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Emission tomography in femoral neck fracture for evaluation of avascular necrosis. Two cases of operated femoral neck fractures are presented, in whom an intact femoral head isotope uptake was found with conventional Tc-MDP scintimetry. In both patients, emission tomography using the rotating slant-hole technique was diagnostic.

[Immunotherapy in lung cancer: checkpoint inhibitors]. Monoclonal antibodies against the PD-1 receptor or its ligands result in a recovery of T cell responses against tumor antigens. Nivolumab is the first antibody that has been approved in lung cancer. This mode of action is very intersting, especially because of long term responses and the moderate toxicity.

[Medical treatment of calcium nephrolithiasis (author's transl)]. Calcium calculi are by far the most frequent of urinary stones. In many cases their formation is enhanced by lithogenetic abnormalities, including idiopathic calciuria. The basis of the treatment is to promote diuresis by absorbing for an indefinite period a mineral water containing less than 100 mg/l of calcium. There is no evidence that drugs reducing calciuria (thiazides, phosphorus) or uraturia (allopurinol) are effective, and they should be reserved to cases of rapidly progressive lithiasis. A long-term strategy for the prevention of lithiasis is discussed.

Diagnostic confidence of sonoelastography as adjunct to greyscale ultrasonography in lateral elbow tendinopathy. Conventional ultrasonography or magnetic resonance (MR) imaging is commonly performed to obtain information about the severity of the disease, location of the injury, and differential diagnosis. The aim of this research was to investigate the diagnostic confidence of sonoelastography as an adjunct to greyscale ultrasonography in lateral elbow tendinopathy. A single experienced physiatrist performed greyscale ultrasonography and sonoelastography in 28 patients (9 men, 19 women; mean age, 48.5 years; age range, 36-67 years) with unilateral symptoms of lateral elbow tendinopathy; the asymptomatic elbows were used as controls. Greyscale images were described as normal, tendinosis, partial-thickness tear, and full-thickness tear. Sonoelastographic images of the common extensor tendon were analyzed qualitatively (scoring of the elastic spectrum) and quantitatively (based on a color histogram). Both the imaging methods had high sensitivity, specificity, and accuracy for diagnosing lateral elbow tendinopathy. Considering the clinical diagnosis of lateral elbow tendinopathy, sonoelastography showed significantly higher diagnostic accuracy (96.4%) than ultrasonography (89.5%, P < 0.01). Quantitative analysis showed objective interpretation of the sonoelastographic images that revealed greater intensity of green and blue pixels in symptomatic elbows (P < 0.01). Sonoelastography increases diagnostic confidence in tennis elbow pathology over greyscale ultrasonography alone and may be an additional powerful diagnostic tool in cases of lateral elbow tendinopathy with inconclusive greyscale ultrasonographic findings.

Measurement of urinary free cortisol using liquid chromatography-tandem mass spectrometry: comparison with the urine adapted ACS:180 serum cortisol chemiluminescent immunoassay and development of a new reference range. The measurement of urinary free cortisol (UFC) is commonly used in the investigation of possible Cushing's syndrome. With the recent availability of liquid chromatography-tandem mass spectrometry (LC-MS/MS) in hospital laboratories, we wanted to develop a specific UFC LC-MS/MS method and compare it with our current immunoassay method and develop a new LC-MS/MS reference range if required. A UFC LC-MS/MS method using deuterated cortisol as an internal standard was optimized using solid-phase extraction as a clean-up procedure. The multiple reaction-monitoring transitions used for the detection of cortisol and deuterated cortisol were 363.1 > 121 and 365.1 > 121.8, respectively. The method was investigated regarding precision, linearity, sensitivity, recovery and interference. UFC was measured by the in-house urine adapted ACS:180 serum cortisol immunoassay and the developed LC-MS/MS method in 110 urine samples from patients being investigated for possible Cushing's syndrome. The within-batch precisions (n = 25) of the LC-MS/MS method were 7.6%, 4.5% and 3.3% at 25.0 nmol/L, 49.6 nmol/L and 344.6 nmol/L, respectively; the between-batch precisions (n = 10) were 9.4%, 9.4% and 8.4%, respectively, at these concentrations. The method is sensitive down to 5 nmol/L and linear up to at least 1000 nmol/L. The method showed adequate cortisol recovery and no interference from the numerous drugs and steroids tested. The total run time for 20 samples, including sample preparation, was 120 min. A scatter plot of paired UFC measurements on the LC-MS/MS and the ACS:180 gave the equation: LC-MS/MS = 0.408 (ACS:180) + 2.65, r2 = 0.6664. The 24-h measured UFC results on 110 samples (25 men and 85 women) were positively skewed. After log transformation the data were less skewed, and following back transformation of the lower 97.5th centile, the upper limit of normal was 165 nmol/24 h. The 95th centile of the untransformed data was 146 nmol/24 h (n = 110, 25 men and 85 women). Separated by sex, the 95th centile was 152 nmol/24 h for men (n = 25) and 141 nmol/24 h for women (n = 85). We have developed a UFC LC-MS/MS method with a solid-phase extraction clean-up step. The method shows adequate performance and is suitable for routine laboratory use. The mixed sex (n = 110, men = 25, women = 85) reference range was up to 165 nmol/24 h or 146 nmol/24 h, depending on how the data are manipulated.

A discriminative kernel-based approach to rank images from text queries. This paper introduces a discriminative model for the retrieval of images from text queries. Our approach formalizes the retrieval task as a ranking problem, and introduces a learning procedure optimizing a criterion related to the ranking performance. The proposed model hence addresses the retrieval problem directly and does not rely on an intermediate image annotation task, which contrasts with previous research. Moreover, our learning procedure builds upon recent work on the online learning of kernel-based classifiers. This yields an efficient, scalable algorithm, which can benefit from recent kernels developed for image comparison. The experiments performed over stock photography data show the advantage of our discriminative ranking approach over state-of-the-art alternatives (e.g. our model yields 26.3% average precision over the Corel dataset, which should be compared to 22.0%, for the best alternative model evaluated). Further analysis of the results shows that our model is especially advantageous over difficult queries such as queries with few relevant pictures or multiple-word queries.

A facile method to synthesize strong salt-enhanced hydrogels based on reversible physical interaction. To overcome the adverse effects of salt on the mechanical properties of hydrogels, a facile double cross-linking method has been proposed to synthesize salt-enhanced tough hydrogels. Herein, a poly(hexafluorobutyl methacrylate-acrylamide) hydrogel [P(AAm-co-HFBMA) hydrogel] is prepared by the copolymerization of acrylamide (AAm) and hexafluorobutyl methacrylate (HFBMA) with N,N'-methylene bisacrylamide (NMBA) as a cross-linking agent in a dimethylformamide (DMF)/aqueous solution; DMF is then replaced by water. The results indicate that the tensile fracture stress of the P(AAm-co-HFBMA) hydrogel (20 mol% HFBMA) is as high as 0.43 MPa, which is far better than that of the PAAm hydrogel (ca. 30 kPa). Additionally, with a further increase in the hydrophobic structural units (25 mol% HFBMA), the tensile fracture stress of the P(AAm-co-HFBMA) hydrogel can be increased up to 2.34 MPa. The mechanical strength of the P(AAm-co-HFBMA) hydrogel is significantly enhanced to 3.50 MPa (2 M) from 2.34 MPa (0 M) after it is soaked in aqueous NaCl solutions with various salt concentrations. The mechanical properties and the results of the DSC analysis indicate that the main reason for its mechanical strength to exhibit a unique salt-enhancement trend can be explained as follows. After the P(AAm-co-HFBMA) hydrogel is soaked in the salt solution, the network gradually collapses with the penetration of the small molecules of salt. Thus, the hydrophobic C-F units easily form dynamic cross-linking junctions due to the switchable hydrophobic interaction between C-F groups, which can endow the P(AAm-co-HFBMA) hydrogel with a more effective dynamic energy dissipation mechanism in salt solution.

AMPA receptor development in rat telencephalon: [3H]AMPA binding and western blot studies. Telencephalic membranes from rats of different embryonic (E16, E19) and postnatal (P2, P7, P14, adult) ages were assessed for alpha-[3H]amino-3-hydroxy-5-methylisoxazole-4-propionic acid ([3H] AMPA) binding and for immunoreactivity levels of AMPA receptor subunits (GluR1, GluR2/3, and GluR4). In addition, the synaptic markers synaptophysin and NCAM140 (a neural cell adhesion molecule isoform) were examined by immunoblot. The density of [3H]AMPA binding sites increased steadily with advancing age. This increase was due mainly to the development of the large low-affinity component (KD = 400 nM) that dominates the [3H]AMPA binding profile of adult rat brain membranes. As resolved by two-site regression analysis, the high-affinity component (KD = 15 nM) of the [3H]AMPA binding increased by approximately twofold from E16 to adult, whereas the low-affinity component increased by 25-fold. Staining for GluR1 and GluR2/3 increased steadily with increasing age at all time points examined; synaptophysin and NCAM140 exhibited similar ontogenic immunostaining profiles. GluR4 immunoreactivity was first evident at P14 and increased by adulthood.(ABSTRACT TRUNCATED AT 250 WORDS)

Endoscopic stenting versus surgical bypass in advanced malignant distal bile duct obstruction: cost-effectiveness analysis. Palliative treatment of obstructive jaundice from advanced tumour of the distal bile duct is controversial. The aim of this study was to compare the clinical outcomes and costs between endoscopic stent insertion and surgery. The clinical data for 116 patients treated with either endoscopic plastic stenting (65 patients) or surgical bypass (51 patients) were reviewed and analysed. No significant difference was found between the two groups in terms of the length of hospital stay, survival time, cost, effectiveness, and early complications. However, late complications were significantly more common in the stenting group (p = 0.007). Jaundice recurred in 15 stented patients at a median time of 3 months due to stent blockage, and one surgical patient had recurrent jaundice from anastomosis stricture. Late gastric outlet obstruction occurred in one of 36 surgical patients who did not undergo prophylactic gastroenterostomy and one of 65 stented patients developed this complication. Both techniques are equally effective in biliary drainage, but stenting has a higher rate of recurrent jaundice. We recommend surgery for patients with low surgical risks and endoscopic stent in those with a short life expectancy or those unfit for surgery.

Roles of KIT and KIT LIGAND in ovarian function. Evidence from mouse mutants indicates that the Kit gene encoding KIT, a receptor present on the oocyte and theca cells, and the Mgf gene encoding KIT LIGAND, the ligand of KIT, are important regulators of oogenesis and folliculogenesis. Recently, in vitro cultures of fetal gonads, of follicles and of oocytes have identified specific targets for the KIT-KIT LIGAND interaction. In fetal gonads, an anti-apoptotic effect of KIT-KIT LIGAND interactions on primordial germ cells, oogonia and oocytes has been demonstrated. In postnatal ovaries, the initiation of follicular growth from the primordial pool and progression beyond the primary follicle stage appear to involve KIT-KIT LIGAND interactions. During early folliculogenesis, KIT together with KIT LIGAND controls oocyte growth and theca cell differentiation, and protects preantral follicles from apoptosis. Formation of an antral cavity requires a functional KIT-KIT LIGAND system. In large antral follicles, the KIT-KIT LIGAND interaction modulates the ability of the oocyte to undergo cytoplasmic maturation and helps to maximize thecal androgen output. Hence, many steps of oogenesis and folliculogenesis appear to be, at least in part, controlled by paracrine interactions between these two proteins.

Phytotoxic effects of trichothecenes on the growth and morphology of Arabidopsis thaliana. Non-volatile sesquiterpenoids, a trichothecene family of phytotoxins such as deoxynivalenol (DON) and T-2 toxin, contain numerous molecular species and are synthesized by phytopathogenic Fusarium species. Although trichothecene chemotypes might play a role in the virulence of individual Fusarium strains, the phytotoxic action of individual trichothecenes has not been systematically studied. To perform a comparative analysis of the phytotoxic action of representative trichothecenes, the growth and morphology of Arabidopsis thaliana growing on media containing these compounds was investigated. Both DON and diacetoxyscirpenol (DAS) preferentially inhibited root elongation. DON-treated roots were less organized compared with control roots. Moreover, preferential inhibition of root growth by DON was also observed in wheat plants. In addition, T-2 toxin-treated seedlings exhibited dwarfism with aberrant morphological changes (e.g. petiole shortening, curled dark-green leaves, and reduced cell size). These results imply that the phytotoxic action of trichothecenes differed among their molecular species. Cycloheximide (CHX)-treated seedlings displayed neither feature, although it is known that trichothecenes inhibit translation in eukaryotic ribosomes. Microarray analyses suggested that T-2 toxin caused a defence response, the inactivation of brassinosteroid (BR), and the generation of reactive oxygen species in Arabidopsis. This observation is in agreement with our previous reports in which trichothecenes such as T-2 toxin have an elicitor-like activity when infiltrated into the leaves of Arabidopsis. Since it has been reported that BR plays an important role in a broad range of disease resistance in tobacco and rice, inactivation of BR might affect pathogenicity during the infection of host plants by trichothecene-producing fungi.

Functional results after conservative treatment of fractures of the mandibular condyle. Since the introduction of osteosynthesis materials for rigid internal fixation after anatomical reduction there is an ongoing discussion about the treatment of condylar fractures of the mandible. Sixty patient files were analyzed and 28 patients were seen for re-examination and a x-orthopantomogram was taken. Functionality was graded with the Helkimo index at an average of 3.0 years follow-up. The clinical dysfunction index showed: severe symptoms in 11%, moderate symptoms in 39%, mild symptoms in 39% and 11% had no symptoms. Index for occlusal state showed: 21% severe occusal disturbances, 61% moderate occlusal disturbances and 18% no occlusal disturbances. According to the anamnestic dysfunction index 89% of the patients were symptom-free. The clinical outcome group showed a significant left/right ramus length difference compared with a 20-person control group. The re-examined group did not significantly differ from the control group. Conservative treatment for condylar fractures was successful in only 46% according to the 1999 consensus criteria described by Bos et al.

The use of vascularized fibula flap in mandibular reconstruction; A comprehensive systematic review and meta-analysis of the observational studies. Vascularized fibular flaps are considered the gold standard for the reconstruction of segmental defects in the mandible. This review compares the complication and success rates of these techniques between primary and secondary reconstruction, as well as between lateral and antero-lateral defects. A systematic review and meta-analysis were conducted according to PRISMA protocol and the Cochrane Handbook for Systematic Reviews of Interventions. The authors performed an independent comprehensive search using PubMed, Ovid MEDLINE, Web of Science, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov and COS Conference Papers Index according to established inclusion and exclusion criteria. The methodological index for nonrandomized studies (MINORS) was used to assess the quality of the included studies. Meta-analysis was conducted to compare the type of reconstruction and location of the defect. Seventy-eight studies, involving 2461 patients, were eligible. 83.7% of the included patient received primary reconstruction with vascularized fibular flap. The overall flap success rate was 93%. There was improvement in MINORS quality score over time with positive correlation with the publication year (r = 0.5549, P < 0.0001, CI 0.3693 to 0.6979). Meta-analysis indicated no significant association in flap success between primary and secondary reconstruction, or lateral and antero-lateral defects. Based on the available studies, this review found no evidence of difference in success or complication rates between primary and secondary reconstruction or between lateral and anterolateral defects. High-quality clinical studies are required to analyze the outcome of these techniques, especially regarding the impact of chemotherapy, radiation therapy, implant-supported dental prostheses, and preoperative planning, on the outcome of reconstruction.

T1ρ is superior to T2 mapping for the evaluation of articular cartilage denaturalization with osteoarthritis: radiological-pathological correlation after total knee arthroplasty. We compared the diagnostic performance of T1ρ and T2 mappings in the evaluation of denatured articular cartilage with osteoarthritis of the knee. 2D-Sagittal T1ρ and T2 mappings of the knee were obtained from 16 patients before total knee arthroplasty. After surgery, specimens of the femur and tibia were regionally segmented according to a 5-point scale of the severity of denaturalization. The T1ρ and T2 values in the full thickness of the articular cartilage in each region were measured by two observers. The two mappings were compared for their ability to differentiate between normal and denatured articular cartilage and also for their usefulness in grading the severity of the denaturalization using the area under receiver operating characteristic curves (Az). A p<0.05 was considered significant for each analysis. The T1ρ mapping showed a significantly higher Az value than the T2 mapping for the differentiation between normal and denatured articular cartilage (p<0.05). Regarding the assessment of the severity of denaturalization, T1ρ mapping could differentiate between normal and mild denaturalization (p<0.05), but T2 mapping could not. However, there were no significant differences between the two mappings in the discrimination of mild versus moderate denaturalization or of moderate versus severe denaturalization. The two observers showed good agreement in the results (intraclass correlation coefficient=0.81 for T1ρ and 0.92 for T2). T1ρ mapping is superior to T2 mapping for the evaluation of denatured articular cartilage with osteoarthritis of the knee.

Robust procedures for analysing a two-period cross-over design with baseline measurements. Patel analysed a two-period cross-over design with baseline measurements assuming bivariate normality for the joint distribution of the period responses. In this paper, we propose non-parametric methods for analysing this design, including the use of the Wilcoxon rank sum test to derive the preliminary tests from the baseline measurements. We fit a robust regression line of the treatment response on baseline for each period and compute residuals. We also fit a robust locally weighted regression as an alternative method for computing residuals. Then, following Koch's procedure, we analyse the residuals for testing the significance of the treatment x period interaction and the treatment difference. We provide a numerical example to illustrate the methods.

No more surprising than a broken pitcher? Maternal and child health in the early years of the Pan American Sanitary Bureau. The priorities and activities of international health organizations have historically been determined at the metropolitan level or through a confluence of central and local interests. The case of maternal and child health and the Pan American Sanitary Bureau during the first half of the 20th century demonstrates a different phenomenon. Rather than sparking interest and actions in maternal and child health in Latin America, the PASB ignored this area even though the agency was repeatedly urged by numerous countries in the region over several decades to provide support. This article begins with an examination of the emergence of maternal and child health circa 1900 in Europe, North America, and Latin America, identifying political, demographic, ideological, economic, and cultural commonalities and differences in these regions. We then turn to the PASB's early history and modus operandi, the pressure exerted by Latin American countries upon the PASB to pay attention to maternal and child health, and the Bureau's unwillingness to work in this area. Next we explore concomitant developments in maternal and child health and eugenics within Latin America in the 1920s and 1930s and the PASB's first steps in this area. Finally we discuss the conflict over the PASB's role in maternal and child health on several dimensions: as a manifestation of differing cultural priorities in the U.S. and Latin America; as a question of struggle for organizational power within the PASB; and as part of a richer understanding of the diffusion of early 20th-century public health and medical practices.

Feasibility and validity of a computer administered version of SEIQoL-DW. Computer administrered QoL instruments are increasingly used to assess outcomes. Our aim was to assess the feasibility and validity of an electronic version of the SEIQoL-DW. Pharmacy students (n = 40; mean age 25; 92% women) were administrated both the touch screen and the paper-and-pen versions in a cross-over study. The majority of the students (65 %) preferred the computer version, while almost a third (27%) preferred the paper and pen version. There was no overall order effect and the SEOQoL-DW index mean scores differed with 1.2 between the two versions. Those respondents completing the computer version first had higher scores than those completing the computer version second. The ICC comparing the formats was 0.77 (CI: 0.57-0.88) and the limits of agreement method showed that 85% of the observations were within +/- 1-10 units. Most students (82%) judged their QoL as being equivalent to their SEIQoL-DW score. The computer version of the SEIQoL-DW seems to be feasible and acceptable and seems to be valid alternative to the paper and pen version. However, further validation studies in larger patient populations are needed.

Optimisation and validation of a capillary electrophoresis method for the simultaneous determination of diazepam and otilonium bromide. A simultaneous assay of diazepam and otilonium bromide in coated tablets by capillary zone electrophoresis (CZE) was developed. The influence of various parameters (voltage, temperature, buffer concentration and pH, ethanol percentage) on analysis time and on the theoretical plates of the two peaks was investigated by means of experimental design. A response surface study was carried out by means of a 27-run D-optimal matrix. The best background electrolyte was found to be 0.13 M, pH 2.9 Britton-Robinson buffer, containing 10% v/v ethanol. Other optimised parameters were voltage (30 kV) and temperature (30 degrees C). The UV detector for quantitation of otilonium bromide and diazepam was set at 280 nm and 230 nm, respectively. Procaine hydrochloride was used as internal standard and run time was less than five minutes. Validation was performed, for drug substance and drug product, according to ICH3 guidelines. For drug product the recovery for otilonium bromide and diazepam ranged from 98.3% to 101.2% and from 97.1% to 99.0%, respectively; the RSD values found for otilonium bromide and diazepam ranged from 2.4% to 3.0% and from 1.1% to 4.5%, respectively.

[A new method of evaluation of split renal function based on contrast-enhanced multislice spiral computed tomography]. Traditionally, evaluation of the split renal function is performed using nephroscintigraphy. However, as shown in several studies, there might be quite significant inaccuracy in the interpretation of dynamic nephroscintigraphy results. But due to the lack of alternative methods for evaluation of split renal function, nephroscintigraphy remains the method of choice. To investigate the feasibility of digital analysis of contrast-enhanced MSCT imaging for evaluation of the split renal function. This is a prospective study conducted at the R.M. Fronshteyn Clinic of Urology from November 2015 to February 2017. The study comprised 31 patients with urolithiasis (n=7), hydronephrosis (n=9), kidney cancer (n=14) and urinary bladder tumor (n=1). During the preoperative period, the patients underwent contrast-enhanced MSCT, 3D-reconstruction, and digital analysis. The obtained data were compared with the results of dynamic nephroscintigraphy. Contrast-enhanced MSCT findings were not inferior to data obtained with dynamic nephroscintigraphy regarding information content (p<0.004). The new method of digital processing of three-dimensional contrast-enhanced MSCT allows for concomitant assessment of both the anatomical features of the kidney and renal function that may help to improve the accuracy of surgical planning to choose the optimal extension of the intervention.

Manganese carbonyl fluorides: are they viable molecules? The mononuclear Mn(CO)(5)X and binuclear Mn(2)(CO)(8)(μ-X)(2) manganese carbonyl halides have long been known for the halogens Cl, Br, and I. However, the corresponding manganese carbonyl fluorides (X = F) remain unknown. The structures and thermochemistry of such manganese carbonyl fluorides and their decarbonylation products have now been investigated using density functional theory. In all cases singlet structures were found to have lower energies than the corresponding triplet structures. The expected octahedral structure is predicted for Mn(CO)(5)F. Decarbonylation of Mn(CO)(5)F is predicted to give trigonal bipyramidal Mn(CO)(4)F with equatorial fluorine. Further, decarbonylation gives tetrahedral Mn(CO)(3)F. All of the binuclear Mn(2)(CO)(n)F(2) structures (n = 8, 7, 6) are predicted to have a central Mn(2)F(2) unit with two bridging F atoms, a non-bonding Mn···Mn distance of ~3.1 Å, and exclusively terminal CO groups. The thermochemistry of these manganese carbonyl fluorides indicates that they are viable species. This suggests that the failure to date to synthesize the simple manganese carbonyl fluorides arises from a lack of a suitable synthetic method rather than from the instability of the desired products.

Thermal compatibility of titanium-porcelain system. Porcelain-fused-to metal systems are popular in restorative dentistry. Residual stress caused by a mismatch of the thermal expansion coefficient of metal and porcelain induce clinical failure of the restoration. Titanium and its alloys have been gradually used in dentistry for their adequate strength, good corrosion resistance and excellent biocompatibility. Their oxidation characteristics and low thermal expansion coefficients capacitate for matching the low fusing porcelains. This investigation examined thermal compatibility of pure titanium with two low fusing porcelains and one high fusing porcelain. Thermal expansion coefficients (alpha) of pure titanium and porcelains were measured from room temperature to 600 degrees C at a mean heating rate of 5 degrees C/min. Difference in thermal expansion values (delta alpha) was also calculated to present the residual stress in each titanium-porcelain pairs. The bonding patterns of titanium to each opaque was demonstrated similar results from the predictions of alpha and delta alpha values.

Osteoarthritis and stem cell therapy in humans: a systematic review. Osteoarthritis (OA) is a leading cause of disability in the world. Mesenchymal stem cells (MSCs) have been studied to treat OA. This review was performed to systematically assess the quality of literature and compare the procedural specifics surrounding MSC therapy for osteoarthritis. PubMed, CINAHL, EMBASE and Cochrane Central Register of Controlled Trials were searched for studies using MSCs for OA treatment (final search December 2017). Outcomes of interest included study evidence level, patient demographics, MSC protocol, treatment results and adverse events. Level I and II evidence articles were further analyzed. Sixty-one of 3,172 articles were identified. These studies treated 2,390 patients with osteoarthritis. Most used adipose-derived stem cells (ADSCs) (n = 29) or bone marrow-derived stem cells (BMSCs) (n = 30) though the preparation varied within group. 57% of the sixty-one studies were level IV evidence, leaving five level I and nine level II studies containing 288 patients to be further analyzed. Eight studies used BMSCs, five ADSCs and one peripheral blood stem cells (PBSCs). The risk of bias in these studies showed five level I studies at low risk with seven level II at moderate and two at high risk. While studies support the notion that MSC therapy has a positive effect on OA patients, there is limited high quality evidence and long-term follow-up. The present study summarizes the specifics of high level evidence studies and identifies a lack of consistency, including a diversity of MSC preparations, and thus a lack of reproducibility amongst these articles' methods.

Aerobic hydrogenase activity in Anacystis nidulans. The oxyhydrogen reaction. 1. The oxyhydrogen reaction of Anacystis nidulans was studied manometrically and polarographically in whole cells and in cell-free preparations; the activity was found to be associated with the particulate fraction. 2. Besides O2, the isolated membranes reduced artificial electron acceptors of positive redox potential; the reactions were unaffected by O2 levels less than 10--15%; aerobically the artificial acceptors were reduced simultaneously with O2. 3. H2-supported O2 uptake was inhibited by CO, KCN and 2-n-heptyl-8-hydroxyquinoline-N-oxide. Inhibition by CO was partly reversed by strong light. Uncouplers stimulated the oxyhydrogen reaction. 4. The kinetic properties of O2 uptake by isolated membranes were the same in presence of H2 and of other respiratory substrates. 5. Low rates of H2 evolution by the membrane preparations were found in presence of dithionite; methyl viologen stimulated the reaction. 6. The results indicate that under certain growth conditions Anacystis synthesizes a membrane-bound hydrogenase which appears to be involved in phosphorylative electron flow from H2 to O2 through the respiratory chain.

Assessment of ablative margin after radiofrequency ablation for hepatocellular carcinoma; comparison between magnetic resonance imaging with ferucarbotran and enhanced CT with iodized oil deposition. Our aim was to investigate whether magnetic resonance imaging (MRI) with ferucarbotran administered prior to radiofrequency ablation could accurately assess ablative margin when compared with enhanced computed tomography (CT) with iodized oil marking. We enrolled 27 patients with 32 hepatocellular carcinomas in which iodized oil deposits were visible throughout the nodule after transcatheter arterial chemoembolization. For these nodules, radiofrequency ablation was performed after ferucarbotran administration. We then performed T2-weighted MRI after 1 week and enhanced CT after 1 month. T2-weighted MRI demonstrated the ablative margin as a low-intensity rim. We classified the margin into three grades; margin (+): high-intensity area with a continuous low-intensity rim; margin zero: high-intensity area with a discontinuous low-intensity rim; and margin (-): high-intensity area extending beyond the low-intensity rim. In 28 (86%) of 32 nodules, there was agreement between MRI and CT. The overall agreement between for the two modalities in the assessment of ablative margin was good (κ=0.759, 95% confidence interval: 0.480-1.000, p<0.001). In four nodules, ablative margins on MRI were underestimated by one grade compared with CT. MRI using ferucarbotran is less invasive and allows earlier assessment than CT. The MRI technique performed similarly to enhanced CT with iodized oil marking in evaluating the ablative margin after radiofrequency ablation.

Heterogeneity of angiotensin action in renal circulation. Reported concentrations of angiotensin II (Ang II) in renal interstitial fluid are as high as 10 nM. Despite such high concentrations, intrarenal arterial infusion of Ang II at rates that induce far less change in renal Ang II concentration still elicits renal vasoconstriction. We examined whether the glomerular afferent arterioles (Af-Art) was more sensitive to intraluminal than extraluminal Ang II in superficial or juxtamedullary nephrons. Rat superficial Af-Arts with the intact glomerulus were microdissected and perfused in vitro at 70 mmHg, while juxtamedullary Af-Arts were visualized in isolated perfused kidneys (at 100 mm Hg) according to the method of Casellas and Navar. Increasing doses of Ang II (1 pM to 10 nM) or norepinephrine (NE; 1 nM to 1 microM) were added to either bath (extraluminal) or arteriolar perfusate (intraluminal). Decreases in luminal diameter induced by Ang II were significantly larger with intraluminal than extraluminal administration in superficial Af-Art: at 100 pM the diameter decreased by 52 +/- 8% (N = 6) and 7 +/- 3% with intraluminal and extraluminal administration, respectively. In contrast, in the juxtamedullary Af-Arts intraluminal and extraluminal Ang II caused similar constriction. On the other hand, there was no difference in intraluminal versus extraluminal NE action in either superficial or juxtamedullary nephrons. In conclusion, glomerular Af-Arts seem to have a higher sensitivity to luminal than interstitial Ang II in superficial but not juxtamedullary nephrons. Such heterogeneities in Ang II action may be important in the control of glomerular hemodynamics under various physiological and pathological conditions.

The short-term administration of Ketoprofen does not decrease the effect of Pleurodesis induced by talc or Doxycycline in rabbits. To determine whether the concomitant administration of ketoprofen, a non-steroidal anti-inflammatory drug (NSAID) has any effect on the pleurodesis induced by talc or doxycycline in rabbits. Four groups of seven New Zealand rabbits were assigned to receive the following treatments: 400mg/kg of talc intrapleurally only (group 1), 400mg/kg of talc plus 1mg/kg of ketoprofen intramuscularly (group 2), 10mg/kg of doxycycline intrapleurally only (group 3) and 10mg/kg of doxycycline plus 1mg/kg of ketoprofen intramuscularly (group 4). Intramuscular administration of ketoprofen began 4h before the intrapleural administration of the sclerosing agents, followed by twice daily administrations for 1 week. Pleural fluid was collected 24, 48 and 72h after intrapleural injections. Pleurodesis was evaluated macroscopically and microscopically after 14 days. The concomitant use of ketoprofen at 1mg/kg does not decrease the WBC, LDH, and protein in pleural fluid at 24h following intrapleural injection of talc or doxycycline. There were no significant differences in the macroscopic pleurodesis scores, the degree of microscopic pleural fibrosis, the thickness of the pleura or the percent of the pleura occupied with angiogenesis. The study shows that the short-term systemic administration of NSAIDs does not affect the efficacy of pleurodesis induced by talc or doxycycline in rabbits.

Physiological Consequences of Abdominal Aortic and Junctional Tourniquet (AAJT) Application to Control Hemorrhage in a Swine Model. Specialized tourniquets such as Abdominal Aortic and Junctional Tourniquet (AAJT) have been deployed for control of junctional hemorrhage with limited information concerning their efficacy and safety. We examined physiological effects of a 2-h abdominal application of AAJT to control groin hemorrhage in a swine model. Anesthetized pigs were subjected to 25% controlled hemorrhage and a groin arterial injury. Resulting hemorrhage from the groin wound was controlled for 2 h by applying AAJT on each pig's abdomen. After AAJT removal, the artery was repaired and blood flow was fully restored for 1 h. CT angiography and blood analyses were done and tissues collected for histology. Experiments were conducted in three groups of pigs (n = 6/group): mechanically ventilated (MV); spontaneously breathing (SB); and spontaneously breathing during AAJT application but transitioned to mechanical ventilation (SB-MV) before AAJT release. AAJT application produced sharp increases in blood pressure and heart rate. SB animals experienced labored and rapid respiration, but their PaO2 and PaCO2 were unaffected. Their respiration suddenly stopped when the AAJT was released requiring manual respiratory assistance. However, three pigs in SB group eventually died from cardiac and respiratory arrests, which coincided with hyperkalemia and metabolic acidosis that occurred after reflow. These changes were less severe in other groups. Other measures including increased hematocrit, tissue injury biomarkers, and kidney function indicators were similar in all groups. Histological changes were mild and reversible. The ischemia-induced hyperkalemia and metabolic acidosis associated with AAJT application are life-threatening in spontaneously breathing subjects. Cardiopulmonary resuscitation appears necessary when AAJT is released to prevent life-threatening consequences.

[Nuclear transfer of goat somatic cells transgenic for human lactoferrin]. Transgenic animal mammary gland bioreactors are being used to produce recombinant proteins with appropriate post-translational modifications, and nuclear transfer of transgenic somatic cells is a more powerful method to produce mammary gland bioreactor. Here we describe efficient gene transfer and nuclear transfer in goat somatic cells. Gene targeting vector pGBC2LF was constructed by cloning human lactoferrin (LF) gene cDNA into exon 2 of the milk goat beta-casein gene, and the endogenous start condon was replaced by that of human LF gene. Goat fetal fibroblasts were transfected with linearized pGBC2LF and 14 cell lines were positive according to PCR and Southern blot. The transgenic cells were used as donor cells of nuclear transfer, and some of reconstructed embryos could develop to blastocyst in vitro.

Manganese accentuates adverse mental health effects associated with alcohol use disorders. A population-based study on early neurotoxic effects of environmental exposure to manganese (Mn) enabled us to investigate the relation between blood Mn levels (MnB), alcohol consumption, and risk for alcohol use disorders (AUD) on mental health. Participants were selected using a random stratified sampling procedure. Self-administered questionnaires provided data on alcohol consumption, sociodemographics, medical history, and lifestyle. Mood states were assessed with the Brief Symptom Inventory (BSI), and risk for AUD was surveyed using a behavioral screening questionnaire and categorized into no, low, and high risk. Of 297 participants, 253 current drinkers who had responded to all questions on alcohol use were retained. Psychologic distress increased with risk for AUD and alcohol consumption > or = 420 g/week. Higher MnB levels (> or =7.5 microg/L) intensified the relation between risk for AUD and BSI scale scores. The Prevalence odd ratios for positive cases of psychologic distress with risk for AUD, 1.98 [1.13-3.46], differed when divided by MnB strata: lower MnB: 1.34 [0.64-2.85]; higher MnB: 4.22 [1.65-10.77]. These findings suggest that higher levels of blood manganese significantly increase neuropsychiatric symptoms associated with risk for alcohol use disorders.

Synthesis, structure-activity relationships and brain uptake of a novel series of benzopyran inhibitors of insulin-regulated aminopeptidase. Peptide inhibitors of insulin-regulated aminopeptidase (IRAP) enhance fear avoidance and spatial memory and accelerate spatial learning in a number of memory paradigms. Using a virtual screening approach, a series of benzopyran compounds was identified that inhibited the catalytic activity of IRAP, ultimately resulting in the identification of potent and specific inhibitors. The present study describes the medicinal chemistry campaign that led to the development of the lead candidate, 3, highlighting the key structural features considered as critical for binding. Furthermore, the in vivo pharmacokinetics and brain uptake of compounds (1 and 3) were assessed in rats and were complemented with in vitro human and rat microsomal stability studies. Following intravenous administration to rodents, 3 exhibits brain exposure, albeit it is rapidly converted to 1, a compound which also exhibits potent inhibition of IRAP.

Symptom management and psychological support for families are the cornerstones of end-of-life care for children with spinal muscular atrophy type 1. This study described end-of-life care for children affected by spinal muscular atrophy type 1 (SMA1), which is characterised by progressive muscle weakness and develops in the first six months of life. We retrospectively analysed 17 children (13 boys) who attended the University of Padua's paediatric palliative care centre in Italy from March 2000 to March 2015. All the children received supportive care without proactive respiratory intervention to prolong survival. The median age at admission was 3.57 months, and the median age at death was 6.80 months. The most frequent symptoms were dyspnoea and pain. In the last 72 hours of life, 15/17 children required more intense doses of morphine and, or, benzodiazepines for intractable dyspnoea and pain, but deep palliative sedation was not needed. Airway suction to manage secretions and nasogastric tubes was required in all cases. The place of death was previously planned by the parents in all cases - home, hospital or hospice - and 15/17 deaths occurred in that place. We also interviewed 16 of the 17 parents after their child died. Our study found that symptom management and psychological support for families were the cornerstones of end-of-life care for children with SMA1.

A comprehensive catalog of CpG islands methylated in human lung adenocarcinomas for the identification of tumor suppressor genes. CpG island methylation is an important mechanism in gene silencing and is a key epigenetic event in cancer development. As yet, the number and identities of the genes that are inactivated in cancer cells has not been determined. In order to address this issue, we have performed a comprehensive isolation of CpG islands that are methylated in human lung adenocarcinomas. We have isolated approximately 200 CpG islands that are methylated in tumor DNA including those of known tumor-associated genes such as the HOXA5 gene. As the library contains the CpG islands of a number of known tumor suppressor genes it is highly likely that additional, previously unidentified tumor suppressor genes, will be present. On average, 1-2% of CpG islands were methylated specifically in tumors although this figure differed greatly between patients. This study provides an important resource in the search for genes inactivated in tumors and for the investigation of epigenetic dysregulation of gene expression by CpG island methylation.

Polychlorinated biphenyls in farmed and wild Onchorhynchus kisutch and Onchorhynchus mykiss from the Chilean Patagonia. This paper analyses the presence of polychlorinated biphenyls (PCBs) in escaped: farmed and wild salmons in southern Chile, analysing their concentrations and congener profiles in two species (Oncorhynchus kisutch and Oncorhynchus mykiss). Muscle samples from both farmed and escaped fish of two species, O. mykiss (rainbow trout) and O. kisutch (coho salmon), were analysed for PCBs (42 congeners). To differentiate between the wild salmon and the salmon that have escaped from fish farms, the astaxanthin content in the muscular tissue was analysed with a high-performance liquid chromatography -diode array detector method. PCBs were measured by gas chromatography with an electron capture detector. The levels of astaxanthin can be used to differentiate between farmed, escaped and wild-borne salmons with statistically different concentrations. When comparing the total PCB concentrations for both trout and salmon samples, it can be determined that a separate analysis for farmed, escaped and wild-borne fish more accurately describes the real differences in the concentrations; these differences are hidden when separate analyses are not performed. The congener profiles are similar in both trout and coho salmon, where the tri-, tetra- and penta-CB congeners are the most abundant. This study is the first report of PCBs in wild-borne, farmed and escaped salmons for the Southern Hemisphere, considering that Chile is actually one of the principal world producers of salmon.

A computer program for pharmacokinetics based on maximum likelihood estimation using the gamma distribution with a probability density function: comparison with the normal distribution. A computer program is described for maximum likelihood estimation within the gamma or normal distribution which can be used to estimate pharmacokinetic parameters. Pharmacokinetic analysis using this proposed program was investigated by the Monte Carlo method. The assumed pharmacokinetic models were a one-compartment intravenous model and an oral model. The simulated drug concentrations were generated using a 10% S.D. based on the gamma or normal distribution. The gamma or normal distribution was adopted as the probability density function (p.d.f.) to estimate model parameters. The Powell method was used to maximize the logarithmic likelihood. There were no differences in the estimated parameters in terms of statistical and frequency distributions between the gamma and normal distributions using the generated data and the p.d.f. distributions. However, the number of failures to calculate the parameters using the p.d.f. with the normal distribution was more than five times that using the gamma distribution. This result suggests that it may be necessary to evaluate the validity of results computed using the maximum likelihood estimation based on a normal distribution as a data error distribution and p.d.f.

Synthesis of heterocyclic N-acetoxyarylamines and their reactivity with DNA. 2-Acetoxyamino-5-phenylpyridine and 2-acetoxyamino-3-methyl-5-phenylpyridine, being proposed ultimate carcinogens of the heterocyclic aromatic amines 2-amino-5-phenylpyridine (APP) and 2-amino-3-methyl-5-phenylpyridine (AMPP), respectively, were synthesized, crystallized and characterized. Using the 32P-postlabelling technique, we show that the total amount of adducts found in DNA after reaction with these N-acetoxyarylamines is at least 30- and 450-fold higher than in DNA reacted with equimolar amounts of the proposed proximate carcinogens 2-hydroxyamino-5-phenylpyridine and 2-hydroxyamino-3-methyl-5-phenylpyridine, respectively. These results support a postulated activation mechanism, in which N-acetoxyarylamines are the ultimate reactive species responsible for DNA modification by carcinogenic aromatic amines in vivo. The possibility to obtain the reactive 0-acetyl derivatives of APP and AMPP in crystalline form makes them unique model compounds for studies on the interaction of ultimate carcinogens of aromatic amines with DNA.

Linear and quantitative migration of stored sperm through cervical mucus during the periovular period. The ability of stored spermatozoa to penetrate fresh samples of cervical mucus obtained from 23 patients during 47 menstrual cycles was studied, utilizing an in vitro test. The determination of daily hormonal and gonadotropin values allowed an accurate realationship to be established between the results of sperm-mucus interaction and the environmental milieu. Cervical mucus was found to be effectively penetrable only on day -1 and day 0 when considered with respect to the plasma luteinizing hormone surge. Correlation was apparent between the ability of sperm to penetrate and the favorable clinical parameters of cervical assessment.

Usefulness and limits of near infrared spectroscopy monitoring during endovascular neuroradiologic procedures. Transcranial cerebral oximetry (TCCO) with near-infrared spectroscopy (NIRS) is a non-invasive, bedside technique, which allows the continuous measurement of regional cerebral oxygenation. The aim of this study was to evaluate TCCO monitoring during endovascular neuroradiologic procedures. Adult patients undergoing elective endovascular embolization of cerebral aneurysms, arteriovenous malformations, dural arteriovenous fistulas and meningiomas under general anesthesia were included in the study, over a period of 12 months. Twenty-eight procedures in 25 patients were analyzed. Regional cerebral oxygenation rSO(2) readings were significantly different according to the different phases of the neuroendovascular procedure. An effect of the underlying cerebral pathology on regional cerebral oxygenation rSO(2) recording, in relation to the different stage of the interventional procedure, was also evident, the more invasive the procedure the greater the impact on rSO(2) reading. NIRS monitoring contributed to a prompt diagnosis and management of two adverse intraoperative events and helped in early evaluation of prognosis. TCCO with NIRS is a promising monitoring tool to assess the balance between oxygen supply and demand during neuroradiologic procedures. Nevertheless, some limits should be acknowledged, such as the study of the posterior circulation and artefacts related to contrast agent injection. A careful understanding of the undergoing step of the procedure as well of the possible influence of intrinsic and extrinsic factors affecting recording is important for interpretation of data.

Hepatitis C virus infection and mixed cryoglobulinemia: a striking association. The high frequency of liver involvement in cryoglobulinemia is well established. Although both etiology and pathogenesis have remained so far undefined, recent studies suggest an association of mixed cryoglobulinemia with hepatitis C virus infection. To explore this hypothesis further, we assessed the prevalence of hepatitis C virus antibodies and RNA in a large group of patients, including: (1) 35 patients with cryoglobulinemia without clinical evidence of liver involvement (group 1), (2) 15 patients with symptomatic cryoglobulinemia associated with chronic liver disease (group 2) and (3) 12 patients with asymptomatic cryoglobulinemia associated with chronic liver disease (group 3). Anti-hepatitis C virus antibodies were detected by a second-generation enzyme-linked immunosorbent assay and third-generation immunoblot (SIA Prototype RIBA), whereas the polymerase chain reaction was used for the detection of viral RNA. Anti-hepatitis C virus antibodies, as detected by enzyme-linked immunosorbent assay, were demonstrated in 21 (60%) patients from group 1, 11 (73.3%) from group 2 and 10 (83.3%) from group 3. The immunoblot identified as positive 3 further patients in group 1 (giving a prevalence of 68.6%) and all patients in groups 2 and 3. Hepatitis C virus RNA was demonstrated in cryoprecipitates from 21 of 24 immunoblot-positives and from 6 of 11 immunoblot-negatives, indicating an actual active viral replication in 77.1% of group 1. This was also found in 13 (86.7%) and 10 (83.3%) cryoprecipitates of groups 2 and 3, respectively. Type II cryoglobulinemia was the prevalent form in group 1 (88.6%) and group 2 (73.3%), whereas type III was found in group 3 (58.3%) and in 26.7% of group 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Held-breath self-gating technique for radiotherapy of non-small-cell lung cancer: a feasibility study. To examine the feasibility of a held-breath self-gating (HBSG) technique in the radiotherapy of lung cancer. Sixteen consecutive eligible and consenting patients undergoing radiotherapy for non-small-cell lung cancer were accrued for this study. The patients underwent a standardized training session and were then asked to breath hold at four points in the breathing cycle (maximal and end tidal, inspiration and expiration) while under fluoroscopic visualization. Plain films and video imaging with digital image analysis were used to record and measure the movement of the diaphragm, a tumor surrogate, in the superior-inferior axis. These measurements were obtained during and between multiple separate breath holds within one session and between breath holds in sessions held at least one day apart. Maximal inspiration and expiration tend to provide the best positional reliability, and the standard deviation of diaphragmatic position ranged from 0.13 to 2.57 mm, with an average of 0.97 mm. During a single breath hold, the diaphragmatic movement averaged 2.62 mm with a standard deviation of 1.28 mm. The day-to-day variation of diaphragmatic positions was less than 5 mm. The held-breath self-gating technique resulted in a reduction of diaphragmatic movement by an average of 11.9 mm when compared to that seen during tidal breathing. In the radiotherapeutic management of non-small-cell lung cancer, this HBSG technique offers a simple method that provides superior immobilization of the diaphragm compared to tidal breathing. Clinical implementation of this technique should allow for a reduction of treatment margins, thus sparing more normal tissues and facilitating dose escalation.

The role of disc cell heterogeneity in determining disc biochemistry: a speculation. The nucleus pulposus is a key player in very early disc degeneration. In the young disc, by acting as a water-like fluid, as opposed to a solid, it resists compression and instantaneously distributes forces evenly in all directions to the inner annulus. The disc anlage notochordal cells contribute not only to how the disc develops, but also to the matrix of the young disc at a time when the nucleus is at its most fluid-like. In humans, the notochordal cells disappear early, when there is a transformation of the nucleus into a more solid cartilaginous tissue. In cell culture, the co-cultures of the notochordal cells and chondrocytic cells enhance proteoglycan synthesis by the opposite cell type due, at least partly, to soluble factors. The continued presence of notochordal cells in vivo may provide protection. In work by others, in vivo reinsertion of notochordal-rich nucleus pulposus in a damaged disc will delay annular degeneration. The notochordal cells in the nucleus may have a different phenotype from when they are in the notochord and they may go through a changing programme of expression critical to disc development and maintaining a fluid-like nucleus. Little is known about why, in many species, the notochordal cells die early during growth and only the chondrocytic cells persist. This area offers an interesting avenue of research that may lead to very early intervention in disc degeneration.

Longitudinal study of hormonal and physical development in young twins. Information on the correlation of normative reproductive hormone levels with physical development (Tanner stages) during puberty and on the influences of genes and environment on variation in these hormones and Tanner stages is limited. One hundred twelve healthy 9-year-old twin pairs (n = 224) took part in a longitudinal study, of which 89 pairs participated again at age 12 years (n = 178). Morning urinary LH, FSH, estradiol, and salivary testosterone levels, determined by competitive immunoassays, were measured. Tanner stages were determined through physical examination. Over the 3-year interval, all hormone levels showed a 2- to 9-fold increase. LH and FSH at age 9 years predicted sex-specific Tanner stages at age 12 years in both boys and girls. Most of the associations between hormone levels at age 9 years and physical development at 12 years were explained by genetic influences. FSH in 9-year-old boys correlated with all hormone levels and Tanner stages at age 12 years. Moderate to high heritability estimates were found for hormone levels at both ages and in both sexes. In girls a shift from environmental (age 9 years) to genetic influences (age 12 years) was found for estradiol and pubic hair development, and for breast development a shift in the opposite direction was seen. During development LH and FSH (and testosterone in boys) levels predict secondary sexual characteristics in boys and girls 3 years later. These correlations are largely due to genes that are involved in both early pubertal hormone levels and subsequent physical development.

Determination of phenolic endocrine disrupting chemicals and acidic pharmaceuticals in surface water of the Pearl Rivers in South China by gas chromatography-negative chemical ionization-mass spectrometry. An analytical method for phenolic endocrine disrupting chemicals and acidic pharmaceuticals in river water was developed using gas chromatography mass spectrometry (GC-MS) coupled with negative chemical ionization (NCI) technique, and used for the determination of these compounds in the Pearl Rivers (Liuxi, Zhujiang and Shijing Rivers). Derivatization using pentafluorobenzoyl chloride (PFBOCl) and pentafluorobenzyl bromide (PFBBr) before GC-MS analysis were applied and optimized for phenolic compounds and acidic compounds, respectively. The target compounds were analyzed for river waters from the upstream to downstream of the Pearl Rivers. Phenolic compounds 4-tert-octylphenol (4-t-OP), 4-nonylphenol (4-NP), bisphenol-A (BPA), estrone (E1), estradiol (E2) and triclosan (TCS) were detected at trace or low levels in the water samples from Liuxi River and Zhujiang River. Diethylstilbestrol (DES) was not detected in the Pearl Rivers. The highest concentrations of the phenolic compounds were found in Shijing River, and they were 3150 ng/L for 4-t-OP, 11,300 ng/L for 4-NP, 1040 ng/L for BPA, 79 ng/L for E1, 7.7 ng/L for E2 and 355 ng/L for TCS, respectively. Only a few acidic pharmaceuticals were detected at low concentrations in water from Liuxi River and Zhujiang River, but the highest concentrations for the acidic pharmaceuticals were also found in Shijing River. The highest concentrations detected for clofibric acid, ibuprofen, gemfibrozil, naproxen, mefenamic acid and diclofenac were 17 ng/L, 685 ng/L, 19.8 ng/L, 125 ng/L, 24.6 ng/l and 150 ng/L, respectively. The results suggest Liuxi and Zhujiang Rivers are only slightly contaminated and can be used as drinking water sources, but Shijing River is heavily polluted by the wastewater from nearby towns.

Aspects of MR image distortions in radiotherapy treatment planning. Registration of computed tomography (CT) and magnetic resonance (MR) images are commonly performed to define the different target regions used in radiotherapy treatment planning (RTTP). The accuracy of target definition will then depend on the spatial accuracy of the CT and MR data, and on the technique used to register the images. CT images are usually regarded as geometrically correct, while MR images are known to suffer from geometric distortion. The aim of this paper is to discuss the possible impact of MR image distortions in the radiotherapy treatment planning process. The origin, magnitude, and relative impact of the different sources of geometric distortions that affect the MR image data at different magnetic fields and for different acquisition settings are described. Techniques for distortion correction are reviewed, and their limitations are outlined. The sensitivity of image registration techniques to the presence of geometric distortions in the MR data is discussed. Finally, an overview of image registration techniques used and results obtained in clinical radiotherapy treatment planning applications is given. Spatial distortions in MR images vary with field strength and with the image acquisition protocol. The spatial accuracy generally decreases with distance from the magnet isocenter. Distortion correction techniques based on phantom evaluations cannot adequately model patient-induced distortions. Image protocols with high gradient bandwidths should be used to reduce the spatial distortions in MR images. Correction techniques based only on phantom measurements could be sufficient at low magnetic fields, while at higher fields additional corrections of patient-related distortions might be needed. Registration techniques based on matching of Landmark points located far from the magnet isocenter are especially prone to MR distortions.

Developing alternative delivery systems for methacholine challenge tests. The two American Thoracic Society recommended aerosol delivery devices for methacholine challenge testing are both obsolete and often very difficult to acquire, leading to the test being done with a number of nonstandardized nebulizers. Of the two recommended devices, one is the English Wright nebulizer used in the 2-min tidal breathing method, and the other is the DeVilbiss 646 nebulizer used in the five-breath dosimeter method. The purpose of this study was to evaluate the in vitro performance of potential alternative devices that would be economically viable and would minimize environmental contamination. One device was the disposable breath-actuated AeroEclipse(®) II BAN as a potential delivery system for the 2-min tidal breathing, and the second was the automated system by VIASYS as an alternative to either the 2-min tidal breathing or the five-breath dosimeter method. A breath simulator mimicked an adult or small child breathing pattern, and a slow inhalation for the five-breath method was generated by a spirometry calibration syringe. Methacholine (Provocholine™) was eluted from filters at the "mouth" and assayed by high-pressure liquid chromatography. In 12 sec, the AeroEclipse II BAN would be expected to have a pulmonary deposition equivalent to the 2-min tidal breathing with the English Wright, whereas the VIASYS system would take approximately 40 sec for the equivalent delivery. The per-breath delivery of the VIASYS and the DeVilbiss 646 was approximately the same, whereas one breath from the AeroEclipse II BAN was the equivalent of five from the DeVilbiss 646. These data will allow for planning in vivo studies to develop methacholine challenge protocols using modern aerosol delivery systems.

The role of ultrasound in gynecological emergencies. The expanding use of ultrasonography in gynecology puts increasing strain on the resources of ultrasound departments; any mechanism to increase the diagnostic efficiency of the scan and reduce unwarranted investigation would, therefore, be welcome. This prospective study examines the use of abdominal ultrasound examination in gynecological emergencies over a 6-month period in a London teaching hospital. The examination changed the clinical management in 33% of cases where the pregnancy test was positive, but in only 14% where it was negative. In the former group, the confirmation of viable intrauterine pregnancy reassured both patient and clinician in 84% of the cases, making the test a useful investigation in 89% of the total cases where the pregnancy test was positive. When the pregnancy test was negative, the ultrasound scan was more likely to be useful if requested by doctors with gynecological experience. In cases of incomplete spontaneous abortion, ultrasound was not found to be a useful investigation. Access to ultrasound equipment by, and basic ultrasound training of admitting junior doctors with gynecological experience would reduce referrals to the ultrasound department and reduce admissions to hospital, whilst improving appreciation of the role of ultrasound in gynecological emergencies.

Campylobacter in ready-to-eat foods: the result of a 15-month survey. Ready-to-eat foods at retail and catering establishments were randomly sampled at the point of sale for a period of 15 months. During this period, 4,469 food samples were examined for the presence of Campylobacter with the use of plate-based methodology. A range of different ready-to-eat food types, all of which have the potential to be contaminated with the organism, were examined. No viable Campylobacter cells were detected in any of the foods during the survey. There is no evidence that the foods examined in this study represent a risk to the consumer. Although these foods may be a vehicle for infection if cross-contamination occurs, other sources need to be investigated as causes of enteric infection caused by Campylobacter.

Proximal left anterior descending coronary artery stenosis should be considered when using the prognostic value of the residual SYNTAX score: Data from 10343 consecutive patients with long-term follow up in the real world. The purpose of this study was to assess the prognostic significance of the residual SYNTAX score (rSS) in a large-scale cohort of consecutive percutaneous coronary intervention (PCI) patients and to analyze whether residual proximal left anterior descending coronary artery (pLAD) lesions affect the prognosis of patients with same or similar rSS levels. The rSS, measured after PCI, has been assessed as an independent predictor of long-term clinical outcome and a tool for quantification of incomplete revascularization, and still needs to be validated in various PCI populations. When using rSS to determine an objective level of reasonable incomplete revascularization, it is currently undefined whether a pLAD lesion deserves more attention. The calculations of baseline SYNTAX scores (bSS) and rSS were performed in 10,343 consecutive patients undergoing PCI in Fuwai Hospital from January 2013 to December 2013. The primary endpoint was major adverse cardiac events (MACE), defined as a composite of all-cause death, myocardial infarction (MI), and any revascularization. Secondary endpoints included the individual components of the MACE, cardiac death, and all-cause death/MI. MACE and cardiac death rates were significantly higher among patients with residual pLAD stenosis ≥70%. rSS and residual pLAD stenosis ≥70% were both strong independent predictors of MACE. Compared with rSS, rSS plus residual pLAD stenosis was superior in predicting 30-month MACE (P = .0016). rSS is a strong independent predictor of long-term adverse clinical outcomes. Residual pLAD lesions affect the prognosis of patients with same or similar rSS levels.

Recombinant factor VIIa in the treatment of bleeding. Recombinant factor VIIa (rFVIIa) has become available for treating people with hemophilia with inhibitors who experience bleeding or require surgery. It has become apparent that rFVIIa is useful in controlling bleeding in a variety of clinical situations. This review attempts to collate and summarize the nonhemophilia applications of rFVIIa. The theoretical mechanism for the coagulation and hemostatic effects of rFVIIa are discussed. The dosage and clinical administration are described. The potential uses for patients with liver disease, anticoagulation-induced bleeding, surgery, thrombocytopenia, thrombasthenia, von Willebrand disease, and other bleeding disorders are reviewed. The use of rFVIIa is evolving, and the indications, dosage, and precautions or contraindications need to be further described and defined. It is an expensive therapy and needs to be prescribed judiciously. This review is meant to be an introduction to this new hemostatic reagent. The uses for rFVIIa will evolve as more studies are published.

Evidence for electrohydrodynamic convection as a source of spontaneous self-ordering in porous anodic alumina films. A comparative study of self-ordering behaviour of anodic alumina films fabricated in a series of diluted (down to 0.05 M) oxalic acid electrolytes allowed developing a relationship between the supporting electrolyte concentration and self-ordering voltages for the formation of porous oxide materials. Besides its practical importance, this work elucidates some fundamental principles of porous alumina formation, e.g. it suggests that the cell patterning arises from the electrohydrodynamic (EHD) convection process rather than the interfacial tension gradients near the anode surface (Marangoni-type instability).

[The interaction of hexamethonium derivatives with the cholinesterases of vertebrates and invertebrates. The physicochemical and conformational aspects]. Conformational and geometrical properties of the hexamethylenebis(trimethylammonium) (CH3)3N+-(CH2)6)-N+(CH3)3 (hexamethonium) and its derivatives with various degree of conformational flexibility of interonion chain having disulfide or two dimethylsilane groups or difluoromethylene chain instead of cholinesterase reversible inhibitors have been determined using molecular mechanics methods. Conformation-activity relationships between these inhibitors and different cholinesterases (human erythrocyte acetylcholinesterase, horse plasma butyrylcholinesterase, cholinesterase from the brain of the grass frog Rana temporaria and optical ganglia from the Pacific squid Todarodes pacificus and Comandor squids Berryteuthis magister from various areas) were investigated. Hypothesis of complex influence of conformational and geometrical properties (if molecules on anticholinesterase efficiency of compounds under investigation was formulated.

Photolysis of sulfamethoxypyridazine in various aqueous media: aerobic biodegradation and identification of photoproducts by LC-UV-MS/MS. Sulfonamides are one of the most frequently used antibiotics worldwide. Therefore, mitigation processes such as abiotic or biotic degradation are of interest. Photodegradation and biodegradation are the potentially significant removal mechanisms for pharmaceuticals in aquatic environments. The photolysis of sulfamethoxypyridazine (SMP) using a medium pressure Hg-lamp was evaluated in three different media: Millipore water pH 6.1 (MW), effluent from sewage treatment plant pH 7.6 (STP), and buffered demineralized water pH 7.4 (BDW). Identification of transformation products (TPs) was performed by LC-UV-MS/MS. The biodegradation of SMP using two tests from the OECD series was studied: Closed Bottle test (OECD 301 D), and Manometric Respirometry test (OECD 301 F). In biodegradation tests, it was found that SMP was not readily biodegradable so it may pose a risk to the environment. The results showed that SMP was removed completely within 128 min of irradiation in the three media, and the degradation rate was different for each investigated type of water. However, dissolved organic carbon (DOC) was not removed in BDW and only little DOC removal was observed in MW and STP, thus indicating the formation of TPs. Analysis by LC-UV-MS/MS revealed new TPs formed. The hydroxylation of SMP represents the main photodegradation pathway.

Multiple vitamin status in Crohn's disease. Correlation with disease activity. We measured serum, blood, or red cell concentrations of various vitamins in 24 patients with Crohn's disease who had been free from any nutritional treatment, and compared them with those in 24 healthy controls. Twelve of the patients were affected in the small bowel only, two in the large bowel only, and the remaining 10 in both the small and large bowel. The fat-soluble vitamins A and E were significantly decreased in patients with Crohn's disease compared to controls. Among the water-soluble vitamins, vitamins B1, B2 and B6 and folic acid were more depleted in patients with Crohn's disease than in the controls, whereas vitamins B12 and C, nicotinic acid, and biotin were not different between the two groups, and pantothenic acid was increased in patients with Crohn's disease. In addition, vitamin B2 and nicotinic acid showed a negative correlation with the Crohn's disease activity index. These findings suggest that there is a variety of vitamin deficiencies in Crohn's disease prior to treatment and also that concentrations of some vitamins, such as vitamin B2 and nicotinic acid, may reflect the severity of the disease.

Duodenal rupture due to blunt trauma: a problem in diagnosis. In our review of ten cases of duodenal disruption due to blunt trauma, we found a 30% mortality. Since early diagnosis would have lowered morbidity and mortality, a high index of suspicion needs to be maintained, combined with an aggressive diagnostic approach. Successful operation demands thorough duodenal exploration and facility with different methods of management.

Brain biochemistry in Williams syndrome: evidence for a role of the cerebellum in cognition? To determine what biochemical changes may occur in the brain in Williams syndrome (WS) and whether these changes may be related to the cognitive deficits. WS is a rare, congenital disorder with a characteristic physical, linguistic, and behavioral phenotype with known cognitive deficits. We obtained 31P magnetic resonance spectra (MRS) from a region consisting of mostly frontal and parietal lobe of 14 patients with WS (age, 8 to 37 years) and 48 similarly-aged controls. 1H MRS (27 cm3) localized to the left cerebellum obtained from the WS cohort were compared with those from 16 chronological age- and sex-matched normal controls. A battery of cognitive tests were administered to all subjects undergoing 1H MRS. WS brains exhibited significant biochemical abnormalities. All 31P MRS ratios containing the phosphomonoester (PME) peak were significantly altered in WS, suggesting that PME is significantly decreased. Ratios of choline-containing compounds and creatine-containing compounds to N-acetylaspartate (Cho/NA and Cre/NA) were significantly elevated in the cerebellum in WS cf. controls, whereas the ratio of Cho/Cre was not altered. This suggests a decrease in the neuronal marker N-acetylaspartate in the cerebellum. Significant correlations were found between the cerebellar ratios Cho/NA and Cre/NA and the ability of all subjects at various neuropsychological tests, including Verbal and Performance IQ, British Picture Vocabulary Scale, Ravens Progressive Matrices, and Inspection Time. The correlations can be interpreted in two ways: 1) Our sampling of cerebellar biochemistry reflects a measure of "global" cerebral biochemistry and is unrelated to cerebellar function, or 2) The relations indicate that cerebellar neuronal integrity is a requirement (on a developmental time scale or in real-time) for ability on a variety of cognitive tests.

Feed and reproductive efficiency differences between divergently selected lines for birthweight environmental variability in mice. Sustainability has come to play an important role in agricultural production. A way to combine efficiency with sustainability might be by searching for robust animals that can be selected for the homogeneity of certain traits. Furthermore, the optimization of feed efficiency is one of the challenges to improve livestock genetics programmes, but this might compromise reproductive efficiency. Animals from two divergent mouse lines, regarding variability of birthweight, were used to check whether homogeneity was also related to both feed and reproductive efficiency. The objective of this study was to use these divergent lines of mice to compare them with their feed efficiency and the reproductive capacity. Animal weight, weight gain, feed intake, relative intake and cumulated transformation index were considered as feed efficiency traits. Animals from the low line had both lower weight and feed intake from 21 to 56 days. They had a worse transforming index in the three last weeks when litter size was fitted as an effect of the model, but the lines become similar if the higher litter size of the low line was not included. Reproductively, the low line performed better considering the number of females having parturitions, the number of parturitions, and with higher litter size and survival in both parturitions. Hence, the low variability line was preferred because of reproductive efficiency without seriously affecting its feed efficiency. Homogeneity seemed to be related to robustness with similar feed efficiency but higher reproductive efficiency.

Macrophages have a grip on the gut. We host a world inside, and every day, new evidence reveals how relevant our microbiota is for daily living. In the most recent issue of Cell, Muller and colleagues demonstrate that microbiota commensals also influence colon peristalsis via a direct effect of muscolaris externae macrophages (Muller et al., 2014).

Growth of a limb spinal nerve: an ultrastructural study. A quantitative study of the delivery of nerve fibres to the developing limb has been made. Electron microscope (EM) sections of SN 9 in Xenopus were taken at close intervals between dorsal root ganglion and limb-bud. Numbers and types of axons in each section were counted. Counts declined steadily with distance from the ganglion towards the base of the limb. This is large due to some axons not having grown the full distance at the time of fixation. The slope corresponded with an outgrowth velocity of 0.5 mm a day, without branching. Distally, at stages 50 and 51, but not at stages 49 and 54, the decline was reversed, and a peak of axon number was found. This is strong evidence for axon branching in this region. Since this took place at least one stage before SN 9 bifurcated, and since the bifurcation was distal to the branching when it did appear, it is suggested that axon branching at a nerve bifurcation might be part of a trial-and-error mechanism for pathway selection. Observations were made on the sheath surrounding the nerve, and on its assembly. Initially, axons grow out naked and not parallel; Schwann cells migrate after the growing front. Processes of these cells collect individual axons, and transfer them inwards to form the primitive parallel fibre bundle, enclosed by a family of Schwann cells. Myelination later occurs in a similar manner: Schwann-cell processes extend into a bundle of naked axons and eventually encircle a single transitional axon, with one Schwann cell eventually containing many such axons. Finally comes the stage of promyelin, in which a single Schwann cell encircles a single axon. Myelin whorls are then formed from this complex.

Fruit and vegetable intake and liver cancer risk: a meta-analysis of prospective cohort studies. The associations of vegetable and fruit intake with liver cancer risk have been inconsistent based on epidemiological studies. The present study aimed to quantitatively evaluate these associations with prospective cohort studies. A systematic literature search was performed with PubMed and Scopus databases up to June 2019. Multivariate-adjusted relative risks (RRs) with a corresponding 95% confidence interval (CI) for the highest versus lowest category were pooled by using a random-effects model. Pre-specified subgroup and univariate meta-regression analyses were performed to identify the sources of heterogeneity. Dose-response analysis was conducted by using the variance weighted least squares regression model. Nine independent prospective cohort studies with 1703 liver cancer events and 1 326 176 participants were included for data synthesis. The summary estimates showed that higher vegetable intake was associated with a 39% (95%CI: 0.50, 0.75) reduction in liver cancer risk, with no significant between-study heterogeneity (P = 0.057). Dose-response analysis indicated that the risk of liver cancer was reduced by 4% (95%CI: 0.97, 0.95; P for trend <0.001) with a 100 gram per day increment of vegetable intake. Subgroup analysis showed that higher intakes of vegetables were associated with a 50% (95%CI: 0.35, 0.72) reduction of liver cancer risk in males, but not in females. However, a non-significant association was found between fruit intake and liver cancer risk. The present study provides strong evidence that higher intakes of vegetables would have beneficial effects on the prevention of liver cancer, especially for males.

Catalytic Phosphite Hydrolysis under Neutral Reaction Conditions. Cationic phosphametallocene-based platinum(II) aqua complexes were used as efficient precatalysts for the hydrolysis of aromatic and aliphatic tertiary phosphites under neutral reaction conditions at room temperature, leading to the selective cleavage of one P-O bond of the phosphite. NMR labeling experiments combined with stoichiometric model reactions and theoretical density functional theory calculations, performed with the appropriate model compounds, shed light on the operative catalytic cycle, which comprises intramolecular water molecule transfer to the cis-coordinated phosphite molecule.

Schizotypal traits and their relation to rejection sensitivity in the general population: Their mediation by quality of life, agreeableness and neuroticism. Schizotypal traits are a cluster of personality styles suggesting a potential liability for schizophrenia-spectrum disorders. Interpersonal schizotypal traits include cognitive disorganisation which consists of social anxiety, and introvertive anhedonia which consists of a lack of pleasure in social activities. Rejection sensitivity is evident all along this continuum. This study aimed to determine whether psychosocial quality of life (QOL), neuroticism and agreeableness mediates the relation between schizotypy and rejection sensitivity. Three hundred and eighteen participants from a predominantly University student population completed an online survey measuring schizotypy, rejection sensitivity, quality of life, and the five-factor personality traits. A regression analysis determined the prediction of rejection sensitivity by schizotypy, quality of life, and the five personality traits. Analyses examined the mediation of the relation between interpersonal schizotypy and rejection sensitivity by psychological QOL, social QOL, neuroticism, and agreeableness. Cognitive disorganisation and introvertive anhedonia predicted greater rejection sensitivity, which in turn were mediated by psychological QOL, social QOL, neuroticism, and agreeableness. The findings show that interpersonal schizotypy relates to greater rejection sensitivity. Psychosocial factors that lower one's ability to have positive feelings, trusting relationships, and prosocial behaviour, and personality traits that increase worrying mediate this association.

[Hydro-chemical properties of litter layer in two kinds of plantations in Beijing Xishan Mountain]. The study on the hydro-chemical properties of litter layer in Pinus tabulaeformis and Querous variabilis plantations in Beijing Xishan Mountain showed that after the precipitation passed through the plantations and penetrated into litter layer, the element concentrations in precipitation changed greatly. The concentrations of K+, Na+, Ca2+, Mg2+, NH4+ -N and NO3- -N in litter water had similar changing trends as those in throughfall. The average concentrations of K+, Na+, Ca2+ and Mg2+ in litter water were higher than those in throughfall, but NH4+ -N and NO3- -N were in adverse. Ca2+ increased most, with the increment of 7.54 mg x L(-1) in Q. variabilis plantation and 5.27 mg x L(-1) in P. tabulaeformis plantation. The concentrations of K+, Na+, Ca+, Mg2+ in litter water were higher in Q. variabilis than in P. tabulaeformis plantation, but NH4+ -N and NO3- -N concentrations were lower in Q. variabilis than in P. tabulaeformis. After leaching by precipitation, the nutrients return into woodland was 41.59 kg x hm(-2) in Q. variabilis and 58.12 kg x hm(-2) in P. tabulaeformis, among which, Ca2+ returned more, followed by K+.

High frequency of the TARDBP p.Ala382Thr mutation in Sardinian patients with amyotrophic lateral sclerosis. Recently, rare mutations in the TARDBP gene have been identified in familial and sporadic amyotrophic lateral sclerosis (ALS) patients. The purpose of this study was to characterize the genetic variability of the TARDBP gene in a cohort of Sardinian ALS patients. The coding region of the gene was analyzed in 97 unrelated patients previously tested negative for superoxide dismutase (SOD1) mutations. The p.Ala382Thr (c.1144G>A) mutation was found in 30 patients (30.9%). The mutation was predominant in familial ALS patients (FALS) as it was represented in 24 of 30 FALS cases (80%) (p < 0.0003). Six cases were apparently sporadic (9% of sporadic ALS patients). No further mutation of TARDBP was found in our cohort of ALS patients. Patients carrying the mutation showed spinal site of onset in 24 cases (80%), an average age at onset of 54.7 ± 11.1 years, not significantly different from patients not harboring TARDBP mutations (56.7 ± 9.6) and a female:male gender ratio of 1:1.1. The haplotype analysis carried out using eight microsatellite markers flanking the gene showed a founder effect for this mutation. Finally, we estimated the age-specific penetrance of the TARDBP p.Ala382Thr mutation in an additional sample of 47 carriers (20 affected and 27 unaffected). The average penetrance to 70 years was 60% (95% confidence interval 41-79%). A trend toward a higher penetrance in males was observed. Even in the presence of a causal mutation, most of the ALS clinical heterogeneity, however, draws upon from a multifactorial context.

Rate of LCAT-mediated cholesterol esterification and serum lipids during etiroxate therapy in hyperlipoproteinemia. Changes in the rate of the plasma cholesterol ester production mediated by lecithin: cholesterol acyltransferase (LCAT, E.C. 2.3.1.43) were examined in 15 patients suffering from types II and IV HLP who had been treated for 14 weeks with etiroxate. Whereas the plasma cholesterol concentration decreased significantly only in the initial phase of the therapy, the rate of cholesterol esterification increased gradually and attained at the end of the study a value exceeding by 50% the initial level. The final fractional turnover rate nearly equalled that characteristic for the control group of healthy subjects, in spite of the fact that the concentration of plasma cholesterol in the diseased subjects was higher by 50-100%. Triglyceride concentration decreased only transitorily in the course of the therapy with etiroxate. It is concluded that etiroxate is likely to normalize the rate of cholesterol turnover in the endogenous pool.

Usefulness of a job-exposure matrix 'MADE' as a decision tool for compensation of work-related musculoskeletal disorders. We aimed to assess the predictivity of the biomechanical job-exposure matrix 'MADE' using compensation data from the National Health Insurance for work-related disorders. Data were obtained from 2013 to 2015, area under curves (AUC), sensitivity, specificity and predictive values were calculated using compensation results as reference. We collected 163 128 cases data. AUC ranged from 0.64 for shoulders disorder to 0.82 for knee disorders. If two thresholds were considered, 28.7% of the sample fit under or over those. The matrix showed a fair predictivity. Such matrix cannot replace expertise but might be a tool used for improving compensation process.

Feline immunodeficiency virus is concentrated in milk early in lactation. We studied mother-to-offspring transmission of feline immunodeficiency virus (FIV), focusing on milk-borne virus transmission in order to assess its similarities to perinatal HIV transmission. We also attempted to evaluate the influence of intragestational treatment with 9-[2-(phosphono-methoxy)-propyl]adenine (PMPA) on virus transmission to offspring. Eleven female cats (queens), chronically infected with FIV-B-2542 and bred to an FIV-negative male, produced a total of 25 viable and 18 nonviable term kittens. Overall, the vertical transmission rate by untreated queens was 22%, similar to that for HIV, which unfortunately precluded adequate assessment of PMPA efficacy. However, at delivery 9 of 10 queens (90%) had higher viral RNA loads in milk (4 x 10(4) to 4 x 10(8) viral copies/ml) than in plasma (5 x 10(3) to 2.5 x 10(6) viral copies/ml). Conversely, 10 of 11 queens (91%) had lower proviral loads in milk cells (0 to 10(2) proviral copies/microg DNA) than blood cells (10(2) to 10(4) proviral copies/microg DNA). Thus, FIV is concentrated in early milk despite relatively low proviral loads in milk cells, suggesting that virus may be actively secreted by the mammary gland for dissemination to offspring. FIV provides a model for the study of milk-borne lentivirus transmission and assessment of strategies to reduce postnatal HIV vertical transmission.

Implications of fear of negative evaluation, state anxiety, and implied level of target-dominance on perceptions of personality traits. Fear of negative evaluation (FNE), state anxiety (SA), and dominance have consequences for social functioning. The present study assessed how FNE, SA, and a target's dominance-relevant label are related to perceptions of personality. One hundred seventy-eight participants who scored high or low on FNE underwent a laboratory manipulation of SA, viewed a photograph of a target with a high or low dominance-relevant label, and rated the target on the Big Five personality traits and dominance. FNE and SA were unrelated to perceptions, but the high-dominance label was associated with perceptions of higher dominance, conscientiousness, and openness. In conclusion, judges did use information about others when making initial judgments of personality, but these judgments were not impacted by trait or state psychological distress.

Risk management in high-tech home care services. Advances in technology and medical knowledge, combined with economic pressures, have allowed patients formerly cared for in a hospital setting to have access to comparable services at home. These advances, however, are accompanied by new risks and liabilities for the health care provider.

Peripheral MR angiography. Atherosclerotic disease of the lower extremities is a common disorder in western society. Its debilitating nature calls for accurate diagnosis and treatment. The gold standard for diagnosing this disease by depiction of vessel morphology is X-ray angiography (either conventional or digital subtraction angiography). However, the invasive nature of this technique and the possible harmful effects of iodinated contrast agents have led to the idea that non-invasive MR angiography might be a good alternative for acquiring information about vessel morphology. Most extensively studied was time-of-flight MR angiography. Although first results with this technique were encouraging, it is now apparent that time-of-flight MR angiography is hampered by the virtue of which it exists, since blood flow not only generates vessel-to-background contrast, but is also the cause of disturbing artifacts. However, with the introduction of minimally invasive contrast-enhanced MR angiography, using gadolinium chelates to reduce the T1 of blood, image quality has improved dramatically. Moreover, using contrast-enhanced MR angiography, high-resolution three-dimensional data about the entire peripheral vascular tree can be obtained within several minutes, which might make MR angiography a true competitor of X-ray angiography as a diagnostic tool in the clinical work-up of a patient with complaints of peripheral atherosclerosis. The purpose of this article is to explain working mechanisms and usefulness of both time-of-flight and contrast-enhanced MR angiography.

Linking micromorphism, brooding, and hermaphroditism in brachiopods: insights from Caribbean Argyrotheca (Brachiopoda). In extant brachiopods, parental brooding of the larvae occurs exclusively within Rhynchonelliformea. Methods of larval protection range from simple retention of the larvae within the mantle cavity, to sophisticated brood care within highly specialized brood pouches found in Argyrotheca and Joania (Terebratulida, Megathyridoidea), Gwynia (Terebratulida, Gwynioidea), and all Thecideoidea (Thecideida). Previous studies on the reproductive biology of Argyrotheca yielded contrasting results on the epithelial origin of the brood pouches in this genus. Here, representatives of different species of Argyrotheca from the Belize Barrier Reef were examined using histological section series. Brood pouches of four species, A. cf. schrammi and Argyrotheca sp. 1-3, are of the same basic structure, formed by invaginations of the anterior body wall and connected to the visceral cavity via the metanephridia. The same four species are simultaneously hermaphroditic, suggesting that fertilization is achieved, at least partly, through selfing. One species, Argyrotheca rubrocostata, differs significantly from all others as it has no brood pouch and gonochoric gonads. Thus, the presence of brood pouches and simultaneous hermaphroditism are concluded to be correlated within Megathyridoidea and proposed to be homologous traits of Joania and several but not all species of Argyrotheca, questioning the monophyletic status of both genera. In contrast to the brood pouches of Thecideoidea, lophophoral epithelium is not involved in the formation of the pouches of Argyrotheca and Joania. Therefore, megathyridoid and thecideoid brood pouches are not homologous but evolved independently within rhynchonelliform brachiopods. All brachiopods with brood pouches share a micromorphic form and a short life span, limiting the space and time available for gamete and larval development. We suggest that the brood pouches and the hermaphroditic gonads of Argyrotheca spp. and Joania compensate these limitations by minimizing the loss of gametes and larvae, and by maximizing the chances of successful fertilization.

Regional variation of cell proliferation within the facial processes of the chick embryo: a study of the role of 'merging' during development. Variation in rates of cell proliferation along the long axis of the maxillary process, within the lateral nasal process and in the zone of attachment between these structures was analyzed employing DNA labeling indices. Chick embryos were labeled with [3H]thymidine for 1 h and processed for histology and autoradiography. The percentage of labeled mesenchymal cells was determined in delineated areas. Analysis of labeling indices indicated that rates of cell proliferation varied within each of the facial processes. Regions where rates of proliferation were maintained at elevated levels were the boundary areas of the facial processes (e.g. the anterior tip of the maxillary process) and the zones of attachment between the facial processes (e.g. between the maxillary process and the lateral nasal process). Despite the presence of elevated rates of proliferation in selected regions within the facial processes, however, the percentage of labeled cells in all areas declined with advancing developmental age. These findings support the hypothesis, proposed by Streeter and Patten, that the 'merging' of adjacent facial primordia, such as the maxillary and lateral nasal processes, is accomplished by elevated rates of cell proliferation within the zones of attachment compared to the rates of proliferation in adjacent regions.

Intracellular formation of α-synuclein oligomers and the effect of heat shock protein 70 characterized by confocal single particle spectroscopy. Synucleinopathies such as dementia with Lewy bodies or Parkinson's disease are characterized by intracellular deposition of pathologically aggregated α-synuclein. The details of the molecular pathogenesis of PD and especially the conditions that lead to intracellular aggregation of α-synuclein and the role of these aggregates in cell death remain unknown. In cell free in vitro systems considerable knowledge about the aggregation processes has been gathered. In comparison, the knowledge about these aggregation processes in cells is far behind. In cells α-synuclein aggregates can be toxic. However, the crucial particle species responsible for decisive steps in pathogenesis such as seeding a continuing aggregation process and triggering cell death remain to be identified. In order to understand the complex nature of intracellular α-synuclein aggregate formation, we analyzed fluorescent particles formed by venus and α-synuclein-venus fusion proteins and α-synuclein-hemi-venus fusion proteins derived from gently lyzed cells. With these techniques we were able to identify and characterize α-synuclein oligomers formed in cells. Especially the use of α-synuclein-hemi-venus fusion proteins enabled us to identify very small α-synuclein oligomers with high sensitivity. Furthermore, we were able to study the molecular effect of heat shock protein 70, which is known to inhibit α-synuclein aggregation in cells. Heat shock protein 70 does not only influence the size of α-synuclein oligomers, but also their quantity. In summary, this approach based on fluorescence single particle spectroscopy, that is suited for high throughput measurements, can be used to detect and characterize intracellularly formed α-synuclein aggregates and characterize the effect of molecules that interfere with α-synuclein aggregate formation.

Effect of coronary collaterals on microvascular obstruction as assessed by magnetic resonance imaging in patients with acute ST-elevation myocardial infarction treated by primary coronary intervention. The aim of this study was to determine whether angiographically visible collaterals before reperfusion are associated with beneficial effects on infarct size, microvascular obstruction, and left ventricular function as measured by magnetic resonance imaging (MRI) in patients with ST-elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). We examined 235 patients with STEMI and symptoms <12 hours. All patients had Thrombolysis In Myocardial Infarction grade < or =1 flow before PCI. Collateral flow was graded according to Rentrop classification. Patients were divided in 2 groups; group A had absent or weak collateral flow and group B had significant flow. In 166 patients there was absent or weak collateral flow, whereas 69 had significant flow. Extent of microvascular obstruction was significantly smaller in group B at early MRI (3.3% vs 2.1% of left ventricle, p = 0.009). Infarct size measured by peak creatine kinase release showed smaller infarcts in group B (p = 0.02), whereas MRI infarct size showed a weak trend (p = 0.20). At 6 months, a strong trend toward a lower rate of death or nonfatal reinfarction could be seen in group B (4.5% vs 12.2%, p = 0.07). In conclusion, well-developed collaterals before reperfusion by PCI in patients with STEMI are associated with a protective effect on coronary microcirculation.

Multicentric Anogenital Bowen's Disease Treated with Imiquimod and CO2 Laser. A 53-year-old white woman presented to our clinic with skin lesions in the anogenital region that had persisted for 1 year. She had a past medical history of total vulvectomy for a vulvar localization of Bowen's disease. She was otherwise in good health, with no evidence of illness or immunosuppression. Physical examination revealed multiple erythematous papular lesions located in the anogenital region (Figure 1). Dermatoscopy of the anogenital papules revealed glomerular vessels on an erythematous background typical of Bowen's disease (Figure 2A). There were no palpable inguinal lymph nodes. Rectosigmoidoscopy was normal. The biopsy specimen showed full thickness keratinocyte atypia with loss of normal stratification and was conclusive for Bowen's disease (Figure 2B).

Brugada-like electrocardiogram pattern: how to stratify the risk for sudden cardiac death. Is sports activity contraindicated? Brugada syndrome is associated with a considerable risk of sudden death in young and otherwise healthy adults. The syndrome is estimated to be responsible for at least 4% of all sudden deaths and at least 20% of sudden deaths in patients with structurally normal hearts. The diagnosis of Brugada syndrome is based on peculiar electrocardiogram (ECG) abnormalities classified by the European Society of Cardiology in three types: type 1 (coved-type) is the diagnostic pattern; type 2 (saddle-back type); and type 3 are considered significant if there is a conversion to a type 1, spontaneously or during administration of class I A/C anti-arrhythmic drugs (flecainide, etc.). There is a general agreement about the high risk of sudden death in patients with previous cardiac arrest, for whom an implantable defibrillator (ICD) is recommended. In contrast, controversy exists on the correct clinical behaviour in individuals without a history of previous cardiac arrest. To stratify the risk in patients with type 1 pattern, three major factors have been suggested: typical ECG pattern in the basal state; a history of syncope; and inducible ventricular tachycardia/ventricular fibrillation during electrophysiological study (EPS). However, the indication and usefulness of an EPS is debatable. In patients with a type 2 or 3 pattern a pharmacological test is indicated in the presence of symptoms or of a familial history. With regard to sports eligibility, patients with a history of cardiac arrest should have an ICD and they can practise (low intensity) sport only after the implant of the device. Patients without documented cardiac arrest but at high risk (basal type 1 ECG pattern, syncope and/or positive EPS) should also have an ICD and they can practise (low intensity) sport only after the implant of the device. In patients at low risk (type 1 ECG pattern in the absence of symptoms, without family history and negative EPS) the behaviour regarding sport eligibility is not a matter of debate. In cases with type 2 or 3 pattern, in the absence of familial history and symptoms, a permissive behaviour should be assumed.

Embolization of immediate release transcatheter patch for atrial septal defect occlusion: the causes and the pitfalls to avoid. We report embolization of a bioabsorbable immediate-release patch for closure of atrial septal defect into left atrium with forward movement into and out of the mitral valve during each cardiac cycle. The dislodged device was ultimately explanted by a surgical operation and the defect was closed. We discuss causes and recommend tips to prevent such a serious potential complication. We also suggest some modifications to the device for making it more safe and effective.

Interaction of cesium ions with calix[4]arene-bis(t-octylbenzo-18-crown-6): NMR and theoretical study. Using (1)H, (13)C, and (133)Cs NMR spectra, it is shown that calix[4]arene-bis(t-octylbenzo-18-crown-6) (L) forms complexes with one (L·Cs(+)) and two (L·2Cs(+)) Cs(+) ions offered by cesium bis(1,2-dicarbollide) cobaltate (CsDCC) in nitrobenzene-d(5). The ions interact with all six oxygen atoms in the crown-ether ring and the π electrons of the calixarene aromatic moieties. According to extraction technique, the stability constant of the first complex is log β(nb)(L·Cs(+)) = 8.8 ± 0.1. According to (133)Cs NMR spectra, the value of the equilibrium constant of the second complex is log K(nb)((2))(L·2Cs(+)) = 6.3 ± 0.2, i.e., its stabilization constant is log β(nb)(L·2Cs(+)) = 15.1 ± 0.3. Self-diffusion measurements by (1)H pulsed-field gradient (PFG) NMR combined with density functional theory (DFT) calculations suggest that one DCC(–) ion is tightly associated with L·Cs(+), decreasing its positive charge and consequently stabilizing the second complex, L·2Cs(+). Using a saturation-transfer (133)Cs NMR technique, the correlation times τ(ex) of chemical exchange between L·Cs(+) and L·2Cs(+) as well as between L·2Cs(+) and free Cs(+) ions were determined as 33.6 and 29.2 ms, respectively.

A modified culture medium increases blastocyst formation and the efficiency of human embryonic stem cell derivation from poor-quality embryos. Human embryonic stem cells (HESCs) are defined as self-renewing cells that retain their ability to differentiate into all cell types of the body. They have enormous potential in medical applications and as a model for early human development. There is a need for derivation of new HESC lines to meet emerging requirements for their use in cell replacement therapies, disease modeling, and basic research. Here, we describe a modified culture medium containing human recombinant leukemia inhibitory factor and human basic fibroblast growth factor that significantly increases the number of human blastocysts formed and their quality, as well as the efficiency of HESC derivation from poor-quality embryos. Culturing poor-quality embryos in modified medium resulted in a two-fold increase in the blastocyst formation rate and a seven-fold increase over the derivation efficiency in conventional medium. We derived 15 HESC lines from poor-quality embryos cultured in modified culture medium and two HESC lines from quality embryos cultured in conventional culture medium. All cell lines shared typical human pluripotent stem cell features including similar morphology, normal karyotypes, expression of alkaline phosphatase, pluripotency genes, such as Oct4, and cell surface markers (SSEA-4, TRA-1-60, TRA-1-81), the ability to form teratomas in SCID mice, and the ability to differentiate into cells of three embryonic germ layers in vitro. Our data suggest that poor-quality embryos that have reached the blastocyst stage in our modified culture medium are a robust source for normal HESC line derivation.

Phyotoxicity of diesel soil contamination on the germination of Lactuca sativa and Ipomoea batatas. Phytotoxic effect of diesel contaminated soil on germination rate of Lactuca sativa and Ipomoea batatas, at two concentrations ranges (0-6ml and 0-30ml), were investigated and compared. Diesel soil contamination was simulated and soil samples were taken from contaminated soil at 1, 5,10, 15, 25, 50, 75 and 100 days should be after planting. The result showed that in both plant species, diesel inhibited germination in a concentration dependent manner, Also, the influence of diesel contamination diminished with increased time duration; suggesting possible reduction in diesel toxicity over time. However, germination of lettuce was significant and negatively correlated (r2 = -0.941) with diesel contamination as compared to sweet potato (r2 = -0.638).Critical concentration of diesel in relation to seed germination of L. sativa was lower than vegetative germination of I. batatas, indicating that germination of I. batatas was less sensitive to diesel contamination as compared to L. sativa.

Classification of B-cells according to their differentiation status, their micro-anatomical localisation and their developmental lineage. B-lymphocytes or B-cells form a diverse and flexible repertoire of immune cells that are reactive to almost all potential pathogens by means of the production of antigen-specific immunoglobulins. They can be divided into different populations or subsets, characterised by a distinct combination of properties. These subsets are identified on the base of their differentiation status (precursor B-cells, peripheral B-cells), their localisation in the micro-anatomical compartments of the B-cell follicle (marginal zone B-cells, lymphocytic corona B-cells, follicle centre B-cells), and the developmental lineage to which they belong (B-1 cells, and B-2 or conventional B-cells). The latter classification of B-cells into B-1 cells and B-2 cells is commonly followed by immunologists, mainly in the study of mice models, while pathologists and haematologists tend to use a terminology for B-cells which refers to their localisation in the micro-anatomical compartments of the B-cell follicle and/or differentiation status. In this review, we will discuss the various subsets of B-cells and point to the similarities between the various classification systems in use.

Identification of reliable spike templates in multi-unit extracellular recordings using fuzzy clustering. A method for extracting single-unit spike trains from extracellular recordings containing the activity of several simultaneously active cells is presented. The technique is particularly effective when spikes overlap temporally. It is capable of identifying the exact number of neurons contributing to a recording and of creating reliable spike templates. The procedure is based on fuzzy clustering and its performance is controlled by minimizing a cluster-validity index which optimizes the compactness and separation of the identified clusters. Application examples with synthetic spike trains generated from real spikes and segments of background noise show the advantage of the fuzzy method over conventional template-creation approaches in a wide range of signal-to-noise ratios.

Unicompartmental knee prostheses: in vitro wear assessment of the menisci tibial insert after two different fixation methods. Knee osteoarthritis is a complex clinical scenario where many biological and mechanical factors influence the severity of articular degenerative changes. Minimally invasive knee prosthetic surgery, with only a compartment replacement (unicompartmental knee replacement), might be a good compromise between osteotomy and total knee prosthesis. The focus of this study was to develop and validate a protocol to assess the fixation method of the femoral components in mechanical simulation, for pre-clinical validation; the wear behaviour of two different fixation frames was quantified and compared. In particular, two different wear tests were conducted using the same knee simulator, the same load profiles and the same kinematics; two different fixation methods were applied to the femoral sleds (synthetic femur and metal block). Surface characterization on both articulating bearings was performed by a roughness measuring machine and coordinate measuring machine. The wear produced by the tibial inserts using the synthetic femur was considerably higher than the wear registered by the metal-block holder. Roughness measurements on femoral sleds showed a limited number of scratches with high R(t) values for the metal-block set-up; the damaged surface broadened in the case of femoral condyles and tibial inserts mounted on composite bone, but lower R(t) and linear penetration values were measured. The two holding frames showed different wear activities as a consequence of dissimilar dynamic performance. Further observations should be made in vivo to prove the actual importance of synthetic bone simulations and specific material behaviour.

How do statistical properties influence findings of tracking (maintenance) in epidemiologic studies? An example of research in tracking of obesity. There is great interest in studying the tracking (maintenance) of health conditions and risk factors over the life span. Tracking is often defined as the maintenance of a distribution position (e.g., quintile or percentile) in a study population over time. This study investigated how statistical properties might influence research findings of tracking with a special attention on the tracking of extreme ranking. Our results show that when repeated measures over time were positively correlated, the probability of tracking in extreme rankings was greater than other rankings and this was closely influenced by the overall correlation (r) and by the categorization. For example, when r = 0.4, 38% remained in the bottom and upper quintile (Q1, Q5) respectively, while only 22% remained in the middle quintile (Q3); when r = 0.8, the figure became 65% vs. 32%. When r = 0.4 and 0.8, 19 and 50% remained in the upper 95th percentile (or under the 5th percentile), respectively. Our real data show that children in the upper body mass index (= weight(kg)/height(m)(2)) quintile were more likely to maintain their ranking (54%) than others (about 30%), but not significantly higher than the expected (47%, p > 0.05). In conclusion, the overall correlation should be considered when studying tracking. Our proposed methods and predicted probabilities of tracking can help test whether one's observed tracking patterns are different from the statistically predicted ones.

Comparison of molecular assays for HPV testing in oropharyngeal squamous cell carcinomas: a population-based study in Northern Ireland. Background Determination of HPV status has become clinically relevant for patient stratification under UICC TNM8 staging. Within the UK, a combination of p16 IHC and HPV DNA-ISH is recommended for classifying HPV status. This study will assess a series of clinically applicable second-line molecular tests to run in combination with p16 IHC to optimally determine HPV status. Methods The ability of HPV RNA-ISH, HPV DNA-ISH and HPV DNA-PCR to identify p16-positive/HPV-positive patients was investigated in a population-based OPSCC cohort of patients diagnosed in Northern Ireland from 2000-2011. Results Only 41% of the Northern Irish OPSCC patient population was associated with HPV-driven carcinogenesis. Both ISH assays were more specific than the DNA-PCR assay (100% and 95% vs 67%) and were less likely to be affected by pre-analytical factors such as increasing block age. A pooled HPV genotype probe for RNA-ISH was found to be the most accurate molecular assay assessed (95% accuracy) when compared to p16 positivity. Conclusions Our study demonstrates the advantage of tissue-based molecular assays when determining HPV status in retrospective samples. Specifically, we demonstrate the enhanced sensitivity and specificity of ISH techniques compared to PCR based methodology when working with FFPE tissue and found HPV RNA-ISH to be the most effective assay for determining HPV status. Impact As p16 IHC is a relatively inexpensive, accessible and sensitive test for stratifying patients by HPV status, this study finds more patients would benefit from first-line p16 IHC followed by specific HPV testing using HPV RNA-ISH to confirm HPV status.

The role of water in cell architecture. The role of water in biochemical and cellular events is ignored by most workers. However, much recent research has pointed to the importance of physical processes of the cell, which focus attention on such straight forward, elementary questions as position and relationship in space of cell components. In this communication these questions are examined in terms of a new model of water structure. A radically new feature of this model is that water clusters have long-term rather than flickering existence and are as large as the macromolecular components of the cell. These properties allow the clusters and other components to pack together spacially so giving rise to integrated, large-scale, subcellular structures. The intimate participation of water in these structures would explain the fragility of the cytoplasmic organization.

Androgen initiates Sertoli cell tight junction formation in the hypogonadal (hpg) mouse. Sertoli cell tight junctions (TJs) form at puberty as a major component of the blood-testis barrier (BTB), which is essential for spermatogenesis. This study characterized the hormonal induction of functional Sertoli cell TJ formation in vivo using the gonadotropin-deficient hypogonadal (hpg) mouse that displays prepubertal spermatogenic arrest. Androgen actions were determined in hpg mice treated for 2 or 10 days with dihydrotestosterone (DHT). Follicle-stimulating hormone (FSH) actions were studied in hpg mice expressing transgenic human FSH (hpg+tgFSH) with or without DHT treatment. TJ formation was examined by mRNA expression and immunolocalization of TJ proteins claudin-3 and claudin-11, and barrier functionality was examined by biotin tracer permeability. Immunolocalization of claudin-3 and claudin-11 was extensive at wild-type (wt) Sertoli cell TJs, which functionally excluded permeability tracer. In contrast, seminiferous tubules of hpg testes lacked claudin-3, but claudin-11 protein was present in adluminal regions of Sertoli cells. Biotin tracer permeated throughout these tubules, demonstrating dysfunctional TJs. In hpg+tgFSH testes, claudin-3 was generally absent, but claudin-11 had redistributed basally toward the TJs, where function was variable. In hpg testes, DHT treatment stimulated the redistribution of claudin-11 protein toward the basal region of Sertoli cells by Day 2, increased Cldn3 and Cldn11 mRNA expression, then induced the formation of functional TJs containing both proteins by Day 10. In hpg+tgFSH testes, TJ protein redistribution was accelerated and functional TJs formed by Day 2 of DHT treatment. We conclude that androgen stimulates initial Sertoli cell TJ formation and function in mice, whereas FSH activity is insufficient alone, but augments androgen-induced TJ function.

Hypoxanthine in deoxyribonucleic acid: generation by heat-induced hydrolysis of adenine residues and release in free form by a deoxyribonucleic acid glycosylase from calf thymus. A slow conversion of adenine residues to hypoxanthine occurs in single-stranded DNA when heated in neutral aqueous buffers. The rate of this reaction at pH 7.6 and 110 degrees C is k = 4 x 10(-8) s-1, as determined by base analysis of heat-treated DNA that contains radioactively labeled adenine residues. It is proposed that adenine deamination is one of several forms of hydrolytic damage that may occur as spontaneous premutagenic lesions in DNA in vivo. Cell extracts from calf thymus and human fibroblasts contain a DNA glycosylase activity with specifically catalyzes the release of free hypoxanthine from DNA or polydeoxyribonucleotides that contain dIMP residues. Several properties of the purified enzyme from calf thymus are described: It has an approximate molecular weight of 31 000. No cofactors are required for activity. The enzymatic release of hypoxanthine occurs readily from double-stranded polydeoxyribonucleotides that have either thymine or cytosine residues in the complementary strand. Single-stranded polymers are 10-20-fold more slowly attacked, and there is no detectable cleavage of monomeric dIMP. Hypoxanthine is liberated from DNA directly as a free base. Thus, when poly(dI) x poly(dC) containing both [3H]-dIMP and [32P]dIMP residues was employed as the substrate, 3H-labeled hypoxanthine but no 32P-labeled material was released in ethanol-soluble form. The hypoxanthine-DNA glycosylase presumably acts in DNA repair by preventing deaminated adenine residues from being expressed as mu.

[Analysis of malaria epidemic situation in Changzhou City from 2010 to 2014]. To grasp the malaria epidemic situation in Changzhou City from 2010 to 2014, so as to provide the evidence for formulating and adjusting malaria control strategies and measures. The epidemiological data of malaria cases in the special report system from 2010 to 2014 were collected, and the malaria epidemic situation and the diagnosis and treatment of malaria patients were analyzed. There were 132 malaria cases reported in Changzhou City from 2010 to 2014, with a decrease of 27.47% compared to 182 cases from 2005 to 2009. Among the 132 cases, 2 cases were local infected cases and the remaining 130 cases were imported cases. Four cases were clinically diagnosed and 128 cases were laboratory confirmed, with 97 cases of malignant malaria, 14 cases of vivax malaria, 13 cases of ovale malaria, and 4 cases of quartan malaria. The 132 cases were distributed in five districts：56 cases in Jintan City, 51 cases in Liyang City, 19 cases in Tianning District, 3 cases in Wujin District, and 3 cases in Xinbei District. The median duration between the onset and treatment of the disease was 2 days, and the median duration between the diagnosis and treatment was 1 day. The diagnosing units were concentrated on the county-level disease control agencies, and medical institutions at county and municipal levels, accounting for 92.42% (122/132). From 2011 to 2014, there were no local malaria cases. From 2012 to 2014, there have been no local malaria cases in Changzhou City, and the goal of eliminating malaria has been achieved basically. However, there are still many imported malaria cases, and the infected species are diverse. Therefore, imported malaria is still the key of malaria prevention and control.

Relationship between insulin resistance and the renin-angiotensin system: analysis for patients with essential and renovascular hypertension. Insulin resistance is frequently observed in patients with essential hypertension (EHT), and the renin-angiotensin system (RAS) has been demonstrated to modulate the status of insulin resistance. The aims of present study are to investigate the relationship between systemic RAS and insulin resistance in 82 patients with EHT and compare the impact of RAS to insulin resistance with 10 renovascular hypertension (RVHT) patients who have a highly activated systemic RAS. From patients who were admitted to our hospital, patients with overt diabetes and hypertensives who had secondary HT except RVHT or chronic renal failure were excluded. Plasma renin activity (PRA) was used as an indicator of systemic RAS activity. HOMA-R as an index of insulin resistance and sum of immunoreactive insulin (IRI) during glucose tolerance test (sigmaIRI) and IRI at 120 minutes (IRI120) were used as indices of hyperinsulinemia. In the EHT patients, circulating PRA showed an independent relationship with IRI120 and sigmaIRI after adjusting confounding factors (IRI120: t = 2.70, p = 0.01, sigmaIRI: t = 3.05, p < 0.001). Excluding patients who were taking angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II type 1 receptor blocker (ARBs), the relationship remained in univariate linear regression; after adjustment for confounding factors, PRA showed a tendency to be correlated with sigmaIRI. However, there was no significant relationship between PRA and indices of insulin resistance and hyperinsulinemia in patients with RVHT. In conclusion, the systemic RAS may modulate insulin sensitivity in EHT patients.

Induction of prolactin release by H1- or H2-histamine agonists in maturing male and female rats. Previous evidence has shown that histamine (HA) increases prolactin (PRL) release in adult male and female rats. This response is depending on the age of the animals and some differences were appreciated between male and female rats. In addition, at 20 days of age the PRL response was greater than earlier ages. The purpose of the present communication was to study further this response and to define the type of HA receptor that may be involved in the mediation of this PRL response. Animals of both sexes, at 5 or 20 days of age, were injected into the lateral brain ventricles with three log-doses of histamine (HA), 2,2, pyridilethylamine (2 PEA, and H1-histamine agonist), 4 methyl-histamine (4 MHA, an H2-histamine agonist) or saline as control. Fifteen minutes later a sample of blood was taken from the jugular vein and plasma PRL levels were determined by RIA. In complete agreement with previous work, results obtained indicate that HA is able to induce an increased PRL release in 20-day-old animals. This response was not identical in rats of both sexes. Female rats appeared to be more sensitive to HA than male rats. 2 PEA, was not able to reproduce the response in male rats but it was effective in female animals. 4 MHA induced the response in both sexes in a similar way than HA. At 5 days of age in male rats HA had no effect on PRL release. In female rats, instead, only the greater dose was able to induce a small but statistically significant response. In general, nor 2 PEA or 4 MHA were able to stimulate the PRL release at this age. The present results suggest that H2-histamine receptors are present in male rats and in female animals both types of receptors may be involved in the control of PRL release.

Healthy Eating and Leisure-Time Activity: Cross-Sectional Analysis of that Role of Work Environments in the U.S. The aim of this study was to evaluate relationships between work context and two health behaviors, healthy eating and leisure-time physical activity (LTPA), in U.S. adults. Using data from the 2010 National Health Interview Survey (NHIS) and Occupational Information Network (N = 14,863), we estimated a regression model to predict the marginal and joint probabilities of healthy eating and adhering to recommended exercise guidelines. Decision-making freedom was positively related to healthy eating and both behaviors jointly. Higher physical load was associated with a lower marginal probability of LTPA, healthy eating, and both behaviors jointly. Smoke and vapor exposures were negatively related to healthy eating and both behaviors. Chemical exposure was positively related to LTPA and both behaviors. Characteristics associated with marginal probabilities were not always predictive of joint outcomes. On the basis of nationwide occupation-specific evidence, workplace characteristics are important for healthy eating and LTPA.

A quantitative view of charge transfer in the hydrogen bond: the water dimer case. The hydrogen bond represents a fundamental intermolecular interaction that binds molecules in vapor and liquid water. A crucial and debated aspect of its electronic structure and chemistry is the charge transfer (CT) accompanying it. Much effort has been devoted, in particular, to the study of the smallest prototype system, the water dimer, but even here results and interpretations differ widely. In this paper, we reassess CT in the water dimer by using charge-displacement analysis. Besides a reliable estimate of the amount of CT (14.6 me) that characterizes the system, our study provides an unambiguous context, and very useful bounds, within which CT effects may be evaluated, crucially including the associated energy stabilization.

Utilization of homologous proteins to evaluate the safety of recombinant human proteins--case study: recombinant human interferon-gamma (rhIFN-gamma). Interferon-gamma is an immunomodulatory cytokine that has an extremely restricted host range of activities. RhIFN-gamma was one of the first species-specific recombinant proteins to be assessed in conventional safety models typically utilized for xenobiotics. Acute, subchronic and Segment I and II reproductive studies in rats revealed no evidence of toxicity at any of the doses tested; these results were not predictive of clinical toxicity, which is not unexpected since rodents are known to be pharmacologically nonresponsive to rhIFN-gamma. In contrast, 4- and 13-week multidose toxicity studies in cynomolgus monkeys with rhIFN- were predictive of many of the dose-limiting clinical toxicities. RhIFN- is active on non-human primate cells, though not at the same level as on human cells. In addition, qualitative similarities were observed between toxicity studies employing rhIFN-gamma in the cynomolgus monkey and recombinant murine interferon-gamma (rmuIFN-gamma) in the mouse. These results suggest that in situations where a high degree of species specificity is encountered, studies employing a recombinant protein in a homologous species may provide a useful test system for preclinical safety assessment. This information should be evaluated in conjunction with data from studies conducted with the human protein in pharmacologically responsive animal models when possible.

Ischemia and ischemic preconditioning in the buffer-perfused pigeon heart. Isolated pigeon hearts were perfused with Krebs-Henseleit bicarbonate buffer with 1.25 mM Ca++ at a pressure of 60 cm H2O and paced at 210 beats per min. After an equilibration perfusion of 30 min, hearts were subjected to 10 min global ischemia and then reperfused for 30 min. Left ventricular +dP/dtmax, systolic, and end diastolic pressures differed significantly from baseline values during reperfusion as did the release of lactate dehydrogenase (LDH). When the hearts were preconditioned by interruption of flow for two 2.5-min intervals, followed by 10 min of ischemia and then reperfusion, the short periods of ischemia, followed by reperfusion, protected the hearts against the longer bout of ischemia as evidenced by significant differences between the left ventricular (LV) pressure, +dP/dtmax, LV end diastolic pressure and LDH values obtained from the hearts of control vs. preconditioned hearts. Substitution of 1 microM adenosine for the preconditioning ischemia also resulted in the preconditioning response. Ischemic preconditioning (IP) was not blocked by addition of 100 microM 8-(-p-sulfophenyl) theophylline, an adenosine receptor antagonist. Therefore, isolated, perfused bird hearts can be preconditioned, and the mechanism may involve adenosine receptors, although their activation is not necessary for i.p. to occur. Factors in addition to adenosine are likely involved.

Development of caries in permanent first molars adjacent to primary second molars with interproximal caries: four-year prospective radiographic study. This study investigated the effect of the primary second molars' distal surface caries on the incidence of the permanent first molars' mesial surface caries in 613 paired tooth surfaces of children ages 6 to 8 years at baseline examination. Proximal caries and its progression were diagnosed by bite-wing radiographs taken at a 1-year interval over a period of 4 years. The permanent first molars' mesial surfaces and primary second molars' distal surfaces were examined. Recorded were: (1) sound surfaces; (2) carious lesions on the enamel's external and internal half and on the dentin's external, middle, and internal third; (3) filled, extracted, and exfoliated teeth. The logistic model for panel data was employed to estimate the effect of proximal caries of the primary second molars' distal surfaces on the incidence of the permanent first molars' mesial surface caries. The 95% confidence interval probability was used. Sensitivity and specificity as well as the positive and negative predictive rates were computed. The results showed that the presence of proximal caries on each primary second molars' distal surfaces significantly affected the development of proximal caries on the corresponding permanent first molar's mesial surfaces. Age was estimated to exert a positive and highly significant impact, while gender had no effect. The odds ratio values ranged from 4.86 to 63.43. The values of sensitivity and specificity ranged from 45% to 97% and 80% to 89%, respectively, while the positive and negative rates ranged from 40% to 56% and 90% to 99%, respectively. Proximal caries present on the primary second molars' distal surfaces increases the risk of developing caries on the permanent first molars' mesial surfaces. This risk, however, is different among the paired surfaces studied.

Adherence in adolescents and young adults following heart or heart-lung transplantation. To assess the prevalence and some potential correlates of non-adherence to medications in adolescent and young adult transplant patients. Fifty patients who had undergone heart or heart-lung transplantation 1.4-14.9 yr (mean 8.8 yr) previously completed the Beliefs about Medication Questionnaire (BMQ), Perceived Illness Experience (PIE) scale and a demographics questionnaire. Medical notes were reviewed for information regarding previous psychiatric referral, rejection episodes and complications and noted concerns about adherence. Forty (80%) completed questionnaires were received. Non-adherence determined from the questionnaires was associated with forgetting to take medication and was classified as unintentional non-adherence. Such non-adherence was reported by 11 (28%) patients. Seven patients (18%) showed evidence from their records of deliberate non-adherence, which was classified as intentional. Whilst intentional non-adherence was associated with depression and transplant-related lymphoma, unintentional non-adherence and perceived difficulties with medications were associated with high scores on the PIE preoccupation with illness and BMQ concerns subscale and with drinking alcohol. Future research is required to determine whether unintentional non-adherence results in significant medical complications in the longer term and how a reduction in the prevalence of non-adherence can be facilitated.

Sodium selenite for treatment of Kashin-Beck disease in children: a systematic review of randomised controlled trials. To assess the effectiveness and safety of sodium selenite in treatment of patients with Kashin-Beck disease (KBD). We searched for all publications between January 1966 and October 2011 using seven electronic databases. All randomized controlled trials (RCTs) assessing the effects of sodium selenite on KBD vs no treatment or placebo were included. For dichotomous data, odds ratios (OR) and 95% confidence intervals (CI) were estimated according to the intention-to-treat principles. For continuous data, mean difference (MD) was used for outcomes pooled on the same scale. A total of 10 RCTs involving 2244 patients were included. The methodological quality of the included studies was low. When comparing the outcome of sodium selenite treatment group vs the control group, the OR of repairing rate of metaphyseal lesions was 5.63 (95% CI: 3.67-8.63) and repairing rate at the distal end of phalanges was 2.98 (95% CI: 1.32-6.70) based on X-ray assessment, which was statistically significant difference in favour of sodium selenite. In one RCT which reported data on clinical improvement, no statistically significant difference was observed in the treatment vs control group (OR 1.50, 95% CI: 0.43-5.30). Se content in hair was (MD 0.11, 95% CI: 0.09-0.13) which was statistically significant higher in selenium group. Current evidence suggests that sodium selenite is more effective than placebo or no treatment in patients with KBD. However, the evidence was limited by potential biases; thus, further high quality large-scale RCTs are still needed to evaluate the short term and long term effects of selenium.

Axonal regeneration inhibitors: emerging therapeutic options. For the most part, the central nervous system is unable to regenerate. The majority of injuries of vascular, inflammatory, degenerative and traumatic aetiology lead to an irreversible loss of central nervous system function. The paper presents the role of Nogo-A, MAG and OMgp proteins in the inhibition of central nervous system regeneration, and their potential clinical significance.

Bilateral vocal cord paralysis due to laryngeal carcinoma in Parkinson's disease. A laryngeal carcinoma presenting as severe dyspnea and stridor due to bilateral vocal cord paralysis was found in a 66-year-old man who had been suffering from Parkinson's disease (PD) for twenty years. Although laryngeal carcinoma is a common cause of bilateral vocal cord paralysis, patients with PD have been suspected to have a low cancer incidence, and this may be the first case report. Therapeutics have extended the survival of patients with PD, and the possibility of developing vocal cord paralysis. Thus, it is important for the physician to be aware that this condition may be caused by carcinoma even in PD cases.

Purification of the growth-associated protein GAP-43 by reversed phase chromatography: amino acid sequence analysis and cDNA identification. GAP-43 is a neuronal phosphoprotein. Increased synthesis and axonal transport of GAP-43 has been associated with axon growth, and altered phosphorylation of GAP-43 has been associated with changes in synaptic efficacy. Here we report a rapid and effective procedure employing reverse-phase HPLC for the purification of GAP-43 from rat brain. To characterize the protein purified by this procedure, we generated proteolytic fragments and determined their amino acid sequences. These directly determined sequences, corresponding to 56% of the GAP-43 amino acids, confirm recently reported sequences deduced from the nucleotide sequences of cDNAs. Using oligonucleotide probes constructed according to these amino acid sequences, we identified GAP-43 cDNAs in a library prepared from neonatal rat superior cervical ganglion cells. One of these cDNAs was 1.1 kB in size; it hybridized specifically with a 1.5 kB RNA from brain, but not from liver, and contained the entire coding sequence for GAP-43. This cDNA differed from recently reported cDNAs in its 3' untranslated region.

In vitro and in vivo inoculation of four endophytic bacteria on Lycopersicon esculentum. Four bacteria selected on the basis of their capability of fixing atmospheric nitrogen, stimulating plant-growth, and protecting the host plant from pathogens - Azospirillum brasilense, Gluconacetobacter diazotrophicus, Herbaspirillum seropedicae, Burkholderia ambifaria - were inoculated on tomato seeds either singularly, in couple and in a four bacteria mixer. Aim of this research was to evaluate: (1) effect of single and mixed cultures on the inoculated plant - plant growth, dry weight, root length and surface, number of leaves, among others; (2) colonization and interactions of the bacteria inside the host plant; (3) localization inside the host of single bacterial strains marked with the gusA reporter gene. The results obtained indicate that all selected microbial strains have colonized Lycopersicon esculentum but in a different way, depending on the single species. A. brasilense, G. diazotrophicus inoculated in vitro singularly and together were the best plant colonizers. In vivo essays, instead, B. ambifaria and the four-bacteria mixer gave the best results. It was possible to localize both A. brasilense and H. seropedicae inside the plant by the gusA reporter gene. The bacterial strains occur along the root axis from the apical zone until to the basal stem, on the shoot from the base up to the leaves. The four bacteria actively colonize tomato seeds and establish an endophytic community inside the plant. This review gives new information about colonization processes, in particular how bacteria interact with plants and whether they are likely to establish themselves in the plant environment after field application as biofertilizers or biocontrol agents.