methadone >130 mg/d (n=34) were close in term of demographic characteristics, consumption of drugs and associated treatments. Plasma methadone concentrations were higher in patients with the daily doses of methadone superior than 130 mg/d (NS), as well as the methadone metabolite (EDDP, p=0.048). Among studied factors, the presence of psychiatric comorbidities was significantly associated with high-dose methadone (threshold 130 mg/d) [OR 4,6 IC 95% (1.412;14.925)]. Seven patients presented with complications related to methadone: cardiac disorder (3), libido troubles (3) and hypofertility (1). Patients requiring high-dose methadone are polydrug addicts. In our study, patients with psychiatric comorbidities needed daily dose of methadone significantly more raised.

Home cage activity and behavioral performance in inbred and hybrid mice. Locomotor activity is a key component in many behavioral tests, suggesting that genetic differences in activity levels may be a critical consideration when comparing mouse strains. In order to assess the relationship between activity and performance, we recorded home cage activity, and locomotion and defecation, a non-activity-linked behavior, in tests of anxiety in inbred (C57BL/6J (B6), n = 25; BALB/cJ (C), n = 24; DBA/2J (D2), n = 28) and hybrid (CB6F1/6J (CB6: B6 x C) n = 19) mice. Under our test conditions, the strains showed significant differences in home cage activity levels: C > B6 > D2. The CB6 mice were similar to the B6 mice in horizontal activity and were intermediate between the parental strains in vertical movement. Based on measures of locomotion and defecation in the open field, emergence and novel object tests, and the elevated zero maze, the C mice appeared to be the most anxious and the B6 were the least anxious. The D2 mice were intermediate on some measures but more similar to B6 mice on others, making ranking them more difficult. In addition, the CB6 mice displayed characteristics of both parental strains. They had greater similarity to B6 mice in measures of horizontal movement in the home cage and locomotion in the open field and emergence tests, but exhibited defecation responses similar to those of C mice in the novel object test and elevated zero maze. The results suggest that strain differences in spontaneous locomotion should be considered when interpreting strain differences in behavioral tests, and that home cage activity may be a useful interpretive aid.

Delivering value to multiple stakeholders: 2013 and beyond. To deliver greater value, top payers and providers should: Measure the value they deliver to their business partners and customers, Create value through continuous performance improvement, Package and price value to optimize their margin, mission, and market share, Organize for value through new legal entities, employed medical groups, or both.

A novel and facile synthesis of carbon quantum dots via salep hydrothermal treatment as the silver nanoparticles support: Application to electroanalytical determination of H2O2 in fetal bovine serum. A simple, low-cost, and green process was used for the synthesis of carbon quantum dots (CQDs) through the hydrothermal treatment of salep as a novel bio-polymeric carbon source in presence of only pure water. The silver nanoparticles (AgNPs) were embedded on the surface of CQDs by ultra-violate (UV) irradiation to the CQDs and silver nitrate mixture solution. The as-synthesized CQDs and AgNPs decorated CQDs nanohybrid (AgNPs/CQDs) were characterized by UV-vis and photoluminescence spectroscopy, Fourier transform-infrared spectroscopy, transmission electron microscopy, atomic force microcopy, X-ray diffraction, and field emission scanning electron microscopy. Then, the AgNPs/CQDs nanohybrid was casted on the glassy carbon electrode in order to prepare an amperometric hydrogen peroxide (H2O2) sensor. The electrochemical investigations show that the AgNPs/CQDs nanohybrid possesses an excellent performance toward the H2O2 reduction. In the optimum condition, the linear range of H2O2 determination was achieved from 0.2 to 27.0μM with high sensitivity (1.5μA/µM) and the limit of detection was obtained about 80nM (S/N=3). Finally, the prepared nanohybrid modified electrode was effectively applied to the H2O2 detection in the disinfected fetal bovine serum samples, and the recovery was obtained about 98%. The achieved results indicate that the AgNPs/CQDs nanohybrid with high reproducibility, repeatability, and stability has a favorable capability in electrochemical sensors improvement.

[Chronic heart failure]. Incidence of chronic heart failure (HF) is increasing steadily in all developed countries, predominantly due to population ageing. The prevalence of HF in population is 1-2%, reaching up to 10% in higher age categories. At present HF is classified according to left ventricular ejection fraction (EF) value to HF with reduced EF (formerly systolic HF) and HF with preserved EF (formerly diastolic HF). Coronary artery disease dominates in the aetiology of HF with reduced EF (about 70%), especially status post myocardial infarction. Pathophysiology of HF with preserved EF is very complex and still not fully understood. Multiple comorbidities play an important role, especially hypertension and diabetes mellitus. HF with preserved EF represents about half of all HF cases and its rate is slowly increasing. Morbidity expressed as hospitalization rate is comparable in patients with both types of HF, whereas mortality is a little bit lower in patients with HF with preserved EF. But in patients with HF and preserved EF the prevailing causes of both, the hospitalizations and the deaths are non-cardiovascular.Diagnosis of HF is relatively simple in fully manifested cases, but it could be a problem in milder forms especially of the HF with preserved EF in elderly patients with multiple comorbidities. For the definite diagnosis of HF the patient has to have typical symptoms and clinical signs as well as objectively documented left ventricular dysfunction, usually by echocardiography. According to the EF value the type of HF is determined. In HF with preserved EF an evidence of a structural heart impairment and/or left ventricular diastolic dysfunction is also necessary. Plasma levels of natriuretic peptides could be helpful for determination of correct diagnosis, particularly in untreated patients. Basic examination of patients with suspected HF is completed by ECG and some laboratory parameters (e.g. renal function, ions, red blood count).Treatment of HF with reduced EF is based on evidence from many clinical trials. It is complex and consists on non-pharmacological interventions, pharmacotherapy (ACE inhibitors, sartans, betablockers, mineralocortikoid receptor blockers, in specific situations also ivabradine and digoxin), surgery and devices. There is no evidence-based treatment for HF with preserved EF, therefore it still remains empiric.

Strengthening the Child- and Youth-Serving Workforce: Surveying the Landscape, Overcoming Challenges. This special issue addresses a neglected but important topic in our field: strengthening the child- and youth-serving workforce. Investing in this workforce should be a national priority because considerable evidence has shown that investments in early childhood education and development, particularly in low-resource contexts, that are reinforced through skills-based programs in adolescence and adulthood, have beneficial impacts throughout life. Investing in quality child- and youth-serving programs also has the additional benefit of creating a productive and capable future workforce. The editors and authors of the special issue should be commended for producing the first special issue on this topic in our field or in related fields, one that is long overdue. Articles in this issue survey the landscape of an amorphous and complex area of practice and research and describe key challenges for the field. In this commentary, I offer organizing frameworks to characterize the child- and youth-serving workforce, note emerging issues when addressing specific challenges, and identify areas for future research.

Quality of the bottom sediment prior to dredging in the Golden Horn of Istanbul. The Golden Horn has experienced severe pollution due to uncontrolled domestic and industrial wastewater discharges until recent years. A restoration project has been developed by our universities, upon a request from Istanbul Metropolitan Municipality. Two principal alternatives for the dredging and disposal of the bottom sediments were considered: disposing on the land and disposing in the sea. Both of these alternatives include several sub-alternatives. Characterization of the sediment quality is crucially important for selecting the best alternative considering the cost, environmental impact and public acceptance. However, only a few and rather old studies were present with which it was not possible to get a comprehensive information on the critical sediment characteristics. Therefore, the aim of this study was determination of spatial distribution of sediment characteristics. The project area, at which the sediment quality determined, covers the part of the Golden Horn remaining at the upstream of Valide Sultan Bridge. The number of sampling stations were thirteen and the sediment samples were collected from 0.0m, 5.0m and 10.0m from the bottom surface. The following parameters were measured on each sample: Total solids, organic matter, total phosphorus, TKN, oil and grease, total sulphur, and sediment oxygen demand (SOD). Sediment oxygen demand parameter was further divided into three fractions, namely, biological (SOD-B) and chemical (SOD-C). Average organic content of the bottom sediment was around 10% while ammonia and sulfur exhibit very high levels. It is found that the bottom sediment is well stabilized with very low organic content below 5.0m from the bottom surface. It can be said that, removing the upper 5m of the bottom sediment will be enough for creating a relatively stable bottom surface which will cause oxygen depletion in the overlaying water at acceptable levels. High SOD values of the bottom sediment makes the alternatives considering disposal in the Marmara Sea and Black Sea inapplicable. High SOD-C values, especially, indicate that the sediment will cause a tremendous reduction in the oxygen concentration in a very short time at any marine environment, and even it may create anaerobic conditions. Therefore, disposal of dredged sediment into abandoned mines 4km from the Golden Horn by a pressure pipeline has been chosen as the best applicable alternative.

Inhibition of platelet function by hydroxyethyl starch solutions in chronic pain patients undergoing peridural anesthesia. The use of hydroxyethyl starch (HES) solutions as a fluid replacement before peridural blockade may compromise blood coagulation, thus increasing the risk of neuraxial bleeding. In this prospective, double-blind, placebo-controlled, crossover study, we compared the influence of HES 130 (molecular weight in kilodalton), HES 200, and lactated Ringer's solution on platelet function and hemodynamics in chronic low back pain patients scheduled for peridural blockades. Patients received 3 test infusions of 10 mL/kg each administered IV for 30 min. Collagen/epinephrine and collagen/adenosine diphosphate were used as agonists for assessment of platelet function analyzer-closure times. Arterial blood pressure, heart rate, platelet counts, and hemoglobin levels were documented. Platelet function analyzer-closure times remained stable after lactated Ringer's solution but were significantly prolonged after HES. The platelet-inhibiting effect of HES 200 was more than that of HES 130. Hemodynamic stability was sufficiently maintained by all test infusions. In contrast to previous observations, a relevant antiplatelet effect of both low and medium molecular weight HES solutions was found in this study in chronic pain patients undergoing peridural anesthesia. Because hemostasiological competence is a prerequisite for safe neuraxial blockade, the decision of HES for intravascular fluid administration before blockade should be critically made.

Bradykinin evoked depolarization of a novel neuroblastoma x DRG neurone hybrid cell line (ND7/23). Application of bradykinin (Bk) to neuroblastoma x dorsal root ganglion (DRG) neurone hybrid cells (ND7/23) evoked an inward (depolarizing) current associated with an increase in membrane conductance. This response was antagonized by D-Arg0,Hyp3,Thi5,8,D-Phe7-Bk, but was not mimicked by des-Arg9-Bk, indicating the involvement of B2-receptors. The response was unaltered by replacement of extracellular Na+ by N-methylglucamine. Replacement of extracellular Cl by gluconate shifted the estimate reversal potential to a more positive value, while the use of potassium acetate filled recording electrodes shifted the reversal potential to a more negative value, and reduced the response amplitude, indicating the importance of Cl- in the response. This response to Bk was mimicked by the calcium ionophore ionomycin. Bk stimulated the formation of inositol 1,4,5-trisphosphate (IP3), and increased the release of arachidonic acid. In addition, Bk produced an increase in [Ca2+]i, as determined by microspectrofluorimetry. This was due to the release of Ca2+ from intracellular stores, since the response was unaltered when the cells were bathed in Ca(2+)-free solution. In summary, Bk depolarizes ND7/23 cells, probably through the activation of a chloride conductance. It seems likely that this is secondary to the rise in cytosolic Ca2+ concentration, due to the release of Ca2+ from internal stores by IP3. This Ca(2+)-activated chloride response is present in some sensory neurones, although its role in the activation of sensory neurones by Bk is at present unclear.

Synthesis of TiO2 (B) and High-temperature Stable Anatase TiO2 Nanowires by Hydrothermal Method and Investigation of Photocatalytic Activity. In this study, TiO2 nanowires (TNWs) were synthesized through hydrothermal method and were characterized using X-Ray diffraction (XRD), transmission electron microscopy (TEM) and BET techniques. Monoclinic TiO2 (B) is the dominant phase of TNWs up to 600°C which is completely transformed into a highly crystalline anatase phase at 800°C. The photocatalytic activity of TNWs, prepared at various calcination temperatures, was investigated in the removal of Rhodamine B as an organic model pollutant. The results indicated that the photocatalytic activity of TNWs, prepared at 800°C calcination temperature, was better than that of other samples and even TiO2 -P25 nanoparticles.

Dysregulated mature IL-1β production in familial Mediterranean fever. The aim of this study was to analyse the role of circulating cleaved IL-1β in patients with FMF. We enrolled 20 patients with FMF (5 males and 15 females), 22 patients with RA (4 males and 18 females) and 22 healthy controls (6 males and 16 females). Serum levels of serum amyloid A (SAA) were measured by ELISA. We also determined whether IL-1β was present as the cleaved form (p17) in the sera of FMF patients by immunoblotting using anti-cleaved IL-1β antibody. Although SAA concentrations were elevated in the sera, there was no significant difference in these concentrations between FMF patients and RA patients. Immunoblot analysis demonstrated that the cleaved form of IL-1β (p17) was present in sera from FMF patients during febrile attack periods, but not in healthy controls. Bands representing the cleaved form of IL-1β were not detected in serum from FMF patients at non-febrile attack periods or remission periods under colchicine treatment. The amounts of cleaved IL-1β (p17) were significantly higher in patients with FMF compared with those in patients with RA in the inflammatory phase. The cleaved form of IL-1β is a valuable biomarker for monitoring disease activity and response to colchicine treatment in patients with FMF. It might be useful to discriminate FMF from other non-IL-1β-mediated inflammatory disorders.

[Blood coagulation changes in patients with post-splenectomy persistent thrombocytosis]. To clarify the possible role of persistent thrombocytosis after splenectomy as being a predisposing factor causing thromboembolism. Blood coagulation profiles were studied in 35 patients (20 M and 15 F, mean age 42 +/- 17.5) suffering from thrombocytosis (> 500,000/dl) who underwent splenectomy for non-malignant and non-traumatic diseases. Seventy healthy subjects acted as a control group. Tests were performed 6 months after the operation and for both groups (patients and controls) blood samples were collected for: platelets, fibrinogen, PT, APTT, AT III, plasminogen, F1 + 2, t-PA and DNA analysis for F V, F II and MTHFR. After one year all subjects were controlled for thrombocytosis, genomic abnormalities and venous thrombosis. All the analyses were performed according to the Statistical Package for Social Science. The significance of the differences in means was evaluated by non-parametric tests, differences with a P value < 0.05 being considered significant. Increased plasma levels of fibrinogen, D-dimer, F1 + 2 and PAI-1 were found in the patients compared with the control group. TPA was significantly lower in the patients than in the controls. At the one year follow-up, two patients with genetic polymorphism had suffered deep venous thrombosis. Our findings indicate that splenectomy contributes to abnormal platelet aggregation and endothelial cell activation with hypercoagulability.

Myeloid-derived suppressor cells are generated during retroviral transduction of murine bone marrow. Previous work by our group showed that transferring bone marrow cells transduced with an autoantigen into nonmyeloablated mice with experimental autoimmune encephalomyelitis induced immune tolerance and improved symptoms of the disease. Because this effect occurred in the absence of molecular chimerism, we hypothesized that the cells responsible did not have repopulating ability and that they were not mediating central but peripheral tolerance mechanisms. In the present study, we analyzed the immunophenotype of the cells that are generated in the transduction cultures and we evaluated the immunosuppressive activity of the main cell subpopulations produced. We show that both granulocytic (CD11b(+) Gr-1(hi)) and monocytic (CD11b(+) Gr-1(lo)) myeloid-derived suppressor cells (G- and M-MDSCs, respectively) are generated during standard 4-day γ-retroviral transduction cultures (representing about 25% and 40% of the total cell output, respectively) and that the effectively transduced cells largely consist of these two cell types. A third cell population representing about 15% of the transduced cells did not express CD45 or hematopoietic lineage markers and expressed mesenchymal stromal cell markers. Transduced total bone marrow cells and sorted M-MDSCs expressed arginase and inducible nitric oxide synthase activities, produced reactive oxygen species, and inhibited antigen-induced T-cell proliferation in vitro. Transgene-expressing MDSCs could be exploited therapeutically to induce tolerance in autoimmune diseases and in gene therapy protocols.

Activation of periaqueductal grey pools of beta-endorphin by analgetic electrical stimulation in freely moving rats. Electrical stimulation of the ventral midbrain periaqueductal grey (PAG) elicited an antinociception (analgesia) in freely moving rats. Stimulated animals displayed a pronounced decrease in levels of immunoreactive (ir)-beta-endorphin (beta-EP) in the midbrain PAG. This depletion was selective in that: animals placed in the chamber and not stimulated revealed neither an analgesia nor an alteration in levels of ir-beta-EP. No change in levels of ir-beta-EP was detectable in other brain regions. Both stimulated rats and rats placed in the chamber and not stimulated revealed a rise in circulating ir-beta-EP: the magnitude of this rise did not, however, differ between these groups. Levels of ir-Met-enkephalin, ir-Leu-enkephalin and ir-dynorphin A were modified neither in the PAG nor in other CNS tissues. The data demonstrate that electrical stimulation of the midbrain PAG selectively influences (presumably activates) pools of beta-EP therein. Together with our finding that destruction of PAG-localized beta-EP neurones to block stimulation-analgesia, the data suggest that an activation of intrinsic pools of beta-EP underlies stimulation-produced analgesia elicited from the PAG in the rat.

Differences in c-myc and pvt-1 amplification in SEWA sarcoma sublines selected for adherent or non-adherent growth. Conversion of solid sarcomas and carcinomas into ascites tumors depends on the in vivo selection of phenotypically altered tumor cell variants that can grow in the dissociated form. Once selected, they retain this property even after prolonged s.c. growth as solid tumors. From an s.c.-passaged subline of an ascites-converted murine sarcoma (SEWA-AS12), we were able to separate cells adapted to the ascites form of growth from cells that can only grow in the solid form on the basis of their differential adherence to plastic. Both c-myc and pvt-1 were amplified approximately 63- to 77-fold in the nonadherent subline (SEWA-AS12-NA), but only 5- to 8-fold in the adherent subline (SEWA-AS12-ADH). This suggests that c-myc and/or pvt-1 amplification may provide a selective advantage to cells that can grow in the dissociated form.

Efficacy of rapid-onset oral fentanyl formulations vs. oral morphine for cancer-related breakthrough pain: a meta-analysis of comparative trials. Breakthrough cancer pain (BTcP) is widely recognized as a clinically significant complication of chronic cancer pain. With most BTcP episodes peaking in intensity within a few minutes and lasting for approximately 30 minutes, speed of onset is crucial for effective pain management. Although the last decade has seen the development of a number of rapid-onset fentanyl preparations, BTcP is still typically managed by supplemental or rescue doses of the patient's around-the-clock medication, such as oral morphine. Importantly, although the fentanyl preparations, such as fentanyl buccal tablet (FBT), sublingual fentanyl citrate orally disintegrating tablet (ODT), and oral transmucosal fentanyl citrate lozenge (OTFC), have all been proven to be efficacious in clinical studies, oral morphine has never been specifically tested in BTcP, other than as a comparator in studies of OTFC and fentanyl pectin nasal spray. To determine the relative contributions to pain relief from oral morphine and the fentanyl preparations using placebo as a common comparator. Relevant studies were identified by review of the literature and used in a mixed-treatment meta-analysis to indirectly compare fentanyl preparations, morphine, and placebo for the treatment of BTcP. Analysis incorporating the five relevant studies identified revealed that although the fentanyl preparations provide superior pain relief vs. placebo in the first 30 minutes after dosing (FBT provided an 83% probability of superior pain relief, ODT 66%, and OTFC 73% vs. placebo), oral morphine performed little better than placebo (56% probability). This mixed-treatment analysis suggests that FBT, ODT, and OTFC might provide more efficacious treatment options than oral morphine for BTcP.

Decision-making involvement of individuals with dementia. Research underscores how autonomy and decision-making involvement may help to enhance the quality of life of older adults; however, individuals with dementia are often excluded from decision making that is related to their daily functioning. In this study we use a modified version of the Stress Process Model to consider the stress process of individuals with chronic illness, and in particular to explore the predictors of decision-making involvement among individuals with dementia (n = 215). We collected data from individual with dementia (IWD)-family caregiver dyads. Relying primarily on data from the IWD, we used hierarchical multiple regression analysis to determine the predictors of the IWD's decision-making involvement. Results indicate that individuals who report more decision-making involvement are younger, female, have more education, have a nonspousal caregiver, have fewer months since their diagnosis, exhibit fewer problems with activities of daily living and fewer depressive symptoms (based on caregiver report), and place more importance on autonomy/self-identity. In our discussion we examine the importance of autonomy and impairment levels for understanding the decision-making involvement of persons with dementia.

The paramedian supracerebellar-transtentorial approach to remove a posterior fusiform gyrus arteriovenous malformation. This is the case of a 14-year-old female who presented with headache and seizures. Cranial magnetic resonance imaging revealed an arteriovenous malformation (AVM) located at the posterior portion of the right-sided fusiform gyrus. Cerebral angiography showed that the AVM was fed mainly by branches from the inferior temporal trunk of the posterior cerebral artery. The main venous drainage was to the right transverse sinus through the tentorial vein. The AVM was totally excised through the paramedian supracerebellar-transtentorial approach with the patient in a semisitting position. Postoperative MRI and cerebral angiography confirmed the total resection. The patient was discharged on the 5th postoperative day without neurological deficit. The video can be found here: https://youtu.be/QPrUl8AP7G8 .

Shoulder arthrodesis by external fixation. The choice of pin site in shoulder arthrodesis after brachial plexus injury is important for efficient external fixation. The pins are inserted into the coracoid process from the anterior aspect and the scapular spine from the acromion. This insertion method holds the scapula more rigid and allows the patient to lie supine. Moreover, it makes it possible to correct the fixation angle after the operation. In 11 cases of brachial plexus injury, solid bony arthrodesis was obtained within three months.

Malignant peripheral primitive neuroectodermal tumor (PNET) of the kidney. We describe a 61-year-old patient with primitive neuroectodermal tumor (PNET) arising from the kidney. Despite intensive treatment including surgery, combination chemotherapy and radiotherapy, rapid progression of the tumor was encountered and the patient died within six months with widespread disease. This appears to be the first recorded case of PNET of the kidney.

The Functional Movement Screen: a reliability study. Reliability study. To determine intrarater test-retest and interrater reliability of the Functional Movement Screen (FMS) among novice raters. The FMS is used by various examiners to assess movement and predict time-loss injuries in diverse populations (eg, youth to professional athletes, firefighters, military service members) of active participants. Unfortunately, critical analysis of the reliability of the FMS is currently limited to 1 sample of active college-age participants. Sixty-four active-duty service members (mean ± SD age, 25.2 ± 3.8 years; body mass index, 25.1 ± 3.1 kg/m2) without a history of injury were enrolled. Participants completed the 7 component tests of the FMS in a counterbalanced order. Each component test was scored on an ordinal scale (0 to 3 points), resulting in a composite score ranging from 0 to 21 points. Intrarater test-retest reliability was assessed between baseline scores and those obtained with repeated testing performed 48 to 72 hours later. Interrater reliability was based on the assessment from 2 raters, selected from a pool of 8 novice raters, who assessed the same movements on day 2 simultaneously. Descriptive statistics, weighted kappa (κw), and percent agreement were calculated on component scores. Intraclass correlation coefficients (ICCs), standard error of the measurement, minimal detectable change (MDC95), and associated 95% confidence intervals (CIs) were calculated on composite scores. The average ± SD score on the FMS was 15.7 ± 0.2 points, with 15.6% (n = 10) of the participants scoring less than or equal to 14 points, the recommended cutoff for predicting time-loss injuries. The intrarater test-retest and interrater reliability of the FMS composite score resulted in an ICC3,1 of 0.76 (95% CI: 0.63, 0.85) and an ICC2,1 of 0.74 (95% CI: 0.60, 0.83), respectively. The standard error of the measurement of the composite test was within 1 point, and the MDC95 values were 2.1 and 2.5 points on the 21-point scale for interrater and intrarater reliability, respectively. The interrater agreement of the component scores ranged from moderate to excellent (κw = 0.45-0.82). Among novice raters, the FMS composite score demonstrated moderate to good interrater and intrarater reliability, with acceptable levels of measurement error. The measures of reliability and measurement error were similar for both intrarater reliability that repeated the assessment of the movement patterns over a 48-to-72-hour period and interrater reliability that had 2 raters assess the same movement pattern simultaneously. The interrater agreement of the FMS component scores was good to excellent for the push-up, quadruped, shoulder mobility, straight leg raise, squat, hurdle, and lunge. Only 15.6% (n = 10) of the participants were identified to be at risk for injury based on previously published cutoff values.

Genetic structure of Phaeosphaeria nodorum populations in the north-central and midwestern United States. Stagonospora nodorum blotch, caused by Phaeosphaeria nodorum, is considered one of the most destructive foliar diseases of wheat in the United States. However, relatively little is known about the population biology of this fungus in the major wheat-growing regions of the central United States. To rectify this situation, 308 single-spore isolates of P. nodorum were analyzed from 12 populations, five from hard red spring wheat cultivars in Minnesota and North Dakota and seven from soft red winter wheat in Indiana and Ohio. The genetic structure of the sampled populations was determined by analyzing polymorphisms at five microsatellite or simple-sequence repeat (SSR) loci and the mating type locus. Although a few clones were identified, most P. nodorum populations had high levels of gene (H(S) = 0.175 to 0.519) and genotype (D = 0.600 to 0.972) diversity. Gene diversity was higher among isolates collected from spring wheat cultivars in North Dakota and Minnesota (mean H(S) = 0.503) than in those from winter wheat cultivars in Indiana and Ohio (H(S) = 0.269). Analyses of clone-corrected data sets showed equal frequencies of both mating types in both regional and local populations, indicating that sexual recombination may occur regularly. However, significant gametic disequilibrium occurred in three of the four populations from North Dakota, and there was genetic differentiation both within and among locations. Genetic differentiation between the hard red spring and soft red winter wheat production regions was moderate (F(ST) = 0.168), but whether this is due to differences in wheat production or to geographical variation cannot be determined. These results suggest that sexual reproduction occurs in P. nodorum populations in the major wheat-growing regions of the central United States, and that geographically separated populations can be genetically differentiated, reflecting either restrictions on gene flow or selection.

Traces: making sense of urodynamics testing--part 13: pediatric urodynamics. While the majority of urodynamics studies are performed in adults with stress, urge, and mixed urinary incontinence or urinary retention, urodynamic clinicians are also expected to evaluate special populations. Article 13 of the Traces series focuses on urodynamics testing techniques in infants and children, including children with neurogenic bladder dysfunction.

Metagenomics shows that low-energy anaerobic-aerobic treatment reactors reduce antibiotic resistance gene levels from domestic wastewater. Effective domestic wastewater treatment is among our primary defenses against the dissemination of infectious waterborne disease. However, reducing the amount of energy used in treatment processes has become essential for the future. One low-energy treatment option is anaerobic-aerobic sequence (AAS) bioreactors, which use an anaerobic pretreatment step (e.g., anaerobic hybrid reactors) to reduce carbon levels, followed by some form of aerobic treatment. Although AAS is common in warm climates, it is not known how its compares to other treatment options relative to disease transmission, including its influence on antibiotic resistance (AR) in treated effluents. Here, we used metagenomic approaches to contrast the fate of antibiotic-resistant genes (ARG) in anaerobic, aerobic, and AAS bioreactors treating domestic wastewater. Five reactor configurations were monitored for 6 months, and treatment performance, energy use, and ARG abundance and diversity were compared in influents and effluents. AAS and aerobic reactors were superior to anaerobic units in reducing ARG-like sequence abundances, with effluent ARG levels of 29, 34, and 74 ppm (198 ppm influent), respectively. AAS and aerobic systems especially reduced aminoglycoside, tetracycline, and β-lactam ARG levels relative to anaerobic units, although 63 persistent ARG subtypes were detected in effluents from all systems (of 234 assessed). Sulfonamide and chloramphenicol ARG levels were largely unaffected by treatment, whereas a broad shift from target-specific ARGs to ARGs associated with multi-drug resistance was seen across influents and effluents. AAS reactors show promise for future applications because they can reduce more ARGs for less energy (32% less energy here), but all three treatment options have limitations and need further study.

Biological effect-test systems for the early recognition of unexpected environmental changes. Pre-marketing assessments of chemicals regarding their potential environmental impacts contain numerous sources of error and uncertainties. Practices and methods for the evaluation of environmental risks posed by individual pre-selected agents seem unsuitable for detecting unexpected trends in the environment. This is particularly so in view of the multitude of anthropogenic assaults on the environment and their complex interactions. Therefore, requirements for symptom-oriented biological effect-test systems, 'bioprobes', capable of reacting sensitively to environmental changes of unknown origin were conceived. Bioprobes designed to detect biological effects should respond to a broad spectrum of anthropogenic chemicals. They are environmental quality measuring devices consisting of cultivated organisms, cells, organelles or biomolecules in combination with recording units. In contrast to traditional biotests for chemical testing, bioprobes are deliberately exposed to selected segments of the environment for certain periods of time. During and after such exposures, changes of defined biological states or process rates-'observation elements'-are registered.

Characteristics of Patients Referred to a Pediatric Infectious Diseases Clinic With Unexplained Fever. Older case series established diagnostic considerations for children meeting a priori definitions of fever of unknown origin (FUO). No recent study has examined the final diagnoses of children referred for unexplained fever. This study was conducted with a retrospective chart review of patients referred to a pediatric infectious diseases clinic from 2008 to 2012 for unexplained fever. Sixty-nine of 221 patients were referred for "prolonged" unexplained fever. Ten of these were not actually having fever, and 11 had diagnoses that were readily apparent at the initial visit. The remaining 48 were classified as having FUO. The median duration of reported fever for these patients was 30 days; 15 had a diagnosis made, 5 of which were serious. None of the serious FUO diagnoses were infections. Of 152 patients with "recurrent" unexplained fever, 92 had an "intermittent" fever pattern, and most of these had sequential, self-limited viral illnesses or no definitive diagnosis made. Twenty of the 60 patients with a "periodic" fever pattern were diagnosed with periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome. Overall, 166 patients either were not having fever, had self-limited illnesses, or ultimately had no cause of fever discovered. Only 12 had a serious illness, 2 of which were infections (malaria and typhoid fever). Most children referred with unexplained fever had either self-limited illnesses or no specific diagnosis established. Serious diagnoses were unusual, suggesting that these diagnoses rarely present with unexplained fever alone, or that, when they do, the diagnoses are made by primary care providers or other subspecialists.

Non-muscarinic effects of scopolamine on N1E-115 neuroblastoma cells. Membrane effects of scopolamine on N1E-115 neuroblastoma cells were studied using intracellular recording techniques. Scopolamine in concentrations of 50 nM-1 microM induced a depolarization together with a decreased cell input resistance. This response had a reversal potential at +10 to +20 mV in a medium with normal sodium concentration (146.5 mM), and a reversal potential around -10 mV when the sodium concentration in the medium was lowered to 80 mM. The scopolamine-induced depolarization could not be blocked by carbachol (100 microM), and had a reversal potential at +10 to +20 mV. The simplest explanation of the results obtained is that scopolamine increases the membrane permeability for sodium and potassium, in a manner which is not related to muscarinic cholinergic receptors.

Passive diffusion of weak organic electrolytes across Caco-2 cell monolayers: uncoupling the contributions of hydrodynamic, transcellular, and paracellular barriers. A systematic approach was used to demonstrate the quantitative interplay of pH, pKa, lipophilicity, charged and uncharged molecular species, molecular size, aqueous diffusivity, and stirring in passive transport across the aqueous boundary layer, microporous filter support, and transcellular and paracellular barriers in Caco-2 cell monolayers. The relationship of permeability of the aqueous boundary layer and hydrodynamic stirring was elucidated from transmonolayer fluxes of testosterone. Adrenergic receptor antagonists including propranolol (PPL), alprenolol (APL), pindolol (PDL), and atenolol (ATL) represented the model series of structurally similar weak bases with pKa values between 8.8 and 9.65. Although intrinsically lipophilic, their apparent log PC (n-octanol/water) at pH 7.4 and 6.5 ranged from -2.6 to 1.3. Effective permeability coefficients (Pe) correlated with log PC at both pH 7.4 and 6.5 showing a single sigmoidal-like curve: PPL > APL > PDL > or = ATL. The Pe approached a minimum plateau value established by the protonated ATL for the paracellular route (pore radius of 12 A) by molecular size-restricted diffusion within a negative electrostatic field of force. The Pe of the weak bases was delineated into component permeability coefficients of the aqueous boundary layer and porous filter support, the intrinsic permeabilities of charged and uncharged species for the transcellular and paracellular routes, and the extent to which the routes were utilized at each pH. This study emphasized a generally applicable approach to quantitatively analyze passive transport data on weak organic electrolytes and neutral molecules generated using cell culture monolayers.

Swimming training promotes cardiac remodeling and alters the expression of mRNA and protein levels involved in calcium handling in hypertensive rats. The aim of this study was to identify the effects of swimming training on the mRNA expression and protein levels of the calcium handling proteins in the hearts of renovascular hypertensive rats submitted to swimming protocol during 6 weeks. Fischer rats with renovascular hypertension 2-kidney 1-clip (2K1C) and SHAM groups were divided among sedentary and exercised groups. The exercise protocol lasted for 6 weeks (1 h/day, 5×/week), and the mean arterial pressure, cardiomyocytes hypertrophy parameters, mRNA expression and protein levels of some calcium handling proteins in the left ventricle were evaluated. Swimming training was able to reduce the levels of mean arterial pressure in the hypertensive group compared to 2K1C SED, and to promote cardiac hypertrophy in SHAM EX and 2K1C EX groups in comparison to the respective control groups. The mRNA levels of B-type natriuretic peptide were reduced in the 2K1C EX when compared to 2K1C SED. The mRNA and protein levels of the sarcoplasmic reticulum Ca2 +-ATPase increased after the swimming training in SHAM and 2K1C groups. The mRNA and protein levels of phospholamban, displayed an increase in their levels in the exercised SHAM and in hypertensive rats in comparison to their respective controls; while mRNA levels of Na+/Ca2 + exchanger was reduced in the left ventricle comparing to the sedentary hypertensive rats. Taken altogether, we provide evidence that the aerobic training may lead to cardiac remodeling, and modulate the calcium handling proteins expression in the heart of hypertensive rats.

Variability of the parahippocampal surface of the transverse fissure in the human brain. The parahippocampal (ventral) surface of the lateral part of the transverse fissure (LTF), formed by the parahippocampal gyrus, was examined in 53 human brain hemispheres without pathological changes. Cytoarchitectonics of this region was studied on the frontal histological sections stained either with cresyl violet or with Weil method. Four types of the shape of the parahippocampal surface of LTF were distinguished. In type 1 the surface is either flat or elevated in its medial part (medial eminence; 34.0%). In type 2 the surface is elevated in its lateral part (lateral eminence, 24.5%). In type 3 there are two eminences--the lateral and the medial; both of similar height (20.8%). In type 4 the lateral eminence is distinctly higher than the medial one (20.7%). The eminences contain cytoarchitectonically different structures. The lateral eminence is formed mainly by the subiculum and CA1 area, the medial by the presubicular region. The shape of the parahippocampal surface of LTF may be of importance in assessment of the Alzheimer's disease pathology.

[Septic arthritis: practical diagnosis and new treatments]. Septic arthritis remains a major challenge to physicians because the increasing frequency of certain microorganisms to become in antibiotic-resistant and persistent difficulties regarding both early diagnostics and proper treatment of subjects with joint infections. This paper will review current diagnostics test and their contribution to the rapid evaluation of joint infection. Importantly, updated therapeutic suggestions will be presented which, when appropriately applied, should diminish the risks of sequelae following infectious arthritis.

Barriers to involving GP Speciality Trainees in the teaching of medical students in primary care: the GP trainer perspective. Involvement in teaching activities is a curriculum requirement for GP Speciality Trainees (GPSTs). There are numerous potential benefits to involving GPSTs in teaching, including mutual educational benefit for both GPST and learner. However, GPSTs on placement in primary care may be less involved in teaching activities than hospital-based trainees. The reasons for this are not fully understood. This multi-site study aimed to explore the perceptions of GP trainers of the barriers to involving GPSTs in teaching in primary care. Focus groups of General Practice (GP) trainers from four regional GP training programmes across Northern England were conducted. Data were analysed thematically. Trainers cited barriers relating to the trainee (e.g. capacity and capability), practice (e.g. capacity), and teaching (e.g. appropriateness of teaching methods). Underlying these barriers, there appeared to be a cultural attitude towards GPST involvement in teaching: trainers viewed teaching as an extraneous rather than integral part of GP training, considered teaching to represent a deviation from the norm and felt that the GPST was restricted to a learner role. Whilst attempts to address the practical barriers identified in this study are required, a cultural shift in which the role of the GPST as a teacher becomes normalised is urgently needed.

A pilot study on safety climate in Chinese hospital. The present paper has 2 primary objectives as a pilot study on health-care safety climate in China: to develop its prototypical model well fit to the country's current hospital situations and validated external reliability and to elicit essential characteristics of safety climate for hypothetical general features in Chinese health care. A safety climate survey was carried out in 2008 at a university hospital in Shanghai, using an Operating Room Management Attitudes Questionnaire. We collected 1056 valid responses from doctors and nurses with 81% of overall response rate. A 9-dimension model of safety climate was developed by applying principal component analysis to the entire sample with 44% of cumulative variance accounted for. Compared with the Japanese sample, safety climate in the Chinese hospital was characterized as strong awareness of own competence, positive attitudes to organization, but large power distance and unrealistic staff recognition of human error. Criterion validity of the construct was in part assured by significant correlations of 4 dimensions with self-reported staff behavior of accident reporting. Safety climate has been not yet mature in the hospital surveyed that might be partly tied with blame culture. Considering health-care policies, procedures, and management styles shared with many other health-care organizations as well as Chinese culture, we would hypothesize that the immature nature is common in Chinese health care as overall characteristics of safety climate. From these results, we would suggest that a nonpunitive health-care culture should be fostered to improve patient safety in China.

Motor unit action potential rate and motor unit action potential shape properties in subjects with work-related chronic pain. The objective of this study was to investigate differences in motor control of the trapezius muscle in cases with work-related chronic pain, compared to healthy controls. Ten cases with chronic pain and 13 controls participated in the study. Electromyographic (EMG) signals were recorded from the upper trapezius during five computer work-related tasks. Motor control was assessed using global root-mean-square value (RMS(G)), motor unit action potential (MUAP) rate (number of MUAPs per second, MR) and two MUAP shape parameters, i.e. root-mean-square (RMS(MUAP)) and median frequency (FMED(MUAP)). MR and FMED(MUAP) were higher for the cases than for the controls (P < 0.05). RMS(MUAP) showed a trend for higher values in the chronic pain group (P < 0.13), whereas RMS(G) did not show a significant difference between the groups. The higher MR, FMED(MUAP) and the trend for higher RMS(MUAP) suggest that more high-threshold MUs contribute to low-level computer work-related tasks in chronic pain cases. Additionally, the results suggest that the input of the central nervous system to the muscle is higher in the cases with chronic pain.

Domino effect analysis using Bayesian networks. A new methodology is introduced based on Bayesian network both to model domino effect propagation patterns and to estimate the domino effect probability at different levels. The flexible structure and the unique modeling techniques offered by Bayesian network make it possible to analyze domino effects through a probabilistic framework, considering synergistic effects, noisy probabilities, and common cause failures. Further, the uncertainties and the complex interactions among the domino effect components are captured using Bayesian network. The probabilities of events are updated in the light of new information, and the most probable path of the domino effect is determined on the basis of the new data gathered. This study shows how probability updating helps to update the domino effect model either qualitatively or quantitatively. The methodology is applied to a hypothetical example and also to an earlier-studied case study. These examples accentuate the effectiveness of Bayesian network in modeling domino effects in processing facility.

Prognostic factors in ovarian cancer. Epithelial ovarian cancers vary considerably in their biologic behavior and this is reflected in the variety of clinicopathologic factors that are used for predicting outcome. This article assesses the potential value of some of the newer prognostic factors and critically evaluates the more commonly used clinicopathologic variables.

Design, synthesis, and bioactivity of pyrazole acid derivatives as endothelin receptor antagonists. A series of novel pyrazole carboxylic acid derivatives was designed and synthesized, and their antagonism effect on endothelin (ET)-1-induced contraction in the rat thoracic aortic ring was screened. The radio receptor assay was used to examine the potency of the compounds on ET receptor. Some target compounds demonstrated significant inhibitory activity, especially 7m, which showed a potent inhibition percentage higher than the contrast compound BQ123. Further assays on the binding and selectivity for ET showed that 7m had highly potent binding activity on ETA at the nanomole level, and the ratio of ETA/ETB was 36. Therefore, we inferred that 7m was a non-selective antagonist of ETA and ETB and had potential for further development in cardiovascular diseases.

Effect of 1-(2,4-dichlorobenzyl)-indazole-3-carboxylic acid on sperm tails in rhesus monkeys. Large numbers of spermatozoa with bent or coiled tails were found in the ejaculates of rhesus monkeys treated with 1-(2,4-dichlorobenzyl-indazole-3-carboxylic acid (DICA) (50 or 500 mg/kg for various periods). The defect appeared only in spermatozoa in the cauda epididymidis and consisted of axoneme disarrangement and loss of the fibre doublets. The coil was completely enclosed in a membrane.

Solution-Synthesized High-Mobility Tellurium Nanoflakes for Short-Wave Infrared Photodetectors. Two-dimensional (2D) materials, particularly black phosphorus (bP), have demonstrated themselves to be excellent candidates for high-performance infrared photodetectors and transistors. However, high-quality bP can be obtained only via mechanical exfoliation from high-temperature- and high-pressure-grown bulk crystals and degrades rapidly when exposed to ambient conditions. Here, we report solution-synthesized and air-stable quasi-2D tellurium (Te) nanoflakes for short-wave infrared (SWIR) photodetectors. We perform comprehensive optical characterization via polarization-resolved transmission and reflection measurements and report the absorbance and complex refractive index of Te crystals. It is found that this material is an indirect semiconductor with a band gap of 0.31 eV. From temperature-dependent electrical measurements, we confirm this band-gap value and find that 12 nm thick Te nanoflakes show high hole mobilities of 450 and 1430 cm2 V-1 s-1 at 300 and 77 K, respectively. Finally, we demonstrate that despite its indirect band gap, Te can be utilized for high-performance SWIR photodetectors by employing optical cavity substrates consisting of Au/Al2O3 to dramatically increase the absorption in the semiconductor. By changing the thickness of the Al2O3 cavity, the peak responsivity of Te photoconductors can be tuned from 1.4 μm (13 A/W) to 2.4 μm (8 A/W) with a cutoff wavelength of 3.4 μm, fully capturing the SWIR band. An optimized room-temperature specific detectivity ( D*) of 2 × 109 cm Hz1/2 W-1 is obtained at a wavelength of 1.7 μm.

Effect of caseload on the short-term outcome of colon surgery: results of a multicenter study. This prospective multicenter study investigated the effect of hospital caseload on early postoperative outcome of surgery for carcinoma of the colon in 75 German hospitals and included 2293 patients. The hospitals were divided into those with a caseload of 1-30 (group A), 31-60 (group B), and more than 60 (group C) operations. Increasing caseload was associated only with fewer general postoperative complications. It was also associated with significantly greater use of antibiotic prophylaxis. No significant differences between the groups were found in resection rates, intraoperative complications, specific postoperative complications, overall postoperative morbidity, hospital mortality, or 30-day mortality. The significance of hospital caseload for the short-term postoperative outcome following surgery on the colon should not be overestimated. Basing conclusions about the results to be expected simply on the case volume is impermissible. On the basis of the available data it is not possible to establish a threshold value, that is, a minimum number of required operations.

Accelerated degradation of junctional acetylcholine receptor-alpha-bungarotoxin complexes in denervated rat diaphragm. [125] alpha-bungarotoxin was administered to rats in vivo to label acetylcholine receptor in innervated diaphragm, 5-day denervated diaphragm, or diaphragm which had been denervated immediately before labeling. The rate of degradation of junctional toxin-receptor complexes was followed by sacrificing animals at various times after labeling. The rate of degradation of junctional toxin-receptor complexes was significantly faster in 5-day denervated left hemidiaphragm (t 1/2=2.0 days) than in innervated left hemidiaphragm (t 1/2=10.7 days). The rate of degradation of junctional toxin-receptor complexes in left hemidiaphragm denervated at the time of labeling was essentially identical to that in innervated muscle for 3 days but then increased to a significantly more rapid rate (t 1/2=3.7 days in the period 3.13 days after denervation and labelling). These findings support the concept that continuous innervation is needed to maintain the metabolic stability of junctional acetylcholine receptors.

Effects of whole-body exposure to 915 MHz RFID on secretory functions of the thyroid system in rats. As a part of an investigation on the potential risks of radiofrequency identification (RFID) on human health, we studied whether exposure to 915 MHz RFID in rats significantly affected the secretory function of the thyroid system. A reverberation chamber was used as a whole-body exposure system. Male Sprague-Dawley rats were exposed for 8 h per day, 5 days per week, for a duration of 2, 4, 8, or 16 weeks. The estimated whole-body average specific absorption rate (SAR) varied from 3.2 to 4.6 W/kg depending on the age/mass of the animals for the field of the 915 MHz RFID reader. Plasma levels of triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) were evaluated via enzyme-linked immunosorbent assay. Morphological changes in the thyroid gland were then analyzed. No changes in T3, T4, or TSH were observed over time between the sham- and RFID-exposed groups. We suggest that subchronic exposure to 915 MHz RFID at a SAR of 4 W/kg does not cause significant effects on thyroid secretory function.

The Experiences of People with Dementia and Their Caregivers in Dementia Diagnosis. People can live well with dementia if they are diagnosed early and receive early interventions and appropriate dementia management and care. However, dementia is currently under-detected and under-diagnosed. The diagnosis rate is around 50% only in higher-income countries and 5-10% only in low- and middle-income countries. Studies on consumers' experiences in engaging in dementia diagnosis in a socio-cultural context are much needed in order to generate research evidence to inform person-centered dementia care and services. The aim of the study was to understand the experiences of people with dementia and their caregivers in engaging in dementia diagnosis. An interpretative study design informed by Gadamer's hermeneutic principles was applied to the present study to achieve the aim of the study. The study was strengthened by applying a social ecological framework to the study design. In total, 23 participants contributed to the interviews or focus group. Thematic analysis was applied to data analysis. Four themes were determined from data and described as: capabilities to detect the memory loss in an early stage, perceptions and beliefs of dementia in the community, different journeys toward the diagnosis and expectations of a smooth journey for others. These findings illuminate a social ecological perspective of improving early detection and timely diagnosis of dementia in the community settings. The findings of this study have implications for policy, resource, and practice development. Consumers expect that government subsidized dementia care services in primary care and specialist care settings are needed in order to enable consumer-driven timely diagnosis and dementia management in home care settings.

Differential ecophysiological response of a major Mediterranean pine species across a climatic gradient. The rate of migration and in situ genetic variation in forest trees may not be sufficient to compete with the current rapid rate of climate change. Ecophysiological adjustments of key traits, however, could complement these processes and allow sustained survival and growth across a wide range of climatic conditions. This was tested in Pinus halepensis Miller by examining seven physiological and phenological parameters in five provenances growing in three common garden plots along a climatic transect from meso-Mediterranean (MM) to thermo-Mediterranean (TM) and semi-arid (SA) climates. Differential responses to variations in ambient climatic conditions were observed in three key traits: (i) growing season length decreased with drying in all provenances examined (from 165 under TM climate to 100 days under SA climate, on average); (ii) water use efficiency (WUE) increased with drying, but to a different extent in different provenances, and on average from 80, to 95, to 110 µmol CO(2) mol(-1) H(2)O under MM, TM and SA climates, respectively; (iii) xylem native embolism was stable across climates, but varied markedly among different provenances (percent loss of conductivity, was below 5% in two provenances and above 35% in others). The results indicated that changes in growing season length and WUE were important contributors to tree growth across climates, whereas xylem native embolism negatively correlated with tree survival. The results indicated that irrespective of slow processes (e.g., migration, genetic adaptation), the capacity for ecophysiological adjustments combined with existing variations among provenances could help sustain P. halepensis, a major Mediterranean tree species, under relatively extreme warming and drying climatic trends.

Intracellular concentrations and ouabain-induced fluxes of sodium and potassium in erythrocytes of normotensive Zimbabweans. Intracellular Na and K concentrations as well as ouabain-induced transmembrane net Na and K fluxes were measures in erythrocytes (TBC) of 22 adult Black male Zimbabweans. The intracellular Na concentration was 9.1 +/- 0.44 mmol/l RBC, the K concentration 90.7 +/- 1.33 mmol/l RBC and the ouabain (0.1 mM)-induced Na influx 1.55 +/- 0.132 mmol/hr.1 RBC. The intracellular Na concentration is higher than most values reported from studies of Whites, but the intracellular K concentration and the ouabain-induced Na influx compare with literature values. No significant correlation was found between intracellular Na concentration and blood pressure.

Co-production of fumaric acid and chitin from a nitrogen-rich lignocellulosic material - dairy manure - using a pelletized filamentous fungus Rhizopus oryzae ATCC 20344. Fumaric acid is widely used as a food additive for flavor and preservation. Rhizopus oryzae ATCC 20344 is a fungus known for good fumaric acid production. It also has been reported that the fungal biomass has high chitin content. This study investigated the possibility of producing both fumaric acid and chitin via R. oryzae fermentation of dairy manure. Co-production of valuable bio-based chemicals such as fumaric acid and chitin could make the utilization of manure more efficient and more profitable. A three step fermentation process was developed which effectively utilized the nitrogen as well as the carbohydrate sources within the manure. These steps were: the culturing of pellet seed; biomass cultivation on liquid manure to produce both biomass and chitin; and fumaric acid production on the hydrolysate from the manure fiber. Under the identified optimal conditions, the fermentation system had a fumaric acid yield of 31%, and a biomass concentration of 11.5 g/L that contained 0.21 g chitin/g biomass.

Antibodies against haptens in the study of structure and biological activity of growth hormone. The alpha-amino group of bovine Growth Hormone was selectively modified with TNBS with no detectable changes in growth promoting activity. TNP was used as hapten for the production of antibodies against the end terminal region of bGH. The region near the alpha-amino group is not involved in the binding of bGH to rat liver cells, and it seems to be away from the part of the molecule that interacts with the cell binding sites.

Speciated hydrocarbon and carbon monoxide emissions from an internal combustion engine operating on methyl tertiary butyl ether-containing fuels. In the present work, engine and tailpipe (after a three-way catalytic converter) emissions from an internal combustion engine operating on two oxygenated blend fuels [containing 2 and 11% weight/weight (w/w) methyl tertiary butyl ether (MTBE)] and on a nonoxygenated base fuel were characterized. The engine (OPEL 1.6 L) was operated under various conditions, in the range of 0-20 HP. Total unburned hydrocarbons, carbon monoxide, methane, hexane, ethylene, acetaldehyde, acetone, 2-propanol, benzene, toluene, 1,3-butadiene, acetic acid, and MTBE were measured at each engine operating condition. As concerns the total HC emissions, the use of MTBE was beneficial from 1.90 to 3.81 HP, which were by far the most polluting conditions. Moreover, CO emissions in tailpipe exhaust were decreased in the whole operation range with increasing MTBE in the fuel. The greatest advantage of MTBE addition to gasoline was the decrease in ethylene, acetaldehyde, benzene, toluene, and acetic acid emissions in engine exhaust, especially when MTBE content in the fuel was increased to 11% w/w. In tailpipe exhaust, the catalyst operation diminished the observed differences. Ethylene, methane, and acetaldehyde were the main compounds present in exhaust gases. Ethylene was easily oxidized over the catalyst, while acetaldehyde and methane were quite resistant to oxidation.

Predicted high-energy molecules: helical all-nitrogen and helical nitrogen-rich ring clusters. Helical all-nitrogen and nitrogen-rich ring clusters, new types of potential high-energy molecules, were investigated in the computational study reported here. Stable helical all-nitrogen clusters N26 and N46 and nitrogen-rich helical structure N26H16 formed by fused six-membered rings were found and characterized as proper energy minima by having real frequencies for all eigenvectors of the Hessian matrix. Furthermore, the stability of [6] N-ring helix was studied by calculating the barrier of dissociation reaction. The potential of these type molecules as high-energy density materials was studied. For a better intuitive understanding of the unusual bonding patterns, the molecular isodensity contour (MIDCO) surfaces for [6] N-ring helix and [6] N-helicene were compared at some characteristic density threshold values of 0.20, 0.32, and 0.35 au. As indicated at these threshold values of the isodensity surfaces, the bonds of all-nitrogen clusters appear stronger than those of nitrogen-rich clusters. Apparently, the nitrogen-rich clusters are of higher energy than the all-nitrogen structures, especially if one takes into account the energy balance of bonds involving hydrogen.

Increased levels of NAD(P)H: quinone oxidoreductase 1 (NQO1) in pancreatic tissues from smokers and pancreatic adenocarcinomas: A potential biomarker of early damage in the pancreas. NAD(P)H:quinone oxidoreductase 1 (NQO1) is elevated in several human tumors. This study was conducted to determine whether increased levels of NQO1 expression also occur in human pancreatic tumor tissue, and to compare expression levels in nontumorous tissue from smokers with those in nonsmokers. The expression of NQO1 was examined in pancreatic tissue samples from 82 human donors. These samples included normal (n = 20), smokers (n = 25), pancreatitis (n = 7), and adenocarcinomas of the pancreas (n = 30). Genotyping for the C609T polymorphism in NQO1 by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was also performed. Polymorphic variants were confirmed by automatic sequencing. Higher levels of NQO1 expression were demonstrated in pancreatic adenocarcinomas (0.831 +/- 0.021) compared to those in nontumorous tissues from nonsmokers (0.139 +/- 0.024). These high levels were also found in smokers (0.729 +/- 0.167) and in pancreatitis tissues (0.923 +/- 0.184). NQO1 activity was also higher in smokers (2.43 +/- 0.61 nmol/min per mg protein) compared to nonsmokers (0.44 +/- 0.05 nmol/min per mg protein; p < 0.05). No differences were found in genotype distribution and frequencies of the variant alleles between normal and cancer tissues in this relatively small sample pool. Seventy-five percent of the normal pancreatic tissues showed 609(C/C) and 25% 609(C/T). In pancreatic adenocarcinomas the frequency distribution was 65% C/C, 30% C/T and 5% T/T. The increased expression in noncancer pancreatic tissue from smokers and the fact that smoking is a moderate risk factor for pancreatic cancer suggest that NQO1 expression may be a good candidate as a biomarker for pancreatic cancer, especially in risk groups such as smokers.

[Patients on chemotherapy: depression and adherence to treatment]. This analytical, cross-sectional study applied a quantitative approach to verify the presence of depression and the adherence to a chemotherapy treatment in patients with cancer at the central chemotherapy pharmacy of a university hospital. The sample consisted of 102 patients, and data were collected from October 2010 to May 2011. A structured interview was used to obtain sociodemographic, clinical and therapeutic data; the Morisky Test and Beck Depression Inventory were also applied. The results revealed that 10.8% and 1.9% of participants had moderate and severe depression, respectively. The presence of depression was significantly associated with variables such as income per capita, the number of surgeries, and disease duration. A lack of treatment adherence was identified in 48% of participants. These results indicate the need for health staff training to detect depressive disorders and chemotherapy treatment attrition among patients with cancer.

Organic content influences sediment microbial fuel cell performance and community structure. This study constructed sediment microbial fuel cells (SMFCs) with different organic loadings without the amendment of external substrates, and it investigated how such variation affects electricity generation and microbial community structure. Results found sediment characteristics significantly influenced SMFC performance and appropriate organic content is important to maintain stable power outputs. SMFCs with loss of ignition (LOI) of 5% showed the most reliable performance in this study, while high organic content (LOI 10-16%) led to higher but very unstable voltage output because of biogas accumulation and worm activities. SMFCs with low organic content (1-3%) showed low power output. Different bacterial communities were found in SMFCs shown various power generation performance even those with similar organic contents. Thermodesulfovibrionaceae was found closely related to the system startup and Desulfobulbaceae showed great abundance in SMFCs with high power production.

Massive osteolysis of the cervical spine. A case report. This study described the course of a case of massive osteolysis (Gorham's disease) of the cervical spine and discussed the literature data. To describe a case of massive osteolysis of the cervical spine with fatal outcome and to discuss the classification of the disease among osteolysis and its therapeutic modalities. Massive osteolysis is a rare condition (fewer than 100 cases reported in the literature) of unknown etiology, which may involve any bone in the body, with a propensity for the shoulder and pelvic girdle. Few cases of cervical spine involvement were reported. The case of a 32-year-old man with fatal progressive massive osteolysis of the cervical spine despite multiple attempts to achieve surgical stabilization was reported. Massive osteolysis was characterized by complete destruction of all or part of a bone by angiomatous tissue and may have represented a local disturbance of osteoclastic activity. No successful therapy was proposed, and the prognosis of spine involvement was very poor. Massive osteolysis is a rare condition with no successful therapy. The hypothesis of involvement of circulating preosteoclasts in the osteolytic process may suggest treatment attempts with diphosphonates because of the futility of standard bone grafting techniques in spine involvement.

Suppression of mitochondrial respiratory function after short-term anoxia. Exposure of rat hepatocytes to 30 min anoxia resulted in a substantial decrease in O2 consumption on reoxygenation. Measurement of the sequestered Ca2+ pool of mitochondria by selective release with the protonophore, carbonylcyanide-p-trifluoromethoxyphenylhydrazone (FCCP), and quantitation with the metallochromic indicator, arsenazo III, showed that anoxia caused a marked decrease in mitochondrial Ca2+. This loss could, in part, be due to decreased electrophoretic uptake resulting from a 20% decrease in the magnitude of the mitochondrial transmembranal potential. The decrease was associated with a decrease in ATP synthase activity as expected from the Ca2+ dependence of endogenous inhibitor binding to the ATP synthase. These results show that short-term anoxia suppresses mitochondrial function in hepatocytes and suggest that mitochondrial Ca2+ content may be important in this regulation. Regulation of the ATP synthase and other ion transport systems may provide a means to preserve ion distribution and protonmotive force and thereby prolong the period during which cells can tolerate anoxia.

Response of human oligodendrocytes to interleukin-2. Interleukin 2 (IL-2) directly affects the function of both neurons and glia in the nervous system. It can induce proliferation and differentiation or cause cell death in oligodendrocytes. We have previously cloned the cDNAs for the alpha (alpha), beta (beta), and gamma (gamma) chains of the IL-2 receptor (IL-2R) complex from a human oligodendroglioma cell line TC620. In an effort to characterize the IL-2 receptor (IL-2R) on oligodendrocytes, experiments were performed using recombinant human IL-2 on normal human oligodendrocytes from adult brain tissue and the IL-2-responsive subclone TC620.6A2 of the oligodendroglioma line. The TC620 subclone has the phenotype of an immature oligodendrocyte. At 5 nM IL-2, there was a 2.5-fold increase in proliferation of both normal and malignant human oligodendrocytes. This response was receptor-mediated in that binding of 125I-IL-2 to TC620.6A2 cells detected a single receptor class for IL-2 with an affinity of 3.6 nM. Immunohistochemical staining of TC620.6A2 cells with a panel of monoclonal antibodies to different epitopes of the human IL-2R alpha chain demonstrated the presence of IL-2R alpha on the surface of these cells, in staining patterns which did not always coincide with those found on T cells. Neither the beta nor the gamma chain of the IL-2R complex was detected on human oligodendrocytes by immunohistochemistry. Those antibodies which recognized cell surface IL-2R alpha epitopes on TC620.6A2 blocked IL-2-induced proliferation, while those which did not detect cell surface IL-2R alpha epitopes were not inhibitory. This same panel of monoclonal antibodies, when used to probe membrane preparations of TC620.6A2 cells on a Western blot, detected three proteins of 100, 83, and 47 kDa, in contrast to the 55-kDa IL-2R alpha observed on T cells.

Effect of the Curvature of the Punches on the Shape of the Interface and the Delamination Tendency of Bilayer Tablets. Bilayer tablets are of special interest in the pharmaceutical industry. The main problem during their manufacturing is the occurrence of delamination during or after the ejection from the die. This work studies the influence of using punches with a curvature on the interfacial strength and thus on the delamination tendency of bilayer tablets. Bilayer tablets were produced with a compaction simulator using different flat and concave punches with different radii of curvature. The main compaction pressure was kept constant but the tamping force was varied. Two bilayer model systems were studied. The interfacial strength was determined using a previously described indentation test. The factors studied were analyzed for statistical significance with respect to the responses. The curvature of the interface was found to be higher when the curvature of the punch and the tamping force increased. Breaking tests then demonstrated that, for bilayer tablets obtained using the same compression parameters, the interfacial strength was lower when the curvature of the interface increased. As a consequence, when producing bilayer tablets with concave punches, it is important to choose properly the tableting parameters in order to have an interface between the layers as flat as possible to avoid delamination issues.

Role of microRNAs on adipogenesis, chronic low-grade inflammation, and insulin resistance in obesity. The aim of this review was to convey updated information on the role of microRNAs in adipogenesis, chronic low-grade inflammation, and insulin resistance in obesity. Obesity is a chronic disease characterized by the presence of metabolic disorders (e.g., low-grade chronic inflammation), which contributes to the manifestation of insulin resistance. Diverse molecular mechanisms have been implicated in the development of these disorders, and microRNAs stand out as a contributing factor. They are a class of noncoding RNAs that regulate the expression of genes by inducing cleavage of mRNAs or via inhibition of protein translation. It is important to point out that obese individuals show alterations in the expression of microRNAs favoring manifestation of the metabolic disorders present in these patients, and these alterations may be reversed by the loss of weight. Therefore, microRNAs may be regarded as potential biomarkers of obesity-related disorders. Further studies on this topic may advance the understanding of the molecular basis of obesity, including the participation of microRNAs in the pathogenesis of this disease.

Right ventricular remodeling after pulmonary valve replacement: early gains, late losses. Although early results of pulmonary valve replacement (PVR) after tetralogy of Fallot repair have been described, information about late postoperative ventricular size and function is lacking. This study was designed to characterize right ventricular (RV) remodeling up to 10 years after PVR. Retrospective analysis was conducted of cardiovascular magnetic resonance (CMR) data from 2002 to 2011 in 101 patients (244 studies) who underwent PVR and had one or more post-PVR CMR studies at five post-PVR time intervals up to 10 years. Compared with pre-PVR values, in the 0- to 1-year post-PVR group, pulmonary regurgitation (PR) fraction decreased from 49 ± 11% to 3 ± 2% (p < 0.001), RV end-diastolic volume index (EDVi) decreased by 39% (p < 0.001), RV end-systolic volume index (ESVi) decreased by 33% (p < 0.001), and RV ejection fraction (EF) decreased from 48 ± 8% to 44 ± 8% (p = 0.01). These values remained unchanged through the sixth post-PVR year. However, by 7 to 10 years after PVR (n = 15), RVEDVi and RVESVi were significantly increased and had returned to 84% and 104% of pre-PVR volumes, respectively, and RV EF had declined further. Increasing RV EDVi correlated with increasing grades of PR (rs = 0.36, p < 0.001), tricuspid regurgitation (rs = 0.33, p < 0.001), and RV pressure (rs = 0.32, p = 0.03). In this cohort, early reduction in RV size showed a gradual return toward preoperative values by 7 to 10 years after PVR. The late adverse RV remodeling was associated with increased RV volume and pressure loads. These findings highlight the palliative nature of PVR and the importance of continued surveillance.

Relationships between leucine and the pancreatic exocrine function for improving starch digestibility in ruminants. Four Holstein heifers (215 ± 7 kg; means ± SD), fitted with one pancreatic pouch, duodenal re-entrant cannulas, and duodenal infusion catheters, were used in this experiment. In phase 1, the 24-h profile of pancreatic fluid was determined. Pancreatic fluid flow peaked 1h after feeding, but peaks of similar magnitude also occurred before the morning feed, necessitating 24-h collection of pancreatic fluid to estimate daily excretion. In phase 2, the effects of duodenal infusions of 0, 10, 20, or 30 g of leucine on pancreatic fluid flow were determined in a 4 × 4 Latin square design. The leucine was infused for 12h in 2,500 mL of the infusate, and samples of pancreatic fluid and jugular blood were collected in 1-h intervals from the beginning of the infusion for 36 h. The results showed that the secretion rate of pancreatic fluid (mL/h) was significantly higher in 10-g leucine group than the other groups (mL/h). Protein concentration (mg/mL) in pancreatic fluid was elevated proportional to the amount of leucine infused. Leucine infusions increased both the concentration (U/mL) and secretion rate (U/h) of α-amylase. Infusion of 10 g of leucine also increased the secretion rates (U/h) of trypsin, chymotrypsin, and lipase, but did not change their concentrations. No significant effects of leucine infusions on plasma glucose and insulin concentrations were found. The results indicate that leucine could act as a nutrient signal to stimulate α-amylase production and pancreatic exocrine function in dairy heifers.

Pentastomids and the tetrapod lung. Pentastomids comprise a highly specialized taxon of arthropod-like parasites that probably became adapted to the lungs of amphibians and reptiles early in their long evolutionary history. Few other macroparasites exploit this particular niche. Pentastomids are often large, long-lived and yet they cause little observable pathology in lungs, despite being haematophagous. The lungs of all tetrapods are lined with pulmonary surfactant, a remarkable biological material consisting of a complex mixture of phospholipids, neutral lipids and proteins that has the unique ability to disperse over the air-liquid lining of the lung. In the lower tetrapods it acts as an anti-glue preventing adhesion of respiratory surfaces when lungs collapse during swallowing prey or upon expiration. In mammals, pulmonary surfactant also plays a critical role regulating the activity of alveolar macrophages, the predominant phagocytes of the lower airways and alveoli. This review outlines the evidence suggesting that lung-dwelling pentastomids, and also nymphs encysted in the tissues of mammalian intermediate hosts, evade immune surveillance and reduce inflammation by coating the chitinous cuticle with a their own stage-specific surfactant. The lipid composition of surfactant derived from lung instars of the pentastomid Porocephalus crotali cultured in vitro is very similar to that recovered from the lung of its snake host. Pentastomid surfactant, visualised as lamellate droplets within sub-parietal cells, is delivered to the cuticle via chitin-lined efferent ducts that erupt at a surface density of < 400 mm(-2). The fidelity of the system, which ensures that every part of the cuticle surface is membrane-coated, testifies to its strategic importance. Two other extensive glands discharge membrane-associated (hydrophobic?) proteins onto the hooks and head; some have been purified and partly characterized but their role in minimising inflammatory responses is, as yet, undetermined.

[Cooperative study on the long-term use of anti-anginal preparations (methodologic questions)]. The development of a national collaborative program for the study of long-term effects of antianginal drugs initiated for the first time in our country is reported. The present communication is concerned with methodological approaches to the study. The collaborative effort has enabled a basically new scale of research. The principal methodological problems discussed are: how to select antianginal drugs; how to assess drug tolerance; and, possible changes in pharmacokinetic parameters of antianginal drugs used on a long-term basis. Studies along these lines are expected to contribute to the development of optimum regimens of antianginal treatment.

Long-term safety and efficacy of risperidone in children with disruptive behaviour disorders. Results of a 2-year extension study. The aim of this study was to assess the longterm efficacy, safety, and tolerability of risperidone, over a cumulative period of 3 years, in treating children with disruptive behaviour disorders and below average intelligence (IQ 35-84). This trial included 35 children (aged 6-16 years), diagnosed with disruptive behaviour disorder. All subjects had previously completed a 1-year, open-label risperidone study, and this extension study followed them for an additional 2 years of treatment. Safety was assessed using the Extrapyramidal Symptom Rating Scale (ESRS), clinical laboratory tests, electrocardiograms, and the recording of adverse events, vital signs, Tanner score, and changes in body mass index (BMI). Efficacy was measured using the Clinical Global Impression of Severity (CGI-S) scale. The beneficial effects observed in the original trial were maintained during the extension. Few extrapyramidal side-effects occurred, as assessed by the ESRS, and there were no cases of tardive dyskinesia. The children showed a modest increase in BMI, part of which may be attributed to normal growth over the 2-year period. Most adverse events were mild or moderate in severity, and none of them were considered probably or very likely related to risperidone. Continuing low-dose risperidone for up to 3 years appears to be safe and effective in children with disruptive behaviour disorders.

The development of resistance in different inbred strains of mice to infection with Nematospiroides dubius. Infection by the intestinal nematode parasite Nematospiroides dubius was studied in seven different inbred mouse strains. Although there was some minor variation in the susceptibility of the different strains to a primary infection there were marked differences in their ability to develop resistance to infection following repeated exposure to infective larvae. The strains of mice which developed the best resistance also expelled adult worms arising from the previous infections. The adult worms resulting from a primary infection were slowly eliminated in two inbred strains studied whereas no loss occurred from outbred LACA mice. Although males and females of two strains, C3H/HeJ and CBA/H were equally susceptible to a primary infection, the females developed better resistance than the male mice following two oral administrations of third stage larvae. Infected mice of every strain and both sexes contained high levels of IgG1 in the serum.

Vancomycin-resistant enterococci: an emerging health problem. Since 1995, KePRO has worked with the peer review organization for 13 other states/commonwealths and the District of Columbia, as well as the Boston Regional Office of the Health Care Financing Administration, in the implementation of the largest study ever conducted involving Vancomycin-resistant enterococci (VRE). Fifteen Pennsylvania hospitals volunteered to participate in the study, designed to identify and assess the appropriateness of vancomycin use, contributing 19 percent of the total records used in the baseline study. This article, the first of two, describes VRE and its increasing prevalence. In the second installment, we will describe patterns of vancomycin use identified in KePRO's study of participating Pennsylvania hospitals, as well as the steps these hospitals are taking to control antibiotic use. Since all data gathered by KePRO are protected by federal confidentiality guidelines, the facilities that graciously agreed to pioneer KePRO's vancomycin utilization project will not be identified or identifiable.

[Distal renal tubular dysfunction in seriously undernourished pediatric patients]. Seriously undernourished patients have a bigger tendency to metabolic acidosis than euthrophic individuals. The objective of the present work was to realize a study of the renal tubular function in 30 severely undernourished children. The investigation was a prospective, descriptive and transversal study. A test of overload with 5% sodium bicarbonate was realized to 30 seriously undernourished children whose primari etiology was marasmus, kwashiorkor or with mixed conditions, with ages of 6 months to 5 years, from both sexes, hemodynamically stable, with metabolic acidosis, hiperchloremia and positive urinary anion gap. The relation calcium/creatinine and the index uric acid/creatinine were determined. The absolute and relatives frequencies, average values and standard deviations were calculated. Infants represented 80% of the evaluated patients. The clinical forms kwashiorkor and mixed forms, of chronic evolution prevailed. Distal tubular renal acidosis was observed in 12 patients (40%) after the test overload with 5% bicarbonate. The average values of the relation calcium/creatinine of children <2 years was 0.362 +/- 0.414 and of children >2 years was 0.265 +/- 0.222. The uric acid/creatinine index was 0.57 +/- 0.28. Metabolic acidosis is frequent in serious infantile undernourishment, which, according to the results observed, obeys to distal renal tubular dysfunction. The interpretation of the relation calcium/creatinine and the uric acid/creatinine index is difficult, becoming necessary to increase the investigations in these patients.

Endometrial changes after long-term use of continuous oestrogen and cyclic progestogen. Eight women with primary failure of ovarian function and twelve women undergoing the climacteric were treated sequentially with oestradiol-oestriol and norethisterone acetate (Trisequens and Trisequens Forte, Novo). After a mean treatment period of 5 yr (range 3-8 yr) endometrial biopsies were taken on day 11 or 12 at the end of an oestrogen-only phase. All biopsies showed the presence of a proliferative endometrium without any signs of hyperplasia or carcinoma in situ. Although cyclic oestrogen therapy can cause hyperplasia, a small dose of a progestogen (norethisterone acetate 1 mg) for 10 days in a 28-day cycle can prevent hyperplasia of the endometrium during long-term treatment.

Expression of a single gene encoding microbody NAD-malate dehydrogenase during glyoxysome and peroxisome development in cucumber. A full-length cDNA clone encoding microbody NAD(+)-dependent malate dehydrogenase (MDH) of cucumber has been isolated. The deduced amino acid sequence is 97% identical to glyoxysomal MDH (gMDH) of watermelon, including the amino terminal putative transit peptide. The cucumber genome contains only a single copy of this gene. Expression of this mdh gene increases dramatically in cotyledons during the few days immediately following seed imbibition, in parallel with genes encoding isocitrate lyase (ICL) and malate synthase (MS), two glyoxylate cycle enzymes. The level of MDH, ICL and MS mRNAs then declines, but then MDH mRNA increases again together with that of peroxisomal NAD(+)-dependent hydroxypyruvate reductase (HPR). The mdh gene is also expressed during cotyledon senescence, together with hpr, icl and ms genes. These results indicate that a single gene encodes MDH which functions in both glyoxysomes and peroxisomes. In contrast to icl and ms genes, expression of the mdh gene is not activated by incubating detached green cotyledons in the dark, nor is it affected by exogenous sucrose in the incubation medium. The function of this microbody MDH and the regulation of its synthesis are discussed.

Sphenoid sinus chondromyxoid fibroma mimicking a mucocele. We report the case of a 44-year-old man who presented with a chondromyxoid fibroma (CMF) of the sphenoid sinus, which filled the sinus and clinically and radiologically resembled a mucocele. Chondromyxoid fibromas are the least common cartilaginous neoplasms of bone, typically occurring in the metaphysis of long bones. They have occasionally been described in the facial bones, usually the mandible and maxilla, and rarely involve the paranasal sinuses. Chondromyxoid fibroma displays a relatively unique histological appearance, with characteristic lobulation, with spindle to stellate cells embedded in a myxoid or chondroid matrix. The periphery of the lobules tends to be more cellular than the center. Despite having been described nearly 60 years ago, the histogenesis of CMF remains controversial. Although CMFs are generally regarded as benign neoplasms, they may show an infiltrative pattern and may recur, particularly when they are in locations where complete surgical excision may be difficult or impossible.

Predictors of survival in patients bridged to transplantation with the thoratec VAD device: a single-center retrospective study on more than 100 patients. Careful patient selection markedly influences the outcome of patients who undergo mechanical circulatory support. Therefore, we tried to evaluate predictors of survival after implantation of the Thoratec ventricular assist device (VAD). Between October 1992 and January 2000, 104 patients (86 men, 18 women, aged 11 to 69 years) received the Thoratec VAD as a bridge to transplant. A total of 51 patients required left ventricular support (LVAD), 50 patients required biventricular support (BVAD), and 3 patients required total artificial heart implantation. We performed univariate analysis of 25 parameters with regard to their effect on survival and then applied a multivariate analysis to evaluate those factors that turned out to be marginally significant. We performed all analysis for the total collective as well as for the LVAD and BVAD sub-group. The BVAD patients tended to have worse outcomes than did LVAD patients. We found no significant predictors of survival in either sub-group. In the total collective, however, we found the following pre-implant conditions were independent risk factors for survival after VAD implantation: patient age > 60 years (odds ratio [OR] 3.87, confidence interval [CI] 1.39 to 10.76), pre-implant ventilation (OR, 6.76; CI 2.42 to 18.84), and increased pre-implant total bilirubin (OR, 1.42; CL, 1.19 to 1.69). Transplant candidates on inotropic support should be considered for bridging to transplant as soon as bilirubin values start to increase or before respiratory function deteriorates and ventilation becomes necessary. In elderly patients, careful patient selection, particularly considering potential risk factors, might favorably affect their outcomes.

Carbachol induces oscillations of membrane potassium conductance in a colonic cell line, T84. Effects of carbachol on membrane potential and current in T84 cells were determined using whole cell patch-clamp techniques. When the pipettes contained a standard KCl solution and the bath contained a standard NaCl solution, carbachol (100 microM) caused a rapid hyperpolarization to the K+ equilibrium potential (EK+), followed by potential oscillations. When membrane potential was clamped to 0 mV, carbachol induced an outwardly directed K+ current in 31 of 37 cells, with a peak value of 618 +/- 51 (SE) pA. In 77% of these cells the current oscillated and gradually declined to base line. Atropine (20 microM) blocked this response. In symmetric KCl solutions the carbachol-induced current reversed at 0 mV with no rectification. Ba2+ or Cs+ did not block the current, but tetraethylammonium ion (TEA) reduced the number of responding cells. Although a Cl- conductance was found in resting cells, carbachol did not cause an increase in Cl- current when the cells were voltage-clamped to EK+, or when voltage-clamped to +/- 60 mV while bathed in symmetric NaCl solutions. When the Ca2(+)-buffering capacity of the pipette solution was increased, 80% of the cells responded to carbachol, but only 10% oscillated; however, no K+ current was induced by carbachol when the pipette was made nominally Ca2+ free. The current was not affected by removal of Ca2+ from the bath. These results show that carbachol induces an oscillating Ca2(+)-activated K+ conductance in T84 cells, but no Cl- conductance. This K+ conductance is dependent on the mechanisms that regulate intracellular Ca2+.

[Epidemiology of drug use during the first three months of life in a urban area of southern Brazil]. The few studies on the use of medicines in children point to excessive use, and in these studies, physicians are those mainly responsible for the prescription of medicines. In order to get to know the patterns of consumption medicines better, a study was made in children in their first three months of life, according to social biological, food pattern and use of health services of variables. The patterns of the use of medicines during the first three months of life in 655 urban children born in Pelotas, Brazil, in 1993, were described. Information on the use of medicines was collected during a two-week period in the first and third month of life. The use of medicines was reported by 65% of mothers at the 1st and 69% at the 3rd month of life. Seventeen per cent of children consumed three or more different medicines during those periods. Fixed combinations of three or more components-which was taken as an indicator of the poor of medicines quality-were consumed by 14% of the children at the 1st and 19% at the 3rd months of life. At the latter age, 20% of children had used a given medicine for one month or more. At the first month follow-up, Benzalkonium Chloride + Normal Saline Solution (nasal drops), Nystatin Mixture and Dimethicone + Homotropine were the most frequently used medicines. At the third month they were, Aspirin, Benzalkonium Chloride + Normal Saline Solution and Dimethicone + Homatropine. The main reasons for taking medicines were cramps at the first month and colds at the third. At the first month follow-up, children with three or more siblings used 64% less medicines than the older ones. Children who were not breast-fed at the end of the first month showed a 75% greater risk of use of medicines. Similar results were observed at the third month follow-up. Some of the medicines used were not recommendable for children. Since early age children are submitted to an intense use of medicines for almost every conceivable reason, with the risk of potential side-effects and the possible lead to medicine or other drugs addiction.

Soil bacterium Pseudomonas sp.: destroyer of mustard gas hydrolysis products. A bacterial culture capable of utilizing products of mustard gas hydrolysis as a source of carbon was isolated from soil. This culture was tolerant to organochlorine substances in the hydrolysate. The bacterium was identified as Pseudomonas sp. The bacterium utilizes the major product of mustard gas hydrolysis, thiodiglycol, through two pathways. One involves the oxidation of the primary alcoholic groups in thiodiglycol, yielding thiodiglycolic and thioglycolic acids. The cleavage of the C-S bonds in these acids gives rise to acetate, which is then used further in the cell metabolism. The other pathway involves the cleavage of the C-S bond in the thiodiglycol molecule, yielding beta-mercaptoethanol, which is transformed by Pseudomonas sp. into thioglycolic acid. The results show the promise of this bacterium for the bioremediation of mustard gas-contaminated soils.

[A case of unresectable rectal cancer with liver and pulmonary metastases that responded remarkably to pharmacokinetic modulating chemotherapy]. We treated a patient with unresectable rectal cancer with multiple liver, pulmonary and lymph node metastases that responded remarkably to pharmacokinetic modulating chemotherapy (PMC). The patient was a 63-year-old male. Colonoscopy showed a type 3 advanced lower rectal cancer. Examinations by computed tomography and chest X-ray revealed unresectable rectal cancer invading the sacrum and bladder with multiple liver and pulmonary metastases and swollen para-aortic lymph nodes. The patient was treated by colostomy and postoperative PMC. UFT (400 mg/day) was orally administered daily and a continuous infusion of 5-FU (1,000 mg/24 h) was given once a week. After 10 courses of treatment with PMC, the primary lesion was remarkably reduced. This chemotherapy also produced partial responses in the pulmonary metastases and para-aortic lymph node swelling. The patient experienced few side effects and had good QOL in the terminal stage. This chemotherapy regimen appears to be an effective and promising therapy with few side effects, even for patients with unresectable advanced colorectal cancer.

Membrane-bound tubulin in brain and thyroid tissue. Brain and thyroid tissue contain membrane-bound colchicine-binding activity that is not due to contamination by loosely bound cytoplasmic tubulin. This activity can be solubilized to the extent of 80 to 90% by treatment with 0.2% Nonidet P-40 with retention of colchicine binding. Extracts so obtained contain a prominent protein band in disc gel electrophoresis that co-migrates with tubulin. Membranes, and the solubilized protein therefrom, exhibit ligand binding properties like tubulin; for colchicine the KA is approximately 1 X 10(6) M-1 in brain and approximately 0.6 X 10(6) M-1 in thyroid; for vinblastine the KA is approximately 8 X 10(6) M-1 for both tissues; and for podophyllotoxin the Ki is approximately 2 X 10(-6) M for both tissues. Displacement by analogues of colchicine is of the same order as for soluble tubulin. Although membrane-bound colchicine-binding activity shows greater thermal stability and a higher optimum binding temperature (54 degrees versus 37 degrees) than soluble tubulin, this appears to be the result of the membrane environment since the solubilized binding activity behaves like the soluble tubulin. Antibody against soluble brain tubulin reacts with membranes and solubulized colchicine-binding activity from both brain and thyroid gland. We conclude that brain and thyroid membrane preparations contain firmly bound tubulin or a very similar protein.

The dprA gene is required for natural transformation of Helicobacter pylori. Genetic recombination in Helicobacter pylori is believed to be involved in host adaptation of this gastric pathogen and uptake of DNA by natural transformation can result in changes in virulence factors as well as antigenic variation. To elucidate the mechanisms involved in natural transformation we tested two genes with homology to known competence genes (dprA and traG) for their role in this process. Insertion mutants in these genes were constructed in two different H. pylori strains and their competence by natural transformation was compared to the wild-type. Mutation of the traG homolog did not reduce competence. Mutation of the dprA gene, however, severely impaired natural transformation both with plasmid and chromosomal DNA. Our data indicate that dprA and comB3 are essential parts of a common pathway for chromosomal and plasmid transformation.

In vitro and in vivo Anticancer Effects of a Novel 9-Phenyldibenzo[a,c]phenazin-9-ium Cation and Its Ligands. Multidrug resistance (MDR) is a major problem in cancer treatment. Cu complexes possess the ability to overcome MDR in cancer. Therefore, the search for new Cu complexes is of great clinical significance and we address the anticancer effects of a previously synthesized novel 9-phenyldibenzo[a,c]phenazin-9-ium cation [1(+)] as [1] [CuCl2] and as [1] [I]. The existence of the monovalent Cu(I) in [1] [CuCl2] was proven by electron paramagnetic resonance (EPR) studies and in vivo anticancer effects were studied in animals. The monovalent nature of the Cu ion in [1] [CuCl2] was determined through EPR. The mean survival time of mice bearing doxorubicin-resistant Ehrlich ascites carcinoma cells is longer when [1] [I] is injected intraperitoneally whereas [1] [CuCl2] does not significantly increase the median survival in tumor-bearing mice. Compounds do not follow the immunomodulatory route and only [1] [I] shows cytotoxic activity in both MDR and drug-sensitive leukemia cell lines. An organic iodide complex rather than a cupric complex possesses direct cytotoxic potential.

Stochastic models for subpopulation emergence in heterogeneous tumors. A stochastic analog to a deterministic model describing subpopulation emergence in heterogeneous tumors is developed. The resulting system is described by the Fokker-Planck or forward Kolmogorov equation. A finite element approach for the numerical solution to this equation is described. Four biological and clinical scenarios are simulated (emergence of heterogeneity, exclusion of a subpopulation, and induction of drug resistance in both pure and heterogeneous tumors). The results of the simulations show that the stochastic model describes the same basic dynamics as its deterministic counterpart via a convective component, but that for each simulation a distribution of tumor sizes and mixes can also be derived from a diffusive component in the model. These distributions yield estimates for subpopulation extinction probabilities. The biological and clinical relevance of these results are discussed.

A compact 3D-printed interface for coupling open digital microchips with Venturi easy ambient sonic-spray ionization mass spectrometry. Digital microfluidics (DMF) based on the electrowetting-on-dielectric phenomenon is a convenient way of handling microlitre-volume aliquots of solutions prior to analysis. Although it was shown to be compatible with on-line mass spectrometric detection, due to numerous technical obstacles, the implementation of DMF in conjunction with MS is still beyond the reach of many analytical laboratories. Here we present a facile method for coupling open DMF microchips to mass spectrometers using Venturi easy ambient sonic-spray ionization operated at atmospheric pressure. The proposed interface comprises a 3D-printed body that can easily be "clipped" at the inlet of a standard mass spectrometer. The accessory features all the necessary connections for an open-architecture DMF microchip with T-shaped electrode arrangement, thermostatting of the microchip, purification of air (to prevent accidental contamination of the microchip), a Venturi pump, and two microfluidic pumps to facilitate transfer of samples and reagents onto the microchip. The system also incorporates a touch-screen panel and remote control for user-friendly operation. It is based on the use of popular open-source electronic modules, and can readily be assembled at low expense.

[microRNA and diabetes: tiny things causing huge effects]. Soon after their discovery microRNA (miRNA) emerged as central natural regulators of gene expression. Although the complex mechanisms of action and impact of miRNA on development, physiology and disease are still elusive, significant progress has been made in deciphering the roles of some miRNA in insulin secretion and action. Here we examine the close relationship existing between miRNA and glucose metabolism as well as their putative role in the pathogenesis of diabetes and their possible utility as biomarkers of this disease.

Primary melanoma of the ovary in a 25 year old primigravida--a case report. A 25 year old primigravida with edema of the left foot and fetal distress during 36 weeks gestational period underwent an emergency lower segment cesarian section (LSCS). During surgery ascites and a left ovarian tumor with omental seedlings were observed. Cytopathology of the ascitic fluid, histopathology of the ovarian tumor and the omental seedlings showed features of a malignant melanoma, further confirmed at electron microscopy. Considering the age of the patient and the intra-abdominal restriction of metastasis of the neoplasms this tumor appeared to be a primary melanoma of the ovary. This case is reported since there is no reference to a pure melanoma of the ovary occurring in a young primigravida in the literature.