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[Action of [3,14-L-selenocysteine, 8-D-tryptophan]-somatostatin on insulin and glucagon secretion of the isolated perfused pancrease of the Wistar rat]. By isolated perfused pancreas of Wistar rats the glucose (11 mmol/l) and arginine (10 mmol/l) stimulated insulin (IRI) and glucagon (IRG) secretion was measured in order to investigate the inhibitory activities of somatostatin-14 (SS 14) and the somatostatin analogue [3,14-L-seleno-cysteine, 8-D-tryptophan]-somatostatin (SeSS). SS-14 or SeSS (152.8 nmol/l) inhibit the glucose stimulated IRI secretion by 75 and 65%, respectively. Only the second phase of the biphasic arginine stimulated insulin secretion pattern by 40%. SeSS has under these conditions no effect, whereas 58 nmol/l SS-14 or SeSS show a suppressing effect on the first (20 and 55%, respectively) and second phase (65 and 85%, respectively) of the insulin secretion. Using 5.8 nmol/l SS-14 or SeSS the arginine stimulated IRG secretion was inhibited only in the second phase of the biphasic glucagon secretion pattern by about 40%. 58 nmol/l SS-14 or SeSS show an inhibiting effect on the first and on the second phase of secretion, in both cases about 50%. It is concluded that in the SS-14 molecule the sulfur of cysteine in position 3 and 14 can be exchanged by selenium without modifying the biological activities measured in the glucose or arginine stimulated IRI and IRG secretion in vitro. The D-Trp8 in the SeSS analogue does not show the typical better inhibitory action of D-Trp8-SS-14 on insulin and glucagon secretion compared with SS-14. Possibly the selenium in the SeSS analogue abolishes this effect.

Caspase-2 can trigger cytochrome C release and apoptosis from the nucleus. The cysteine proteases specific for aspartic residues, known as caspases, are localized in different subcellular compartments and play specific roles during the regulative and the executive phase of the cell death process. Here we investigated the subcellular localization of caspase-2 in healthy cells and during the execution of the apoptotic program. We have found that caspase-2 is a nuclear resident protein and that its import into the nucleus is regulated by two different nuclear localization signals. We have shown that in an early phase of apoptosis caspase-2 can trigger mitochondrial dysfunction from the nucleus without relocalizing into the cytoplasm. Release of cytochrome c occurs in the absence of overt alteration of the nuclear pores and changes of the nuclear/cytoplasmic barrier. Addition of leptomycin B, an inhibitor of nuclear export, did not interfere with the ability of caspase-2 to trigger cytochrome c release. Only during the late phase of the apoptotic process can caspase-2 relocalize in the cytoplasm, as consequence of an increase in the diffusion limits of the nuclear pores. Taken together these data indicate the existence of a nuclear/mitochondrial apoptotic pathway elicited by caspase-2.

Analysis of environmental stress response on the proteome level. Thousands of man-made chemicals are annually released into the environment by agriculture, transport, industries, and other human activities. In general, chemical analysis of environmental samples used to assess the pollution status of a specific ecosystem is complicated by the complexity of the mixture, and in some cases by the very low toxicity thresholds of chemicals present. In that sense, a proteomics approach, capable of detecting subtle changes in the level and structure of individual proteins within the whole proteome in response to the altered surroundings, has obvious applications in the field of ecotoxicology. In addition to identifying new protein biomarkers, it can also help to provide an insight into underlying mechanisms of toxicity. Despite being a comparatively new field with a number of caveats, proteomics applications have spread from microorganisms and plants to invertebrates and vertebrates, gradually becoming an established technology used in environmental research. This review article highlights recent advances in the field of environmental proteomics, mainly focusing on experimental approaches with a potential to understand toxic modes of action and to identify novel ecotoxicological biomarkers.

Cardiovascular and respiratory effects of adenosine in conscious man. Evidence for chemoreceptor activation. The cardiovascular and respiratory effects of intravenous adenosine were studied in conscious normal volunteers. Bolus injections of adenosine increased systolic and diastolic pressures initially (+15 and +13 mm Hg after 100 micrograms/kg) followed by a subsequent reduction in systolic and diastolic pressures (-12 and -16 mm Hg). Heart rate increased during trough blood pressure (R-R interval shortening of 298 msec after 100 micrograms/kg). Adenosine steady-state infusions increased heart rate (+30 beats/min during 140 micrograms/kg/min), systolic pressure (+16 mm Hg), and pulse pressure (+21 mm Hg) but decreased diastolic pressure slightly (-5 mm Hg), resulting in no significant change in mean arterial pressure. Adenosine stimulated respiration, resulting in decreased PaCO2 (41 to 31 mm Hg), increased PaCO2 (101 to 113 mm Hg), and increased pH (7.42 to 7.50). The increased ventilation was not explained by bronchoconstriction, hypotension, or hypoxia. The observed pressor and tachycardic effects are mediated through reflex autonomic mechanisms since they are completely abolished in patients with severe autonomic failure. These autonomic mechanisms probably involve chemoreceptor activation since adenosine is pressor when infused in the aortic arch proximal to the origin of the carotid arteries but depressor when infused in the descending aorta. It is concluded that the hemodynamic and respiratory effects of adenosine observed in normal volunteers are in part due to chemoreceptor stimulation. These findings raise the possibility that adenosine is an endogenous modulator of respiration in man.

Carbohydrate-derived fulvic acid is a highly promising topical agent to enhance healing of wounds infected with drug-resistant pathogens. This work was intended as a proof-of-principle study to help establish carbohydrate-derived fulvic acid (CHD-FA) as a safe and effective agent that can be deployed to prevent the onset of drug-resistant bacterial and fungal infections in military and civilian personnel experiencing traumatic wound. Minimum inhibitory concentrations for CHD-FA were established on a total of 500 clinical isolates representing wound-associated drug-sensitive and drug-resistant bacterial and fungal pathogens. The efficacy of early use of CHD-FA to enhance healing of wounds infected with methicillin-resistant Staphylococcus aureus or Pseudomonas aeruginosa was evaluated in an in vivo rat model. CHD-FA showed strong activity against a variety of bacterial and fungal pathogens with minimum inhibitory concentration values equal or less than 0.5%. Compared with infected but untreated wounds, improved wound healing upon CHD-FA treatment was observed in both infection models, demonstrated by wound surface area measurement, histopathologic examination, and expression profiling of wound healing genes. Up-regulation of proinflammatory cytokine interleukin 6 (IL-6) at Day 3 after infection was significantly dampened at Days 6 and 10 in the CHD-FA-treated wounds in both infection models, displaying an improved and accelerated wound healing. CHD-FA is a promising topical remedy for drug-resistant wound infections. It accelerated the healing process of wounds infected with methicillin-resistant S. aureus and multidrug-resistant P. aeruginosa in rats, which is linked to both its antimicrobial and anti-inflammatory properties.

Aortic arch morphogenesis and flow modeling in the chick embryo. Morphogenesis of the "immature symmetric embryonic aortic arches" into the "mature and asymmetric aortic arches" involves a delicate sequence of cell and tissue migration, proliferation, and remodeling within an active biomechanical environment. Both patient-derived and experimental animal model data support a significant role for biomechanical forces during arch development. The objective of the present study is to quantify changes in geometry, blood flow, and shear stress patterns (WSS) during a period of normal arch morphogenesis. Composite three-dimensional (3D) models of the chick embryo aortic arches were generated at the Hamburger-Hamilton (HH) developmental stages HH18 and HH24 using fluorescent dye injection, micro-CT, Doppler velocity recordings, and pulsatile subject-specific computational fluid dynamics (CFD). India ink and fluorescent dyes were injected into the embryonic ventricle or atrium to visualize right or left aortic arch morphologies and flows. 3D morphology of the developing great vessels was obtained from polymeric casting followed by micro-CT scan. Inlet aortic arch flow and cerebral-to-lower body flow split was obtained from 20 MHz pulsed Doppler velocity measurements and literature data. Statistically significant variations of the individual arch diameters along the developmental timeline are reported and correlated with WSS calculations from CFD. CFD simulations quantified pulsatile blood flow distribution from the outflow tract through the aortic arches at stages HH18 and HH24. Flow perfusion to all three arch pairs are correlated with the in vivo observations of common pharyngeal arch defect progression. The complex spatial WSS and velocity distributions in the early embryonic aortic arches shifted between stages HH18 and HH24, consistent with increased flow velocities and altered anatomy. The highest values for WSS were noted at sites of narrowest arch diameters. Altered flow and WSS within individual arches could be simulated using altered distributions of inlet flow streams. Thus, inlet flow stream distributions, 3D aortic sac and aortic arch geometries, and local vascular biologic responses to spatial variations in WSS are all likely to be important in the regulation of arch morphogenesis.

Do dogs resemble their owners? We examined whether the frequent casual reports of people resembling their pets are accurate by having observers attempt to match dogs with their owners. We further explored whether any ability of observers to make such matches is due to people selecting dogs who resemble them, in which case the resemblance should be greater for predictable purebreds than for nonpurebreds, or is due to convergence, in which case the resemblance should grow with duration of ownership. Forty-five dogs and their owners were photographed separately, and judges were shown one owner, that owner's dog, and one other dog, with the task of picking out the true match. The results were consistent with a selection account: Observers were able to match only purebred dogs with their owners, and there was no relation between the ability to pair a person with his or her pet and the time they had cohabited. The ability to match people and pets did not seem to rely on any simple trait matching (e.g., size or hairiness). The results suggest that when people pick a pet, they seek one that, at some level, resembles them, and when they get a purebred, they get what they want.

Enzymatic biosynthesis of cyclosporin A and analogues. The final assembly of the undecapeptide chain of cyclosporin A and its cyclization is accomplished in Beauveria nivea by cyclosporin synthetase. This multienzyme is the largest integrated enzyme structure so far reported. Its size has been estimated at approximately 1,400 kDa by two different methods: 1), by 3% SDS-PAGE using the related multienzymes ACV synthetase and gramicidin S synthetase 2 as references (420 and 556 kDa, respectively); and 2), by CsCl density gradient centrifugation experiments using fluorescence-labeled cyclosporin synthetase. Besides cyclosporin A and a number of cyclosporins known from fermentation studies cyclosporin synthetase is capable of synthesizing some new cyclosporins which are so far unobtainable by fermentation. So, for example the synthesis of [N-methyl-(+)-2-amino-3-hydroxy-4,4-dimethyloctanoic acid1]CyA, dihydro-CyA, [L-norvaline2,5, N-methyl-L-norvaline11]CyA, [L-allo-isoleucine5, N-methyl-L-allo-isoleucine11]CyA, [D-2-aminobutyric acid8]CyA, [beta-chloro-D-alanine8]CyA and some related compounds could be established. By using a related but different enzyme from Cylindrotrichum Bonorden, the peptolide [L-threonine2, L-leucine5,10, D-2-hydroxyisovaleric acid8]CyA could be synthesized in vitro. We were able to synthesize these cyclosporins in sufficient quantities to examine their structure by FAB mass spectroscopy and explore their immunosuppressivity. It was found that all new cyclosporins so far synthesized in the in vitro system are immunosuppressive.

Pressure infusors: variability in delivered infusion pressure. A pressure infusor was used to apply external pressures of 300, 250, 200, and 150 mm Hg to 500-ml plastic bags of saline. At constant applied pressure, 50-ml aliquots of saline were periodically withdrawn. The delivered pressures were less than the applied pressures, and the difference increased as the volume of saline within the bag decreased. This inherent pressure difference should be considered when the system is used with a continuous flush device.

Double second toe transfer in congenital hand anomalies. A series of 14 patients with congenital hand anomalies who received staged double second toe transfers to the same hand for restoration of function or form were reviewed retrospectively. There were three children with constriction ring syndrome, two with symbrachydactyly and nine with transverse absence (failure of formation). There were different indications, technical difficulties and results with the various anomalies. All transferred toes were mobile and sensate, and were reported to be of benefit in both function and appearance. However, secondary surgical procedures were required in all patients.

Peroxisome proliferator-activated receptor alpha induces NADPH oxidase activity in macrophages, leading to the generation of LDL with PPAR-alpha activation properties. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors controlling lipid and glucose metabolism as well as inflammation. PPARs are expressed in macrophages, cells that also generate reactive oxygen species (ROS). In this study, we investigated whether PPARs regulate ROS production in macrophages. Different PPAR-alpha, but not PPAR-gamma agonists, increased the production of ROS (H2O2 and ) in human and murine macrophages. PPAR-alpha activation did not induce cellular toxicity, but significantly decreased intracellular glutathione levels. The increase in ROS production was not attributable to inherent prooxidant effects of the PPAR-alpha agonists tested, but was mediated by PPAR-alpha, because the effects were lost in bone marrow-derived macrophages from PPAR-alpha-/- mice. The PPAR-alpha-induced increase in ROS was attributable to the induction of NADPH oxidase, because (1) preincubation with the NADPH oxidase inhibitor diphenyleneiodinium prevented the increase in ROS production; (2) PPAR-alpha agonists increased production measured by superoxide dismutase-inhibitable cytochrome c reduction; (3) PPAR-alpha agonists induced mRNA levels of the NADPH oxidase subunits p47(phox), p67phox, and gp91phox and membrane p47phox protein levels; and (4) induction of ROS production was abolished in p47phox-/- and gp91phox-/- macrophages. Finally, induction of NADPH oxidase by PPAR-alpha agonists resulted in the formation of oxidized LDL metabolites that exert PPAR-alpha-independent proinflammatory and PPAR-alpha-dependent decrease of lipopolysaccharide-induced inducible nitric oxide synthase expression in macrophages. These data identify a novel mechanism of autogeneration of endogenous PPAR-alpha ligands via stimulation of NADPH oxidase activity.

Development of polymeric microbubbles targeted to prostate-specific membrane antigen as prototype of novel ultrasound contrast agents. Ultrasound-targeted microbubbles (MBs) offer new opportunities to enhance the capabilities of diagnostic ultrasound (US) imaging to specific pathological tissue. Herein, we report on the design and development of a novel prototype of US contrast agent based on polymeric MBs targeted to prostate-specific membrane antigen (PSMA) for use in the diagnosis of prostate cancer (PCa). First, a set of air-filled MBs by a variety of biocompatible polymers were prepared and characterized in terms of morphology and echogenic properties after exposure to US. MBs derived from poly(D,L-lactic-co-glycolic acid) (PLGA)-poly(ethylene glycol) (PEG) copolymer resulted as the most effective in terms of reflectivity. Such polymer was therefore preconjugated with a urea-based PSMA inhibitor molecular probe (DCL), and the obtained MBs were investigated in vitro for their targeting efficacy toward PSMA positive PCa (LNCaP) cells. Fluorescence microscopy proved a specific and efficient adhesion of targeted MBs to LNCaP cells. To our knowledge, this work reports the first model of polymeric MBs appropriately engineered to target PSMA, which might be further optimized and used for PCa diagnosis and potential carriers for selective drug delivery.

[Analysis of microsurgical reconstruction activity in a university hospital: A 14-year historical cohort]. Each university hospital has its own specificities in microsurgical reconstructions. Activities may focus on breast reconstruction, ENT reconstruction or traumatic substance loss. This study analyzes the specificities at the University Hospital of Nancy, studies the indications, the operating data and the failure rates. We realized a historical cohort of microsurgical reconstructions at Nancy University Hospital from January 1, 2004 to December 31, 2017. All free flaps were included and analyzed. A total of 359 free flaps were made. The failure rate was 9.47%. Forty eight different operators have been identified. Substance losses were essentially traumatic (56.8%). A total of 20 different flaps were use with 49% bone reconstruction. The fibula flap was the first flap used (26.5%). Arterial anastomoses were performed in termino-lateral in 44% and venous anastomoses were single in 70.5%. High BMI, diabetes, high blood pressure, atherosclerosis, and arterial or venous graft were identified as risk factors for failure (P<0.05). The smoking and the realisation of the intervention by a young operator have no impact on the success rate. Our specificity is the bone reconstruction which represents a significant part of our activity. In the university center, the number of etiology of substance losses, operator and flap used is important but it still allows to obtain results in adequacy with the literature.

Relationship between sagittal spinal alignment and the incidence of vertebral fracture in menopausal women with osteoporosis: a multicenter longitudinal follow-up study. To investigate the relationship between sagittal spinal alignment and the incidence of vertebral fracture in patients with osteoporosis. A cohort of 1,044 postmenopausal women with osteoporosis were prospectively observed for the incidence of lumbar vertebral fracture. Baseline characteristics of the subjects were recorded, including age, year post-menopause, body height and weight, lumbar spine BMD (LSBMD) and femoral neck BMD (FNBMD). Patients with radiologically diagnosed lumbar vertebral fractures were assigned to the fracture group, and 150 randomly selected participants were assigned to the non-fracture group. Parameters depicting sagittal spinal alignment, including sacral slope (SS), pelvic tilt, pelvic incidence (PI), thoracic kyphpsis, lumbar lordosis (LL), lumbar lordosis index (LLI) and sagittal vertical axis, were measured for both groups. Comparison between the two groups was carried out by Student's t test. Variables showing significant differences were entered into a logistic regression analysis to determine the independent risk factors. Patients with fracture events had significantly lower LSBMD as well as a significantly longer year post-menopause. Besides, patients with vertebral fracture were found to have significantly lower LL, LLI, SS and PI. Regression analysis showed that LSBMD (OR = 0.27), LL (OR = 0.3), LLI (OR = 0.43) and PI (OR = 0.67) had significant associations with the risk of vertebral fracture. Osteoporosis patients with low LL, LLI, and PI could be at high risk of lumbar vertebral fracture. In addition to BMD, the abnormal sagittal spinal profile should also be taken into consideration when predicting the incidence of vertebral fracture in such patients.

A Percutaneous Transtubular Middle Fossa Approach for Intracanalicular Tumors. In cases of small intracanalicular tumors (≤ 1.5 cm), the middle fossa approach (MFA) provides the ability for adequate tumor removal with preservation of existing auditory function. Application of a minimally invasive tubular retractor in this approach may help mitigate the risk of postoperative seizures, aphasia, and venous complications by minimizing intraoperative retraction of the temporal lobe. We propose a minimally invasive microscopic and/or endoscopic percutaneous transtubular MFA for the management of intracanalicular tumors. Subtemporal keyhole craniectomies were performed on 5 preserved cadaveric heads (10 sides), with 6 sides previously injected with a synthetic tumor model. A ViewSite Brain Access System tubular retractor (Vycor Medical, Inc., Boca Raton, Florida, USA) was used to provide minimal temporal retraction and protection of the surrounding anatomy. An extradural dissection of the internal auditory canal was performed under microscopic and endoscopic visualization with a minimally invasive surgical drill and tube shaft instruments, the intracanalicular tumors were removed, and degree of resection was assessed. All 10 approaches were completed successfully through the tubular retractor with minimal retraction of the temporal lobe. Excellent visualization of the structures within the internal auditory canal was achieved with both the microscope and 3-dimensional endoscope. On the 6 synthetic intracanalicular tumors resected, 5 gross total (Grade I) and 1 near total (Grade II) resections were achieved. A percutaneous transtubular MFA is a feasible minimally invasive option for resection of small intracanalicular tumors with potential preservation of auditory function, reduced temporal retraction, and enhanced protection of surrounding structures.

[Hereditary and non-hereditary cutaneous amyloidoses]. Amyloid and amyloidosis describes a heterogeneous group of diseases which are characterized by the pathological extracellular deposition of autologous proteins. Basically, amyloidoses can be divided into systemic or organ-limited (e.g. cutaneous) forms and can be acquired or hereditary in nature. The subclassification discriminates between primary amyloidosis (in the absence of an obvious predisposing disease) and secondary amyloidosis (if caused by a certain underlying disease). The subclassification of amyloidoses is based on the main protein constituent and therefore on the chemical composition of the amyloid fibrils. However, the exact etiopathogenesis of amyloid formation remains unclear. In addition to the clinical presentation, histology, electron microscopy and biochemical-immunological differentiation are also decisive for a proper diagnosis. In cutaneous amyloidosis the deposition of amyloid either occurs along reticulin fibers and the basal membrane (perireticulary amyloidoses) or along collagen fibers (pericollagenous amyloidosis). The purpose of this article is to provide an up-to-date overview on the different kinds of cutaneous amyloidoses.

Establishment of monoclonal antibodies specific for Bacillus subtilis DB9011. Bacillus subtilis DB9011 is a strain with useful functions for agriculture. To establish a method for the discrimination of this strain from others, monoclonal antibodies (MAbs) were prepared. Although two established MAbs (MAb9B6 and MAb14D2) cross-react with some other Bacillus strains in ELISA, only B. subtilis DB9011 vegetative cells are recognized by both MAbs. MAb14D2 recognizes flagellin, a 34-kDa unit protein of flagella. The two MAbs established will provide powerful tools with which detailed analysis of this bacterial strain can be obtained under environmental conditions.

QTL and candidate genes phytoene synthase and zeta-carotene desaturase associated with the accumulation of carotenoids in maize. Carotenoids are a class of fat-soluble antioxidant vitamin compounds present in maize ( Zea mays L.) that may provide health benefits to animals or humans. Four carotenoid compounds are predominant in maize grain: beta-carotene, beta-cryptoxanthin, zeaxanthin, and lutein. Although beta-carotene has the highest pro-vitamin A activity, it is present in a relatively low concentration in maize kernels. We set out to identify quantitative trait loci (QTL) affecting carotenoid accumulation in maize kernels. Two sets of segregating families were evaluated-a set of F2:3 lines derived from a cross of W64a x A632, and their testcross progeny with AE335. Molecular markers were evaluated on the F2:3 lines and a genetic linkage map created. High-performance liquid chromatography was performed to measure beta-carotene, beta-cryptoxanthin, zeaxanthin, and lutein on both sets of materials. Composite interval mapping identified chromosome regions with QTL for one or more individual carotenoids in the per se and testcross progenies. Notably QTL in the per se population map to regions with candidate genes, yellow 1 and viviparous 9, which may be responsible for quantitative variation in carotenoids. The yellow 1 gene maps to chromosome six and is associated with phytoene synthase, the enzyme catalyzing the first dedicated step in the carotenoid biosynthetic pathway. The viviparous 9 gene maps to chromosome seven and is associated with zeta-carotene desaturase, an enzyme catalyzing an early step in the carotenoid biosynthetic pathway. If the QTL identified in this study are confirmed, particularly those associated with candidates genes, they could be used in an efficient marker-assisted selection program to facilitate increasing levels of carotenoids in maize grain.

The influence of sex on patients with rheumatoid arthritis in a large observational cohort. To compare the sex differences of various components of rheumatoid arthritis (RA). Data of 4823 patients from a large observational cohort study were analyzed. Remarkable differences were noted between the sexes, and overall, women had significantly higher disease activity. When variables were adjusted using sex, age, and duration, Health Assessment Questionnaire, rather than Disease Activity Score, contributed most to sex difference. Further analysis showed evidence that progression of disability was approximately 3 times more rapid in female patients compared to male patients. Women overall have higher RA disease activity and are prone to greater and faster progression of disability over time.

Stem cell factor and high-dose twice daily filgrastim is an effective strategy for peripheral blood stem cell mobilization in patients with indolent lymphoproliferative disorders previously treated with fludarabine: results of a Phase II study with an historical comparator. Fludarabine exposure leads to impaired peripheral blood stem cell (PBSC) mobilization in indolent lymphoproliferative disorders (LPD). We previously reported that only 34% of fludarabine-exposed patients mobilized successfully using granulocyte-colony stimulating factor (G-CSF; median 10 microg/kg/day) with or without chemotherapy, with unpredictable kinetics and moderate infectious morbidity. Stem cell factor (SCF) plus high-dose twice daily (b.d.) G-CSF may improve mobilization in these patients. SCF 20 microg/kg/day subcutaneously was given from day 1, G-CSF 12 microg/kg b.d. subcutaneously from day 4, apheresis commenced from day 6. Previous study patients served as historical controls. Thirty five patients with indolent LPD were enrolled, median age was 54 years (range 31-66), 66% male, median cumulative prior fludarabine dose was 660 (405-900) mg. Overall, 22 patients (63%) collected >or= 2.0 x 10(6)/kg PBSC (success), compared to 34% controls (odds ratio (OR) 3.2; 95% confidence interval (CI) (1.2, 9.3); P=0.021). Median CD34(+) yield overall was 2.3 x 10(6)/kg (0.53-8.97) from median four (2-6) aphereses. Study patients >or= 50 years mobilized successfully more frequently than controls (58 versus 17%; P=0.0065). Adjusting for age, successful mobilization remained significantly higher in the current study (OR 4.2; 95% CI (1.4, 14.0); P=0.008). SCF/high-dose b.d. G-CSF improves PBSC mobilization efficacy after fludarabine exposure, over mobilization using G-CSF as the mobilizing cytokine. This combined growth factor strategy is a preferred mobilization method for fludarabine-exposed patients.

Assessment of heavy metals and arsenic pollution in surface sediments from rivers around a uranium mining area in East China. Taking the surface sediments of rivers near a uranium mine in East China as the research object, the concentrations of seven metals, including Cr, Cu, Ni, Pb, Zn, Cd and As, were analyzed. The pollution degree and ecological risk of heavy metals and arsenic were evaluated according to the geo-accumulation index, pollution loading index, potential ecological risk index and sediment quality guidelines. Finally, the sources of pollution were determined by Pearson's correlation analysis, principal component analysis and hierarchical cluster analysis. The results indicated that Cr, Cu, Ni, Pb, Zn, Cd and As in sediments showed varying degrees of contamination, using the soil background value of the study area as a reference, and Cd was the main excessive pollutant in the sediments. In most parts of the river, Cd has reached a moderate level of pollution. The potential ecological hazards at sampling sites 9, 13, 17 and 18 are significantly higher than the other sites because of the impact of urbanization and uranium mining and smelting. Cu, Zn, Cr, Ni and Cd are mainly derived from urban activities and the uranium industry, Pb is mainly derived from vehicle emissions, and As is mainly derived from nature and rocks.

Policy aspects and nursing care of families with parents who are sexual minorities. Families in which parents are lesbian, gay, bisexual, or transgender are more diverse than they are similar. This article reviews current literature to identify fundamental issues facing families that include sexual minority parents and their children. The unique nursing needs of families with gay, lesbian, transgender, or bisexual parents are critically examined for direct relevance to family nursing practice. Nurses and other health care professionals can incorporate current knowledge of unique child developmental, parenting, and legal issues into their work with these families. Nursing assessment and policies that consider the unique needs of these families will be addressed.

Does greed help a forager survive? We investigate the role of greed on the lifetime of a random-walking forager on an initially resource-rich lattice. Whenever the forager lands on a food-containing site, all the food there is eaten and the forager can hop S more steps without food before starving. Upon reaching an empty site, the forager comes one time unit closer to starvation. The forager is also greedy-given a choice to move to an empty or to a food-containing site in its local neighborhood, the forager moves preferentially toward food. Surprisingly, the forager lifetime varies nonmonotonically with greed, with different senses of the nonmonotonicity in one and two dimensions. Also unexpectedly, the forager lifetime in one dimension has a huge peak for very negative greed where the forager is food averse.

The effects of dietary fat and selenium on the development of preneoplastic lesions in rat liver. In this study, the effects of dietary fat and selenium on the development of putative preneoplastic foci induced by aflatoxin B1 were examined. Rat hepatic gamma-glutamyl transpeptidase (GGT) activity, selenium-dependent glutathione peroxidase activity, glutathione, and total lipid were analyzed 3 and 13 weeks after the start of dietary and carcinogen treatment. Results indicate that high dietary fat has an enhancing effect on the development of preneoplastic foci. A high-fat, selenium-deficient diet resulted in an increase in foci development, but the increase was not significant. An interaction between aflatoxin and the two nutrients was also observed in liver glutathione content and GGT activity at Week 3.

Investigation of hemophagocytic lymphohistiocytosis in severe sepsis patients. Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition characterized by uncontrolled inflammation and has common clinical and laboratory features with sepsis. The aim of this study was to investigate patients treated with severe sepsis who had bicytopenia for the presence of HLH. Patients with severe sepsis who were non-responsive to treatment and developed at least bicytopenia were included. Peripheral blood samples were collected and stored for later evaluation for natural killer (NK) activity and soluble interleukin-2 receptor levels. Diagnostic criteria of HLH were retrospectively analyzed. Seventy-five of 382 patients (20%) were followed as severe sepsis and septic shock. Among them, 40 patients had bicytopenia. Twenty-six of 40 patients were excluded due to the presence of active solid or hematological malignancies. Three patients died before fulfillment of HLH criteria and one patient denied to give consent. All of the remaining 10 patients had at least five of the eight criteria according to criteria of the Histiocyte Society. Only one of 10 patients was diagnosed as HLH and received treatment during intensive care unit stay. None of the 10 patients survived. This study emphasizes to consider the possibility of HLH and the need of rapid assessment of patients with severe sepsis who had bicytopenia and were resistant to treatment in intensive care.

Subsurface characterization of methane production and oxidation from a New Hampshire wetland. We measured the carbon isotopic composition of pore water carbon dioxide from Sallie's Fen, a New Hampshire poor fen. The isotope profiles are used in combination with a one-dimensional diffusion-reaction model to calculate rates of methane production, oxidation and transport over an annual cycle. We show how the rates vary with depth over a seasonal cycle, with methane produced deeper during the winter months and at progressively shallower depths into the summer season. The rates of methane production, constrained by the measured delta(13)C(dic) profiles, cannot explain high methane emission during the summer. We suggest that much of the methane produced during this time comes either from the unsaturated peat, or from the top 1-3 cm of saturated peat where episodic exchange with the atmosphere makes it invisible to our method.

[Changes in the renal corpuscles during early postnatal ontogeny of the rat (stereologic analysis)]. Kidneys of 60 white rats at the age of 1-45 days of postnatal life have been investigated. Increase in size of the renal corpuscles during the developmental process is accompanied with certain changes in the form and variability of volumes in the structures studied. During early postnatal period, against the background of linear increase in the size of the renal corpuscles, the parameters of variability in volumes, form and in the total number of the renal corpuscles in the organ change non-linear. Stabilization moment of the total number (11-14 days) on the 8th-10th day outgoes that for the parameters of the form and variability of the renal corpuscle volumes.

Scale to measure patient satisfaction with physical therapy. Patient satisfaction can be one indicator of quality of care. In this study, a patient satisfaction questionnaire for physical therapy was developed. The subjects were a consecutive sample of 1,024 patients who received physical therapy between January and March 1999 at a teaching hospital in Geneva, Switzerland. A cross-sectional mail survey was conducted in which a structured questionnaire measuring patient satisfaction with various aspects of physical therapy followed by open-ended questions was sent to the subjects. Overall, 528 of 1,024 patients (52%) responded (patient demographics for 501 respondents who provided demographic data: mean years of age=58.6, SD=18.9, range=15-95; 258 men, 243 women). Factor analysis was used to identify main domains of satisfaction, and a scale was constructed to measure satisfaction with each dimension: treatment subscale (5 items), admission subscale (3 items), logistics subscale (4 items), and a global assessment subscale (2 items). All subscales had good acceptability and small floor and ceiling effects. Internal consistency coefficients varied between.77 and.90, indicating good reliability for all subscales. Scale validity was supported by a logical grouping of items into subscales, according to their content, and by correlations of satisfaction scores with the patient's intention to recommend the facility and with the number of positive and negative comments to open-ended questions. Younger patients were less satisfied than older patients for 2 of the subscales (admission and logistics). The 14-item instrument is a promising tool for the evaluation of patient satisfaction with physical therapy in both inpatients and outpatients.

Malignant lympho-epithelial lesion of the salivary gland: a case report and review of the literature. Malignant lympho-epithelial lesion of the salivary gland is an undifferentiated squamous cell carcinoma which is associated with a prominent lymphocyte-rich stroma. This study reviews the current literature pertaining to this rare tumour with reference to the single recorded case of malignant lympho-epithelial lesion of the salivary gland presenting in Auckland, New Zealand. This 26 year old Caucasian male developed a rapidly growing lesion in the right parotid gland and multiple ipsilateral cervical lymph nodes. Treatment consisted of surgery and radiotherapy. The patients is currently disease free. One hundred and eight other cases have been reported in the literature, 82 of whom have Mongolian ancestry (Eskimos and southern Chinese) and 15 of whom are Caucasian. More than 50% of these patients (all Mongolian) have elevated titres of serum immunoglobulin A against Epstein-Barr virus capsid antigen. The age at presentation is variable, ranging from 10 to 86 years, with a slight female predominance. Forty-one per cent of patients present with regional lymph node metastases and 20% with distant metastases. Given the rarity of this disease, treatment is controversial. Current data suggest that early radical combined modality treatment using surgery and radiotherapy leads to prolonged survival and cure with 5 year survival rates greater than 50%.

[Prevention of acute hypertensive encephalopathy in the course of acute post-streptococcal glomerulonephritis in children: considerations in 31 cases]. The authors analysed 31 cases of an acute hypertensive glomerulonephritis. The antihypertensive efficacy of two medicines: a vasodilator (dihidralazine) and a diuretic (Furosemide) was underlibed an these patients. Their efficacy was evident not only in the stabilization of P.A. around normal values on three days, but also on the disappearance of signs of on hypertensive encephalopathy whereas these ones were present.

[Defibrillation efficacy of a newly developed automated external defibrillator in a swine ventricular tachycardia/fibrillation model]. The aim of this study was to evaluate the recognition and defibrillation efficiency of a newly developed automated external defibrillator (AED). Ventricular tachycardia (VT)/ventricular fibrillation (VF) was induced by alternating current (50 Hz) through an electrode placed on apex of right ventricle in 23 anesthetized swine and recorded, recognized and defibrillated by a newly developed AED. A total of 96 VF was induced and 145 defibrillations were recorded. We analyzed available 167 electrocardiosignal with a total length of 103,740 seconds. The accuracy, sensitivity and the specificity of the AED on VT/VF recognition are 99.5%, 98.2% and 99.6%, respectively. The success rate of defibrillation was 33.4% which increased in proportion to defibrillation energy. The defibrillation threshold of energy is 29.10-116.91 (78.75 +/- 35.64) J, the defibrillation threshold of electric quantity is (0.11 +/- 0.04) C and the defibrillation threshold of voltage is (1216.67 +/- 260.87) V. This newly developed AED has high sensitivity and the specificity on recognizing VT/VF. The lower success rate of defibrillation of this AED is associated with the low defibrillation energy during defibrillation which needs to be improved on further development.

Comparison of 1 vs 2 or more intracavitary brachytherapy applications in the management of carcinoma of the cervix, with irradiation alone. Four hundred ninety-eight patients treated in the USA in 1978 for cancer of the cervix by external beam and intracavitary irradiation have been studied to determine the effect of using a single intracavitary (IC) application versus more than one. Most of the patients (46%) underwent intracavitary (IC) treatment after external radiation therapy (RT), 40% during external RT, and 14% prior to external RT. Five-year actuarial survival for all stages was 66% for greater than or equal to 2 applications versus 59% for 1 application, p less than .01. When survival was analyzed by stage, there was a trend toward improved survival with greater than or equal to 2 applications in Stage II (p .10). The rate of infield recurrence for all stages was higher in the 1 IC group (30% vs 17%, p less than .01). These were more frequent in the 1 IC group (53% vs 34%, p less than .05), in Stage III patients, but no significant difference was noted in the other stages. Distant metastases were more frequent in the 1 IC group (19% vs 11%, p .01). The incidence of major complications was the same in both groups. An analysis of patient characteristics and other variables that would explain the difference in results revealed that older patients (p .03), worse Karnofsky (p .056), and more parametrial involvement (p less than .01) accrued more in the 1 IC group. Higher paracentral point doses were administered when greater than or equal to 2 IC applications were used (p less than 0.01); this group also received higher bladder and rectal doses and lower whole pelvic doses. The use of two or more intracavitary insertions affords an opportunity to administer higher paracentral point doses, which appear to be related to higher pelvic tumor control, lower rate of distant metastasis, and better survival.

Application of the NMR-MOUSE to food emulsions. The application of the NMR-MObile Universal Surface Explorer (NMR-MOUSE) to study food systems is evaluated using oil-in-water emulsions, and the results are compared to those obtained using a conventional low-field NMR (LF-NMR) instrument. The NMR-MOUSE is a small and portable LF-NMR system with a one-sided magnet layout that is used to replace the conventional magnet and probe on a LF-NMR instrument. The high magnetic field gradients associated with the one-sided MOUSE magnet result in NMR signal decays being dominated by molecular diffusion effects, which makes it possible to discriminate between the NMR signals from oil and water. Different data acquisition parameters as well as different approaches to the analysis of the NMR data from a range of oil-in-water emulsions are evaluated, and it is demonstrated how the concentration of oil and water can be determined from the NMR-MOUSE signals. From these model systems it is concluded that the NMR-MOUSE has good potential for the quantitative analysis of intact food products.

Association of induction of a fully tumorigenic phenotype in murine radiation-induced T-lymphoma cells with loss of differentiation antigens, gain of CD44, and alterations in p53 protein levels. We investigated the mechanism of radiation induction of murine thymic lymphomas by studying the characteristics of primary x-ray-induced thymic lymphoma (PXTL) cell lines and of their oncogene-induced, progressed progeny. It is widely thought that proto-oncogene alterations are associated with the induction of murine lymphomas; however, few, if any primary murine radiation-induced lymphomas possess (proto-)oncogene alterations. Independently derived cell lines grown directly (i.e., without in vivo transplantation) from thymic lymphomas of irradiated C57BL/6 mice possess the properties of immortalized pre-T cells and lack many of the characteristics of "tumor cells". PXTL cells are poorly tumorigenic upon transplantation, do not clone in methylcellulose cultures, are growth factor dependent and autocrine, and lack consistent chromosome and oncogene abnormalities. However, the thymic lymphomas are malignant and cause the death of each afflicted mouse. PXTL cells expressed two immunologically distinct forms of the tumor suppressor protein p53 that have moderately increased stability (t1/2 = 1 h) when compared with p53 of normal splenic T lymphocytes. Early PXTL cells could progress in vitro to a fully tumorigenic phenotype after infection with retroviruses encoding the c-myc and v-ras oncogenes. Progressed T-lymphoma cells acquired growth factor independence, a highly transplantable and tumorigenic phenotype, and the ability to quantitatively clone in methylcellulose cultures. Progressed lymphoma cells coordinately downregulated the expression of five T-cell differentiation markers, upregulated the expression of CD44 (Pgp-1), and harbored vastly elevated levels of two immunologically distinct forms of p53. Our results suggest that the early thymic lymphomas consist of differentiation-inhibited, immortal pre-T cells that are precursors to progressed, fully tumorigenic T-lymphoma cells.

[Study on malaria vectors in malaria endemic areas of Tibet autonomous region]. The malaria situation in Tibet has been in an active status and the malaria incidence reached the second in China in 2010. Malaria vector prevention and control is one of the important methods for malaria control, while the malaria vectors are still unknown in Tibet. The author summarized the past researches on malaria vectors in Tibet, so as to provide the evidence for improving malaria control investigation in malaria endemic areas of Tibet, with hopes to provide useful vector message for other researcher.

Gelatinases A and B and tissue inhibitors of metalloproteinases 1, 2, and 3 during in vivo and in vitro decidualization of rat endometrial stromal cells. An important event during decidualization is the remodeling of the extracellular matrix, an event controlled by the balance of matrix metalloproteinases and tissue inhibitors of metalloproteinases (TIMPs). A putative regulator of decidualization is prostaglandin E2 (PGE2). The present study shows that endometrial mRNA levels for TIMPs 1, 2, and 3 were increased while gelatinase A levels remained unchanged and gelatinase B levels decreased during oil-induced decidualization. The production of TIMPs 1, 2, and 3 and gelatinases A and B during in vitro decidualization was examined, as was the role of PGE2 as a regulator. Ovariectomized rats were given a regimen of estrogen and progesterone, which sensitized their uteri for decidualization, at which time endometrial stromal cells were isolated and cultured in serum-free conditions for 72 h. Northern blot analyses indicated the presence of the mRNAs for TIMPs and gelatinases, while reverse zymography and zymography showed the presence of their proteins. PGE2 decreased mRNA levels for TIMP-1 and gelatinase A but had no effect on gelatinase B or TIMPs 2 and 3. Indomethacin had no effect on any of the transcripts. These data indicate that rat endometrial stromal cells undergoing decidualization in vitro secrete gelatinases and TIMPs, and suggest that PGE2 may play a role in regulating tissue remodeling during decidualization.

[Microcirculation in patients with systemic scleroderma during treatment using hyperbaric oxygenation]. Hyperbaric oxygenation treatment of systemic scleroderma has a favourable effect on microcirculatory changes whose positive dynamics can be demonstrated by conjunctival biomicroscopy. These changes include accelerated blood flow and decrease in the degree of erythrocyte aggregation. The method can be used for the objective assessment and for prognosis of the effectiveness of hyperbaric oxygenation treatment in patients with systemic scleroderma.

Skin pathology induced by snake venom metalloproteinase: acute damage, revascularization, and re-epithelization in a mouse ear model. Viperid snakebite envenomation induces blistering and dermonecrosis. The pathological alterations induced by a snake venom metalloproteinase in the skin were investigated in a mouse ear model. Metalloproteinase BaP1, from Bothrops asper, induced rapid edema, hemorrhage, and blistering; the latter two effects were abrogated by preincubation with the metalloproteinase inhibitor batimastat. Neutrophils did not play a role in the pathology, as depletion of these cells resulted in a similar histological picture. Blisters are likely to result from the direct proteolytic activity of BaP1 of proteins at the dermal-epidermal junction, probably at the lamina lucida, as revealed by immunostaining for type IV collagen and laminin. Widespread apoptosis of keratinocytes was detected by the TUNEL assay, whereas no apoptosis of capillary endothelial cells was observed. BaP1 induced a drastic reduction in the microvessel density, revealed by immunostaining for the endothelial marker vascular endothelial growth factor receptor-2. This was followed by a rapid angiogenic response, leading to a partial revascularization. Skin damage was followed by inflammation and granulation tissue formation. Then, a successful re-epithelization process occurred, and the skin of the ear regained its normal structure by 2 weeks. Venom metalloproteinase-induced skin damage reproduces the pathological changes described in snakebitten patients.

3D-QSAR CoMFA on cyclin-dependent kinase inhibitors. Several series of cyclin-dependent kinase inhibitors previously prepared in our laboratory were compared using 3D-QSAR (CDK1) and docking (CDK2) techniques. Evaluation of our own library of 93 purine derivatives served to establish the model which was validated by evaluation of an external library of 71 compounds. The best predictions were obtained with the CoMFA standard model (q(2) = 0.68, r(2) = 0.90) and with the CoMSIA combined steric, electrostatic, and lipophilic fields (q(2) = 0.74, r(2) = 0.90). The CDK1 3D-QSAR model was then superimposed to the ATP/CDK2 binding site, giving direct contour maps of the different fields. Although too few compounds were evaluated on CDK5 to derive a 3D-QSAR model, some interesting SARs have been deduced. Comparison of the results obtained from both methods helped with understanding the specific activity of some compounds and designing new specific CDK inhibitors.

Kibdelosporangium lantanae sp. nov., isolated from the rhizosphere soil of an ornamental plant, Lantana camara L. Strain XMU 506T, isolated from the rhizosphere soil of an ornamental plant, Lantana camara L., collected from Xiamen City, China, was identified using a polyphasic approach to clarify its taxonomic position. The aerial mycelium of this organism formed long straight or curved chains of spores and sporangium-like structures. The optimum growth occurred at 28-30 °C, pH 7.0 with 0-1% NaCl. Strain XMU 506T showed the highest 16S rRNA gene sequence similarity (96.5%) to Kibdelosporangium philippinense DSM 44226T, and formed a monophyletic clade in the 16S rRNA gene phylogenetic tree together with the type strains of the genus Kibdelosporangium. The chemotaxonomic properties further supported the assignment of strain XMU 506T to the genus Kibdelosporangium: meso-diaminopimelic acid was the diagnostic amino acid in the cell wall peptidoglycan; mycolic acids were not present in the cell wall; the whole-cell hydrolysates contained arabinose, galactose, glucose and ribose. The major menaquinone was MK-9(H4); the phospholipids of the isolate comprised phosphatidylethanolamine, OH-phosphatidylethanolamine, diphosphatidylglycerol and unidentified amino-, glyco- and phospholipids; the major fatty acids of the strain were iso-C16 : 0, C17 : 1 ω6c and iso-C16 : 1 H. The G+C content of genomic DNA was 67.3 mol%. Based on the results of phylogenetic analysis, phenotypic and genotypic characterization, strain XMU 506T represents a novel species in the genus Kibdelosporangium, for which the name Kibdelosporangium lantanae sp. nov. is proposed. The type strain is XMU 506T ( = KCTC 29675T = MCCC 1K00430T).

Tumorigenic effects of endocrine-disrupting chemicals are alleviated by licorice (Glycyrrhiza glabra) root extract through suppression of AhR expression in mammalian cells. Endocrine-disrupting chemicals (EDCs) have been reported to interfere with estrogen signaling. Exposure to these chemicals decreases the immune response and causes a wide range of diseases in animals and humans. Recently, many studies showed that licorice (Glycyrrhiza glabra) root extract (LRE) commonly called "gamcho" in Korea exhibits antioxidative, chemoprotective, and detoxifying properties. This study aimed to investigate the mechanism of action of LRE and to determine if and how LRE can alleviate the toxicity of EDCs. LRE was prepared by vacuum evaporation and freeze-drying after homogenization of licorice root powder that was soaked in 80% ethanol for 72 h. We used 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as a representative EDC, which is known to induce tumors or cancers; MCF-7 breast cancer cells, used as a tumor model, were treated with TCDD and various concentrations of LRE (0, 50, 100, 200, 400 μg/mL) for 24, 48, and 72 h. As a result, TCDD stimulated MCF-7 cell proliferation, but LRE significantly inhibited TCDD-induced MCF-7 cell proliferation in a dose- and time-dependent manner. The expression of TCDD toxicity-related genes, i.e., aryl hydrocarbon receptor (AhR), AhR nuclear translocator, and cytochrome P450 1A1, was also down-regulated by LRE in a dose-dependent manner. Analysis of cell cycle distribution after treatment of MCF-7 cells with TCDD showed that LRE inhibited the proliferation of MCF-7 cells via G2/M phase arrest. Reverse transcription-polymerase chain reaction and Western blot analysis also revealed that LRE dose-dependently increased the expression of the tumor suppressor genes p53 and p27 and down-regulated the expression of cell cycle-related genes. These data suggest that LRE can mitigate the tumorigenic effects of TCDD in breast cancer cells by suppression of AhR expression and cell cycle arrest. Thus, LRE can be used as a potential toxicity-alleviating agent against EDC-mediated diseases.

Reproducibility of allergen, endotoxin and fungi measurements in the indoor environment. Measurements of biocontaminants in settled house dust once a year are commonly used to assess long-term exposure. To examine stability over time and seasonal variation, we measured concentrations of mite and cat allergens, endotoxin and mold spores in living room floor dust in 745 German homes collected twice a year in two different seasons. The study population consisted of adults and children living in five different areas in Germany. All dust samples were collected in a standardized manner from the living room floor and taken during the years 1995 to 1998. The median interval between the two dust samplings was approximately 7 months. Mite and cat allergens were measured in settled house dust by monoclonal antibodies, endotoxin by the limulus amebocyte lysate method, and total spore counts by cultural methods. Crude Pearson's correlation coefficients between log-transformed concentrations in the first and second dust samples ranged between 0.65 and 0.75 for allergens, 0.59 for endotoxin and only 0.06 for total spore counts. The strongest and most consistent seasonal effects were observed for fungi with highest levels in July-September. Cat allergen concentrations were found consistently to be increased in January-March. Mite allergens did not show a strong and consistent seasonal pattern. We conclude that repeated measurements of mite and cat allergens and endotoxin in settled house dust improve the estimate for annual mean concentrations. However, even a single observation of these biocontaminants may be a good proxy for a 1-year exposure since repeated measures were highly correlated. However, repeated measurements of fungi levels were only weakly correlated and thus repeated observations for assessment of annual means of total spore counts are needed.

Blood borne macrophages are essential for the triggering of muscle regeneration following muscle transplant. The transplantation of satellite cells may constitute a strategy for rebuilding muscle fibres in inherited myopathies. However, its development requires a great understanding of the role of environmental signals in the regenerative process. It is therefore essential to identify the key events triggering and controlling this process in vivo. We investigated whether macrophages play a key role in the course of the regenerative process using skeletal muscle transplants from transgenic pHuDes-nls-LacZ mice. Before grafting, transplants were conditioned with macrophage inflammatory protein 1-beta (MIP 1-beta; stimulating the macrophages infiltration or vascular endothelial growth factor (VEGF) stimulating angiogenesis). Treatment of transplants with MIP 1-beta and VEGF both accelerated and augmented monocyte-macrophage infiltration and satellite cell differentiation and/or proliferation, as compared to controls. In addition, VEGF treatment enhanced the number of newly formed myotubes. When a complete depletion of host monocyte-macrophages was experimentally induced, no regeneration occurred in transplants. Our data suggest that the presence of blood borne macrophages is required for triggering the earliest events of skeletal muscle regeneration. The understanding of macrophage behaviour after muscle injury should allow us to develop future strategies of satellite cell transplantation as a treatment for muscular dystrophies.

Immunology Driven by Large-Scale Single-Cell Sequencing. The immune system encompasses a large degree of phenotypic diversity and plasticity in its cell types, and more is to be uncovered. We argue that large, multiomic datasets of single-cell resolution, in conjunction with improved computational methods, will be essential to resolving immune cell identity. Existing datasets, combined with 'big data' methodologies, can serve as a platform to support future studies in immunology. Technical and analytical advances in multiomics and spatial integration can provide a reference for gene regulation and cellular interactions in spatially structured tissue contexts. We posit that these developments may allow guided functional studies of immune cell populations and lay the groundwork for informed cell engineering and precision medicine.

School lunches and lunches brought from home: a comparative analysis. Considerable effort has been put forth to improve the nutritional quality of school meals by the National School Lunch Program (NSLP). However, a large percentage of children do not obtain their meals from school and instead bring lunch from home. Little research has focused on the content of these lunches. The purpose of the current study was to examine differences between school lunch and lunch brought from home. Children in the 2nd grade from seven schools in a large suburban school district were observed on three separate days. A total of 2107 observations were made, with 38.5% of these being lunches brought from home. Chi-squared analyses evaluated differences in the presence of specific food items between school lunch and lunch brought from home. Compared to children with a school lunch, children with a lunch brought from home were significantly less likely to have fruits (75.9% vs. 45.3%), vegetables (29.1% vs. 13.2%), and dairy (70.0% vs. 41.8%) (p < 0.001). Children with a lunch from home were more likely to have snacks high in sugar and/or fat (17.5% vs. 60.0%) and non 100% fruit juice/fruit drink (0.3% vs. 47.2%) (p < 0.001) than children with a school lunch. The NSLP has been widely criticized; however, conducting a comparison in this manner demonstrates advantages to children obtaining school lunches. Although it was beyond the scope of this study to examine diet quality (e.g., actual intake and nutrient/caloric density), these results provide compelling evidence that lunches brought from home should be an area of emphasis for research and intervention.

Temporal patterns of evoked cerebral blood flow during reading. This study describes the dynamics of flow activation by reading and investigates the potential use of repeated flow velocity measurements for the lateralization of speech. Using simultaneous transcranial Doppler recordings from both middle cerebral arteries and averaging techniques in 25 healthy volunteers, we describe the changes in blood flow velocity caused by repetitive reading tasks of variable duration in comparison with a resting state. Reading aloud evoked a characteristic temporal flow pattern in both hemispheres, consisting of three relative maxima in flow velocity during and after activation. Flow velocities lower than baseline were common during longer lasting activation. The amplitudes of two of the observed peaks decreased depending on the duration of the task. Reading silently produced a markedly different temporal pattern of activation than reading aloud. There were individually reproducible significant side to side differences. Right-handed persons (n = 15) almost without exception showed a significantly higher increase in flow velocity on the left hemisphere (e.g., reading silently 8.7% versus 5.3%; P < 0.0001). Three out of ten left-handed individuals, however, exhibited no significant side to side difference or exhibited lateralization to the right during one or more of the tasks. These findings suggest that reading induces task-specific temporal patterns of regional neuronal activity, which show habituation with longer duration of activation. Additionally, the observed side to side differences could be useful to predict language dominance.

Gunshot wounds to the head and neck. The types of injury which occur as a result of the civil disturbances in the north of Ireland are described. Four cases of gunshot wounds to the head and neck are described, each of particular clinical interest. The recent literature on the subject is reviewed and the consensus of opinion appears to be that the safest policy is to explore all cases of penetrating wounds of the neck

Live cell imaging and biophotonic methods reveal two types of mutant huntingtin inclusions. Huntington's disease (HD) is an autosomal dominant, neurodegenerative disorder that can be characterized by the presence of protein inclusions containing mutant huntingtin within a subset of neurons in the brain. Since their discovery, the relevance of inclusions to disease pathology has been controversial. We show using super-resolution fluorescence imaging and Förster resonance energy transfer (FRET) in live cells, that mutant huntingtin fragments can form two morphologically and conformationally distinct inclusion types. Using fluorescence recovery after photobleaching (FRAP), we demonstrate that the two huntingtin inclusion types have unique dynamic properties. The ability to form one or the other type of inclusion can be influenced by the phosphorylation state of serine residues at amino acid positions 13 and 16 within the huntingtin protein. We can define two types of inclusions: fibrillar, which are tightly packed, do not exchange protein with the soluble phase, and result from phospho-modification at serines 13 and 16 of the N17 domain, and globular, which are loosely packed, can readily exchange with the soluble phase, and are not phosphorylated in N17. We hypothesize that the protective effect of N17 phosphorylation or phospho-mimicry seen in animal models, at the level of protein inclusions with elevated huntingtin levels, is to induce a conformation of the huntingtin amino-terminus that causes fragments to form tightly packed inclusions that do not exit the insoluble phase, and hence exert less toxicity. The identification of these sub-types of huntingtin inclusions could allow for drug discovery to promote protective inclusions of mutant huntingtin protein in HD.

Highly selective hydrolytic kinetic resolution of terminal epoxides catalyzed by chiral (salen)Co(III) complexes. Practical synthesis of enantioenriched terminal epoxides and 1,2-diols. The hydrolytic kinetic resolution (HKR) of terminal epoxides catalyzed by chiral (salen)Co(III) complex 1 x OAc affords both recovered unreacted epoxide and 1,2-diol product in highly enantioenriched form. As such, the HKR provides general access to useful, highly enantioenriched chiral building blocks that are otherwise difficult to access, from inexpensive racemic materials. The reaction has several appealing features from a practical standpoint, including the use of H(2)O as a reactant and low loadings (0.2-2.0 mol %) of a recyclable, commercially available catalyst. In addition, the HKR displays extraordinary scope, as a wide assortment of sterically and electronically varied epoxides can be resolved to > or = 99% ee. The corresponding 1,2-diols were produced in good-to-high enantiomeric excess using 0.45 equiv of H(2)O. Useful and general protocols are provided for the isolation of highly enantioenriched epoxides and diols, as well as for catalyst recovery and recycling. Selectivity factors (k(rel)) were determined for the HKR reactions by measuring the product ee at ca. 20% conversion. In nearly all cases, k(rel) values for the HKR exceed 50, and in several cases are well in excess of 200.

Manifest refraction versus autorefraction for patients with subfoveal choroidal neovascularization. To compare the results from manifest refraction using trial lenses and a standard visual acuity protocol to results from autorefraction for obtaining refractive error and best corrected visual acuity in patients enrolled in a randomized clinical trial. During a 4-month period, 29 patients with subfoveal choroidal neovascularization (CNV), who were enrolled in the Submacular Surgery Trials (SSTs) Pilot Study at the Wilmer Ophthalmological Institute, gave verbal consent to participate in this study. Best corrected visual acuity was obtained using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity charts and standardized room lighting after performance of manifest refraction, according to the SST protocol, and autorefraction. Refractive error (spherical equivalent) and visual acuity scores were obtained in both eyes of all patients. On average, manifest refraction gave a spherical equivalent that was 1.04 D more plus than autorefraction (95% limits of agreement = 0.74, 1.34). On average, the visual acuity score was 1.5 letters better after manifest refraction than after autorefraction (95% limits of agreement = 0, 3.0). The comparison of the two methods of refraction was subdivided according to visual acuity level and eye disease (age-related macular degeneration or ocular histoplasmosis syndrome). Despite large differences in spherical equivalent between manifest refraction and autorefraction, the visual acuity scores were close (mean difference, 1.5 letters). Other studies comparing subjective refraction and autorefraction have shown similar results. Autorefraction in patients with subfoveal CNV may be a satisfactory alternative to manifest refraction in clinical trials and field studies in which best corrected visual acuity is of interest.

Effects of age on the glucoregulatory response following acute glucoprivation induced by 2-deoxyglucose (2DG) in the adrenal medulla of Sprague Dawley rats. Impairment in glucose homeostasis is one of the factors that may alter the feeding drive, hunger and satiety signals, which essential to maintain a sufficient level of energy for daily activities especially among the elderly. Adrenal medulla is one of the important organs that involves in glucose homeostasis through secretion of catecholamines. The catecholamines biosynthesis pathway utilizes various enzymes and protein kinases. The aims of this study are to investigate the effects of age on the biosynthetic pathway of catecholamines in adrenal medulla by determining the level of blood glucose and blood catecholamines, the gene and protein expression of biosynthetic catecholamine enzymes (TH, DBH and PNMT) as well as protein kinase substrates that involved in the phosphorylation of TH in 2DG-induced rats. Adrenal medulla from male Sprague Dawley rats at the age of 3-months (n=12) and 24-months (n=12) were further divided into two groups: 1) treatment group with 2DG to create glucoprivation condition and 2) the vehicle group which received normal saline as control. The results showed that the level of glucose, adrenaline and noradrenaline were increased in response to acute glucoprivation conditions in both young and old rats. No age-related differences were found in the basal gene expression of the enzymes that involved in the catecholamines biosynthesis pathway. Interestingly the expressions of TH and DBH protein as well as the level of TH phosphorylation at Ser40, PKA, PKC and ERK1/2 substrates were higher in basal condition of the aged rats. However, contradicted findings were obtained in glucoprivic condition, which the protein expressions of DBH, pERK1/2 and substrates for pPKC were increased in young rats. Only substrate for pCDK was highly expressed in the old rats in the glucoprivic condition, while pPKC and pERK1/2 were decreased significantly. The results demonstrate that adrenal medulla of young and old rats are responsive to glucose deficit and capable to restore the blood glucose level by increasing the levels of blood catecholamines. The present findings also suggest that, at least in rats, aging alters the protein expression of the biosynthetic catecholamine enzymes as well as protein kinase substrates that may attenuate the response to glucoprivation.

Electroretinographic responses that may reflect activity of parvo- and magnocellular post-receptoral visual pathways. The electroretinogram (ERG) is a complex retinal response to visual stimuli that contains receptoral and post-receptoral components. Here, data are presented using stimuli that isolate the responses of L (long wavelength sensitive)- or M (middle wavelength sensitive)-cones or that stimulate the two simultaneously. The data show that at a temporal frequency of 12 Hz, ERG responses are L- to M-cone opponent with little inter-individual variability. Furthermore, the ratio of L- to M-cone-driven response strengths in the ERGs is about unity. These are also properties of the L- and M-cone opponent chromatic channel mediated by parvocellular activity. Similar to the parvocellular-mediated temporal sensitivity, the ERG response is robust to moderate changes in state of cone adaptation. Thus, the 12-Hz ERG shares distinct characteristics with the post-receptoral red-green sensitive parvocellular pathway. At higher temporal frequencies, the responses are not cone opponent, the inter-individual variability is larger, the mean L/M ratio is larger than unity, and the responses change more strongly when the state of cone adaptation is altered. These properties are reminiscent of the magnocellular non-opponent channel. The data suggest that under well-controlled conditions, the ERG can be used to study post-receptoral processes of the visual system.

Determination and application of the permitted daily exposure (PDE) for topical ocular drugs in multipurpose manufacturing facilities. Limits for the carry-over of product residues should be based on toxicological evaluation such as described in the "Guideline on setting health based exposure limits for use in risk identification in the manufacture of different medicinal products in shared facilities". The toxicological evaluation should be performed also for locally administered drugs to ensure patient safety. Currently, there is no guidance on setting PDE for ocular drug substances in particular. The purpose of this investigation was to identify and describe a method for calculating a PDE value for topical ocular drugs (PDEocular). As an alternative method, extrapolation of a PDE for systemically administered drugs to a PDEocular is presented. These methods may be applied in cross-contamination risk assessments for manufacturing of topical ocular drugs. Similarly, the methods apply to systemically administered drugs, if their production precedes manufacturing of a topical ocular drug. We have examined pharmacokinetic (PK) properties of topical ocular drugs and compared them to the PK parameters of systemically administered drugs. Furthermore, we examined possible adverse effects of the carry-over in topical ocular drugs at therapeutic doses.

In vivo and in vitro effects of Sizofiran on the human neutrophils and the serum opsonic activity. In this paper, we examine the effects of SPG, which is a well known BRM, both in vivo and in vitro on the neutrophilic ROS production and the serum opsonic activity by the chemiluminescence technique using luminol as a probe. To investigate the in vivo effects, SPG was administered to 12 healthy male volunteers and two phases of enhancement of the neutrophilic ROS production and the serum opsonic activity was observed. In vitro, the addition of SPG showed a dose-dependent suppression. To investigate the mechanisms in these contradictory effects of SPG, supernatants of a lymphocytes culture medium in the presence of SPG with or without mitogen were added to the neutrophils. The addition of supernatants at a lower concentration of SPG (0.01 mg/ml) with mitogens showed significant preventive effects on the neutrophilic ROS production for the duration of incubation. This suggests that cytokines derived from lymphocytes may contribute to the in vivo effects of SPG. SPG can play an important role in the host's defense against microbe infections by enhancing it's effect on non-specific immunity when administered in vivo.

Mutations in subunits of the Escherichia coli twin-arginine translocase block function via differing effects on translocation activity or tat complex structure. We have used a combination of blue-native (BN) gel electrophoresis and protein purification to analyze the effects of TatA or TatC mutations on the structures of the primary TatABC and multimeric TatA complexes in Escherichia coli. Expression of wild-type TatABC leads to the production of a single major TatABC complex of 370 kDa and a heterogeneous set of TatA complexes of <100 kDa to approximately 500 kDa. Two TatC mutations that block translocation have different effects on complex structures. P48A causes massive defects in TatABC assembly, including a marked separation of the TatBC subunits and the production of TatB and TatC aggregates. In contrast, TatABC complexes from the inactive TatC F94A mutant are structurally intact, suggesting that this mutation affects translocation activity rather than assembly. Neither TatC mutation affects the separate TatA complexes, showing that assembly of the TatA complexes is independent of TatABC assembly or activity. In contrast, three TatA mutations affect both the TatA and TatABC complexes. F39A assembles into smaller, incorrectly organized TatA complexes and the TatABC complexes contain an incorrect TatB:TatC ratio and unusually large amounts of TatA. A triple mutant in the amphipathic region forms slightly larger TatA complexes that are likewise disorganized, and a mutant containing three glycine substitutions in the transmembrane (TM) span assembles as grossly affected TatA complexes that are much larger than wild-type complexes. These mutants lead to a partial failure of TatB to assemble correctly. The data show that the amphipathic and TM regions play critical roles in TatA complex assembly. All of the TatA mutations lead to partial or substantial defects in TatABC complex formation, demonstrating that the properties of TatA can have a marked influence on the TatABC complex.

Clinical significance of childhood communication disorders: perspectives from a longitudinal study. A group of 202 children who were referred for evaluation of communication disorders were also evaluated for psychiatric and learning disorders at two points in time. High rates of both psychiatric and learning disorders were found at initial evaluation, and even higher rates were found at follow-up 3 to 4 years later. Recovery from communication disorder occurred in approximately one fourth of the cases and varied widely depending on the type of disorder involved. Poor psychiatric outcome could be predicted by the presence and severity of initial disorders of language comprehension and expression, and by certain environmental factors (such as psychosocial stress). The high prevalence of linguistic, psychiatric, and development disorders at follow-up for the children in this study suggests the need for close monitoring of children with early communication impairments.

CB1-cannabinoid receptors are involved in the modulation of non-synaptic [3H]serotonin release from the rat hippocampus. In the present study we investigated whether serotonin release in the hippocampus is subject to regulation via cannabinoid receptors. Both rat and mouse hippocampal slices were preincubated with [3H]serotonin ([3H]5-HT) and superfused with medium containing serotonin reuptake inhibitor citalopram hydrobromide (300 nM). The cannabinoid receptor agonist R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl) methanone mesylate (WIN55,212-2, 1 microM) did not affect either the resting or the electrically evoked [3H]5-HT release. In the presence of the ionotropic glutamate receptor antagonists D(-)-2-amino-5-phosphonopentanoic acid (AP-5, 50 microM) and 6-cyano-7-nitroquinoxaline-2,3-dione-disodium (CNQX, 10 microM) the evoked [3H]5-HT release was decreased significantly. Similar findings were obtained when CNQX (10 microM) was applied alone with WIN55,212-2. This effect was abolished by the selective cannabinoid receptor subtype 1 (CB1) antagonists N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716, 1 microM) and 1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-1-piperidinyl-1H-pyrazole-3-carboxamide trifluoroacetate salt (AM251, 1 microM). Similarly to that observed in rats, WIN55,212-2 (1 microM) decreased the evoked [3H]5-HT efflux in wild-type mice (CB1+/+). The inhibitory effect of WIN55,212-2 (1 microM) was completely absent in hippocampal slices derived from mice genetically deficient in CB1 cannabinoid receptors (CB1-/-). Relatively selective degeneration of fine serotonergic axons by the neurotoxin parachloramphetamine (PCA) reduced significantly the tritium uptake and the evoked [3H]5-HT release. In addition, PCA, eliminated the effect of WIN55,212-2 (1 microM) on the stimulation-evoked [3H]5-HT efflux. In contrast to the PCA-treated animals, WIN55,212-2 (1 microM) reduced the [3H]5-HT efflux in the saline-treated group. Our data suggest that a subpopulation of non-synaptic serotonergic afferents express CB1 receptors and activation of these CB1 receptors leads to a decrease in 5-HT release.

β-Thalassemia trait association with autoimmune diseases: β-globin locus proximity to the immunity genes or role of hemorphins? Thalassemia major continues to be a significant health problem for Mediterranean, Afro-Arabic countries, India and South Easth Asia. It was generally assumed that the β-thalassemia heterozygotes do not bear significant medical risks except a mild microcytic anemia. Nonetheless, increasing number of reports associate β-thalassemia trait with autoimmune conditions, nephritis, diabetes, arthritis, fibromyalgia and asthma. Available sparse data indicate reduced incidence of systemic lupus erythematosus (SLE) in β-thalassemia heterozygotes; yet, if two conditions coexist, the SLE manifestations occur much severer. These associations make sense when considering that the hemoglobin β-chain locus at 11p15.5 resides in close proximity to eight genes with profound roles in immune regulation: STIM1, CD151, TC21/RRAS2, SIGIRR/TOLL/IL1R8, pp52/LSP1 (lymphocyte specific protein), TRIM21, toll interacting protein (TOLLIP) and SLEN3. β-Thalassemia trait accompaniment to autoimmune disease may be the result of haplotypal associations between the close proximity genes. An alternative explanation to thalassemia heterozygosity: autoimmune disease association may be the changed concentrations of hemorphins. Hemorphins are endogenous opioid peptides derived via proteolytical cleavage of hemoglobin. They are shown to bind diverse opioid receptors and act anti-inflammatory. Their reduced expression in thalassemia heterozygosity may explain a proinflammatory stage and autoimmunity vulnerability.

[Renoenterocolic fistula]. We present a case of reno-entero-colic fistula which is extremely rare and which, in the face of unspecific clinical pictures requires a detailed examination. Its physiopathology, the surgical problems which it poses and the means of solving these, are explained.

Absence of serum prostate-specific antigen and loss of tissue immunoreactive prostatic markers in advanced prostatic adenocarcinoma after hormonal therapy: a report of two cases. We report two cases of advanced prostatic adenocarcinoma (PA) showing complete loss of three tissue immunoreactive prostatic markers, ie, prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), and Leu-7 (CD57), with absence of elevated serum PSA level, despite tumor progression after hormonal therapy with or without radiotherapy. The pretreatment serum PAP in the first case and serum PAP and PSA in the second case were elevated. In both cases, the prostatic adenocarcinoma in the initial transurethral resection specimens showed positive immunoreactivity with three prostatic markers. After treatment, in both cases, the serum PSA were undetectable, and tumor cell immunostaining for three prostatic markers was negative. In addition, the posttreatment tumors in both cases showed increased number of tumor cells with neuroendocrine differentiation in comparison those in the pretreatment tumors. Although early PA without elevated serum level of PSA is common, advanced PA with absence of elevated serum PSA, associated with presence of tissue immunoreactive prostatic markers are rare. This is the first report of advanced prostatic adenocarcinomas showing loss of tumor cell prostate-specific markers with absence of elevated serum PSA level after hormonal therapy despite tumor progression.

Cystic hygroma of the neck: association with a growing venous aneurysm. Venous anomalies are rarely seen with cystic hygromas. We describe an unusual case of cystic hygroma of the neck associated with a saccular venous aneurysm that was increasing in size. A multi-modality examination of the neck-including CT, Doppler sonography, and MR imaging-revealed multiloculated cystic lesions bilaterally with predominance on the left side. A saccular venous aneurysm was noted within one of the sacs. Comparison with previous CT images showed that the aneurysm enlarged from 0.8 x 0.5 x 1.5 cm to 3.0 x 1.3 x 2.1 cm over 2 years. Identification of these malformations before surgery is critical.

[Applications of mathematical statistics methods on compatibility researches of traditional Chinese medicines formulae]. The compatibility of traditional Chinese medicines (TCMs) formulae containing enormous information, is a complex component system. Applications of mathematical statistics methods on the compatibility researches of traditional Chinese medicines formulae have great significance for promoting the modernization of traditional Chinese medicines and improving clinical efficacies and optimizations of formulae. As a tool for quantitative analysis, data inference and exploring inherent rules of substances, the mathematical statistics method can be used to reveal the working mechanisms of the compatibility of traditional Chinese medicines formulae in qualitatively and quantitatively. By reviewing studies based on the applications of mathematical statistics methods, this paper were summarized from perspective of dosages optimization, efficacies and changes of chemical components as well as the rules of incompatibility and contraindication of formulae, will provide the references for further studying and revealing the working mechanisms and the connotations of traditional Chinese medicines.

Long-term follow-up of occlusion of the central retinal vein in young adults. We did a long-term follow-up study of 42 patients aged 40 years and younger who had occlusion of the central retinal vein in order to learn its course and determine the frequency of related systemic disorders. Two groups of venous occlusion (complete and incomplete) were delineated by initial ocular findings. Final visual prognosis could not be predicted by the severity of the venous occlusion at the time of diagnosis. The presence of anomalous disk vessels closely correlated with a favorable prognosis in patients who had complete occlusion of the central retinal vein. None of the patients with incomplete central vein occlusion developed neovascular glucoma; three (14%) of the 21 patients with complete venous occlusion developed neovascular glucoma, which resulted in enucleation. Significant associated systemic maladies included cardiovascular disease and diabetes mellitus. An apparent correlation exists between occlusion of the central retinal vein and early death.

Effects of halogenated hydrocarbon anesthetics on responses to ligation of a coronary artery in chronically prepared rats. Responses to ligation of the left anterior descending coronary artery (blood pressure, heart rate, ECG, arrhythmias, myocardial tissue loss, and mortality) were investigated in chronically prepared rats anesthetized with one of various halogenated hydrocarbon anesthetics. Halothane (inhaled concentrations of 0, 0.25, 0.5, 1.0, and 2.0%) reduced arrhythmias, mortality, and "S-T" segment changes in the ECG in a dose-related manner. The most effective antiarrhythmic concentrations were 0.5 and 1.0%. Other halogenated hydrocarbon anesthetics (chloroform, enflurane, isoflurane, methoxyflurane, and trichlorethylene) were investigated at minimal anesthetic concentrations. Of these, only chloroform and enflurane reduced arrhythmias. However, both increased mortality as a result of nonarrhythmic causes. At one-half anesthetic concentrations, chloroform (0.25%) and enflurane (0.75%) were not antiarrhythmic and mortality resulting from nonarrhythmic causes was not increased. In the chronically prepared rat, halothane at anesthetic and subanesthetic concentrations has antiarrhythmic actions against ligation-induced arrhythmias, reducing mortality. Of the other halogenated hydrocarbons tested, only enflurane and chloroform had antiarrhythmic actions, however, mortality was high with both agents because of accompanying cardiovascular depression.

Y-Stent-Assisted Coiling With Low-Profile Neuroform Atlas Stents for Endovascular Treatment of Wide-Necked Complex Intracranial Bifurcation Aneurysms. Y-stent-assisted coiling is one of the eligible techniques for the treatment of complex bifurcation aneurysms. In majority of previous literature, Y-stenting has been performed using stents that could be delivered through large profile microcatheters that are often difficult to manipulate during navigation through sharply angled side branches. Attempts to navigate with these large profile catheters might cause serious complications during Y-stenting procedure. To investigate the safety, feasibility, and efficacy of Y-stent-assisted coiling procedure with Neuroform Atlas stents for the treatment of complex bifurcation aneurysms; Neuroform Atlas is a recently introduced open-cell stent that can be delivered though low-profile microcatheters. We identified the patients with intracranial bifurcation aneurysms treated by Y-stent-assisted coiling procedure with Neuroform Atlas stents. We assessed the immediate postoperative and follow-up clinical and angiographic outcomes. We also investigated the periprocedural and delayed complications. A total of 30 aneurysms in 30 patients were included in the study. Y-stenting was successfully performed without any technical complications in all cases (100%). Immediate postprocedural angiography revealed total aneurysm occlusion in 83.3% of patients. The mean angiographic follow-up time was 11.8 mo. The last follow-ups showed complete occlusion in 93.3% of patients. There was no mortality in this study. A procedure-related complication developed in 6.7% and resulted in permanent morbidity in 3.3% of patients. Neuroform Atlas stent combines the advantages of low-profile deployment microcatheters with an open-cell structure to achieve a successful Y-stenting procedure. Y-stent-assisted coiling with Neuroform Atlas stents provides a safe and effective endovascular treatment for wide-necked complex bifurcation aneurysms.

Metyrapone pretreatment prevents the behavioral and neurochemical sequelae induced by stress. In the present study, we examined the effect of metyrapone, an inhibitor of corticosterone (CS) synthesis, on the behavioral and neurochemical sequelae induced by a brief restraint session. A 15-min stress period induced an anxiogenic-like behavior on the elevated plus-maze (EPM), which was reversed with metyrapone (75 mg/kg i.p.) injected 3 h prior to the stress event. It was further demonstrated that metyrapone pretreatment normalized the decrease in maximal chloride uptake following GABA stimulation observed in brain cortex tissue obtained from animals exposed to both restraint and the EPM. In addition, plasma CS levels were assessed both after restraint and following EPM exposure. Furthermore, the administration of both CS (2.5 mg/kg s.c. at a dose that mimics CS levels induced by restraint) or dexamethasone (DEXA, 1.25 microg/kg s.c) resulted in an anxiogenic response in the EPM comparable to that induced by restraint. Taken together, all these evidence suggest that CS released in response to stress seems to be associated with functional changes at the GABAergic supramolecular complex which could underlie the enhanced anxiety observed following the exposure to an aversive experience.

Endovascular treatment of popliteal artery aneurysms: preliminary results. Popliteal artery aneurysms (PAAs) are a rare condition with an incidence <0.1%. The objective of this study was to evaluate the effectiveness of endovascular treatment of PAA with a covered stent-graft. Between January 2009 and July 2010, ten patients (nine men and one woman, mean age 69 ± 12 years) with PAA were treated by endovascular placement of a heparin-coated stent-graft. All procedures were evaluated in terms of technical success, patency at 1, 6 and 12 months as assessed by colour Doppler ultrasound, complications, procedure duration and length of postoperative hospital stay. We obtained 100% technical success, with no peri- or postprocedural complications. Average duration of the procedure was 40 min, and mean hospital stay was 3 days. Primary and secondary patency rates at 1, 6 and 12 months were 100% and 100%, 90% and 100%, and 90% and 100%, respectively. Only one case of endoleak occurred. In keeping with the literature, our study demonstrates the effectiveness of endovascular repair of PAA, with short- and mid-term patency rates comparable to those of open surgery. Larger series and longer follow-up periods are needed to confirm these preliminary results.

Western diet in ApoE-LDLR double-deficient mouse model of atherosclerosis leads to hepatic steatosis, fibrosis, and tumorigenesis. Nonalcoholic fatty liver disease has been linked to cardiovascular diseases and atherosclerosis. The aim of the current study was to characterize the hepatic pathology leading to fibrosis and tumors in a murine model of atherosclerosis. Male apolipoprotein E/low-density lipoprotein receptor double-knockout mice (AL) mice were fed with a high fat and high cholesterol western diet for 35 weeks (AL mice on WD). Protein and mRNA analysis as well as micro-computed tomography (micro-CT) were performed to assess oxidative stress, liver damage, inflammation, fibrosis, signaling pathways, vascularization, and tumorigenesis. Controls were chosen to distinguish between genetically and dietary effects in steatohepatitis and associated tumorigenesis. Hepatic inflammation and dyslipidemia were increased in AL mice on WD compared with wild-type mice on WD. Uniquely, AL mice on WD showed a spontaneous development of tumors (30% of cases) and thickening of intrahepatic vessel walls. Functionally relevant underlying signaling pathways such as NF-κB, Stat3, JNK, and AKT were differentially regulated between AL and wild-type mice on WD. Micro-CT was capable of visualizing and quantitatively distinguishing tumor neovascularization from vascularization in non-neoplastic liver tissue. AL mice on WD diet represent a novel model combining atherosclerosis and nonalcoholic fatty liver disease. Signaling pathways of liver cell damage and compensatory liver regeneration in combination with enhanced inflammation appear to be crucial for the spontaneous development of tumors in AL mice on WD. Micro-CT represents a new and powerful technique for the ultrastructural and three-dimensional assessment of the vascular architecture of liver tumors.

[A meta-analysis of surgery treatment of chronic pancreatitis with an inflammatory mass in the head of pancreas: duodenum-preserving pancreatic head resection versus pancreatoduodenectomy]. To compare the safety and effectiveness of DPPHR with PPPD/PD for treating chronic pancreatitis with an inflammatory mass in the head of pancreas. The relative data bases such as Medline, EMBase, Biosis, COCHRANE Library, Science Citation Index, SinoMed, Chinese Journal Full-text Database, Wangfang, CNKI were searched systematically, researchers selected randomized controlled trials (RCT) and prospective clinical controlled trials (CCT) . The assessment of the bias risk of the included trials was according to the assessing tools suggested by Cochrane Handbook 5.1. The Review Manage 5.2 was used to perform the statistical analysis. In total, 5 RCTs and 2 CCTs were included, 381 patients involved. Comparing with PPPD/PD procedure, DPPHR has no significant difference in terms of the mortality of perioperative period (RD = 0.01, P = 0.51), the incidence of bleeding (RD = -0.01, P = 0.72), pancreatic fistula(RD = -0.01, P = 0.59) and delayed gastric emptying (RD = -0.15, P = 0.10), the ration of complete pain relief after operation (RR = 1.06, P = 0.32) and the score of global quality of life (WMD = 10.31, P = 0.19).While DPPHR had significant superiorities in terms of the total morbidity of perioperative period (RR = 0.60, P = 0.008), the duration of the operations(WMD = -71.60, P = 0.03), the postoperative hospitalization duration(WMD = -3.95, P < 0.01), weight gain(WMD = 3.68, P < 0.01), occupational rehabilitation after the operations (RR = 1.38, P = 0.008). In terms of reducing the morbidity of perioperative period, shortening the duration of the operations and the postoperative hospitalization duration, weight gain, occupational rehabilitation after the operations, the DPPHR is more favorable for improving patients' life qualities comparing with PPPD/PD.

The Genetics of Warfarin Dose-Response Variability in Africans: An Expert Perspective on Past, Present, and Future. Coumarins such as warfarin are prescribed for prevention and treatment of thromboembolic disorders. Warfarin remains the most widely prescribed and an anticoagulant of choice in Africa. Warfarin use is, however, limited by interindividual variability in pharmacokinetics and a narrow therapeutic index. The difference in patients' pharmacodynamic responses to warfarin has been attributed to genetic variation in warfarin metabolism and molecular targets (e.g., CYP2C9 and VKORC1) and host-environment interactions. This expert review offers a synthesis of human genetics studies in Africans with respect to pharmacogenetics-informed warfarin dosing. We identify areas that need future research attention or could benefit from harnessing existing pharmacogenetics knowledge toward rational and optimal therapeutics with warfarin in African patients. A literature search was conducted until January 2019. A total of 343 articles were retrieved from nine African countries: Botswana, Ethiopia, Egypt, Ghana, Kenya, South Africa, Sudan, Tanzania, and Mozambique. We found 19 studies on genetics of warfarin treatment specifically among Africans. Genes examined included CYP2C9, VKORC1, CYP4F2, APOE, CALU, GGCX, and EPHX1. CYP2C9*2 and *3 alleles were highly frequent among Egyptians, while rare in other African populations. CYP2C9*5, *8, *9, and *11, and VKORC1 Asp36Tyr genetic variants explained warfarin variability in Africans better, compared to CYP2C9*2 and *3. In Africa, there is limited pharmacogenetics data on warfarin. Therefore, future research and funding commitments should be prioritized to ensure safe and effective use of warfarin in Africa. Lessons learned in Africa from the science of pharmacogenetics would inform rational therapeutics in hematology, cardiology, and surgical specialties worldwide.

The effects of prenatal exposure to low-level cadmium, lead and selenium on birth outcomes. To evaluate the current maternal and fetal exposure to cadmium (Cd), lead (Pb) and selenium (Se), and their potential effect on newborn birth outcomes, a cross-sectional study involving an assessment of the levels of these three metals in maternal blood, urine and umbilical cord blood was conducted in 209 pregnant women living in Eastern China. The maternal blood, urine and cord blood samples were collected and measured with inductively coupled plasma mass spectrometry (ICP-MS). The maternal blood concentrations of Cd, Pb and Se (the geometric means (GMs) were 0.48, 39.50 and 143.53 μg L(-1)) were significantly higher than and correlated with those in the cord blood (GM: 0.09, 31.62 and 124.61 μg L(-1)). In the urine samples, the GMs for Cd, Pb and Se were 0.13, 0.48, and 4.78 μg L(-1), respectively. Passive smoking was found to positively correlate with urine Cd (r=0.16) and negatively correlate with urine Se (r=-0.29). The maternal blood Se level was negatively associated with the cord Cd levels (r=-0.41). The blood Cd concentration in the mother could significantly affect the newborn birth weight (r=-0.22), but it was not correlated with birth height. We identified cord Se as a new factor which significantly correlated with birth weight. In conclusion, maternal Cd, Pb, Se exposure correlated with their umbilical cord concentration, and maternal Cd exposure might affect the newborn birth weight. Increasing the Se intake might reduce the cord blood Cd concentration and promote the fetal growth.

Is the treatment of the small saphenous veins with foam sclerotherapy at risk of deep vein thrombosis? To assess the deep vein thrombosis risk of the treatment of the small saphenous veins depending on the anatomical pattern of the veins. A multicenter, prospective and controlled study was carried out in which small saphenous vein trunks were treated with ultrasound-guided foam sclerotherapy. The anatomical pattern (saphenopopliteal junction, perforators) was assessed by Duplex ultrasound before the treatment. All patients were systematically checked by Duplex ultrasound 8 to 30 days after the procedure to identify a potential deep vein thrombosis. Three hundred and thirty-one small saphenous veins were treated in 22 phlebology clinics. No proximal deep vein thrombosis occurred. Two (0.6%) medial gastrocnemius veins thrombosis occurred in symptomatic patients. Five medial gastrocnemius veins thrombosis and four cases of extension of the small saphenous vein sclerosis into the popliteal vein, which all occurred when the small saphenous vein connected directly into the popliteal vein, were identified by systematic Duplex ultrasound examination in asymptomatic patients. Medial gastrocnemius veins thrombosis were more frequent (p = 0.02) in patients with medial gastrocnemius veins perforator. A common outlet or channel between the small saphenous vein and the medial gastrocnemius veins did not increase the risk of deep vein thrombosis. Deep vein thrombosis after foam sclerotherapy of the small saphenous vein are very rare. Only 0.6% medial gastrocnemius veins thrombosis occurred in symptomatic patients. However, the anatomical pattern of the small saphenous vein should be taken into account and patients with medial gastrocnemius veins perforators and the small saphenous vein connected directly into the popliteal vein should be checked by Duplex ultrasound one or two weeks after the procedure. Recommendations based on our everyday practice and the findings of this study are suggested to prevent and treat deep vein thrombosis.

Community-based adolescent health services in Israel: from theory to practice. Despite their engagement in health-risk behaviors and their health-related concerns, adolescents have the lowest rate of health service utilization of any age group. Time constraints during routine medical encounters generally leave little opportunity for professional screening for health-risk behaviors or for discussing psychosocial problems. In addition, providers express low levels of perceived competency in areas such as sexuality, eating disorders or drug abuse. To address these needs, a walk-in Adolescent Health Service was established by the Sheba Medical Center to provide diagnosis and short-term treatment for individual adolescents, as well as counseling and support for local care providers. A three-way model of cooperation and partnership was developed and implemented. A professional and financial partnership with local authorities were established to help define the particular needs of the community's youth and to improve the ability to reach youth with special health needs. The partnership along with the main medical provider (Kupat Holim Clalit) helped define local health needs, served as a referral source of patients with unmet health needs, and improved the continuity of care. The regional medical center (Sheba Medical Center) provided supervision and consultation for the medical staff of the service, as well as a referral center for patients. It was emphasized that the service staff was intended as a professional source for the primary physician and should not be considered a rival. The core staff included a specialist in adolescent medicine, gynecologist, mental health specialist and social worker. A structured intake procedure was developed for assessing health concerns and problems of adolescents in the context of a community clinic. Findings from the first years of services showed that the first 547 female adolescents demonstrated that a majority of adolescents presented with primary complaints of a somatic nature, while one third were diagnosed with psychosocial problems and one-fifth with a sexuality-related problem. A considerable percentage of those diagnosed with psychosocial or sexuality-related problems had not stated these issues as their "reason for encounter". This additional increment probably represents the contribution of the Health Concern Checklist (HCC), in which the adolescent was asked to mark each item for which she had concerns or would like to receive further information. The HCC can help primary care physicians as well as adolescent medical specialists approach the teenage patient and initiate productive communication. A practical approach to confidential health care for adolescents: The issue of confidentiality has not been sufficiently clarified by Israeli law or by the medical community. The need for confidentiality was strongly felt in the adolescent health service. A policy which provides all adolescents with the opportunity to meet with a physician and receive health guidance or advice at least once, even without parental knowledge or consent, was formulated and implemented. If parental consent was not feasible, the minor was allowed to give informed consent for medical and psychosocial care for himself/herself, with certain limitations.

Intrauterine levonorgestrel delivered by a frameless system, combined with systemic estrogen: acceptability and endometrial safety after 3 years of use in peri- and postmenopausal women. To evaluate the acceptability and endometrial safety of a novel intrauterine drug delivery system, FibroPlant-levonorgestrel (LNG), combined with estrogen therapy (ET) in 150 peri- and postmenopausal women, followed-up for at least 3 years. This was a prospective, non-comparative study in peri- and postmenopausal women. In the majority of women, treatment with the FibroPlant-LNG intrauterine system (IUS), combined with ET, was initiated during the perimenopausal transitional phase to establish a smooth transition to menopause and suppress the endometrium to prevent endometrial proliferation and bleeding. A 3.5-cm long coaxial fibrous delivery system, delivering approximately 14 microg LNG/day, was used. The calculated duration of release of the system is at least 3 years. The majority of women received percutaneous 17beta-estradiol (Oestrogel), 1.5 mg daily on a continuous basis, which provides sufficient blood levels of estrogen in most women to suppress climacteric symptoms and protect against bone loss. To measure acceptability, women were asked, after they had the IUS in place for a minimum of 3 years, if they would like to continue the combined regimen and if they would accept renewal of the IUS. Endometrial safety was evaluated by transvaginal ultrasound examination and endometrial biopsy in a subset of 101 women prior to replacement of the IUS. Ninety-four insertions were done in perimenopausal and 56 in postmenopausal women aged between 33 and 78 years. Of the total group of 150 women, 132 women (88.0%) accepted replacement of the IUS and ten are waiting for replacement. This group includes nine women who will receive a second replacement. The number of women continuing the method is 142 (94.6%). Histological examinations conducted on endometrial biopsies from 101 postmenopausal women prior to replacement, after an average period of use of the regimen of 40 months (range 25-50 months), showed predominantly inactive endometrium characterized by pseudodecidual reaction of the endometrial stroma with endometrial atrophia, which is in keeping with the effects seen with a progestogenic compound. There were no specimens showing signs of proliferation. Results suggest that the frameless FibroPlant-LNG IUS is safe, well tolerated, well accepted and effective in suppressing the endometrium during ET. Intrauterine progestogen administration in postmenopausal women can be regarded as fundamentally advantageous compared with systemically applied progestogens, which may have potentially inherent ill side-effects, especially on the breast and cardiovascular system, as reported in the recent literature.

Isotachophoresis for the determination of oxalate in unprocessed urine. The principle of isotachophoresis has been used to develop a simple, specific and sensitive analytical procedure for the determination of oxalate in unprocessed urine. Analytical conditions were optimized. The accuracy and precision of the method were estimated. The specificity was checked with oxalate decarboxylase. Separation of oxalate from a number of organic acids was achieved. The influence of factors such as storage, calcium concentration, pH or ionic strength was examined. The 24-h urine excretion rates for healthy children, healthy adults and for patients with idiopathic stone formation were established. Lower absolute excretion rates were found in children and females. Urinary oxalate/creatinine ratios were higher in children than in adults. The mean oxalate excretion in 24-h urines of adult healthy individuals was 413 +/- 150 mumol per 24 h per 1.73 m2 (range 195-732). The mean oxalate/creatinine ratio was 0.033 +/- 0.011 (range 0.018-0.065).

Norin-10-based semidwarfism. Many short-strawed wheats, including the Norin-10-based semidwarfs now grown in many countries, are characterized by their relative "insensitivity" to gibberellic acid. The nature of this insensitivity, its genetic control, and the relationships between the Gai genes and the Rht genes, which control height reductiion in Norin-10 and Tom Thumb wheats, are described. The role and potential of these genes in agriculture and their relationship to other genes affecting yield, height, and other agronomic features are considered.

Detecting esophageal disease with second-generation capsule endoscopy: initial evaluation of the PillCam ESO 2. Esophageal capsule endoscopy (ECE) provides an alternative, minimally invasive modality for evaluating the esophagus. This study evaluates the performance and test characteristics of a second-generation esophageal capsule endoscope, the PillCam ESO 2. Adults with known or suspected esophageal disease were included. Using the simplified ingestion procedure, each patient underwent capsule endoscopy with the PillCam ESO 2. Following ECE, esophagogastroduodenoscopy (EGD) was performed on the same day by an investigator who was blinded to the results of the ECE. In random order, capsule endoscopy videos were read and interpreted by the study investigator blinded to EGD results. 28 patients (19 men, 9 women; mean age 53.3 years) were included. In 82 % of the patients, at least 75 % of the Z line was visualized by the PillCam ESO 2. A per-lesion analysis demonstrated that the PillCam ESO 2 had definitive results in 30/43 lesions (69.8 %) and EGD in 29/43 (67.4 %), P value = 0.41. Compared with EGD for detecting suspected Barrett's esophagus and esophagitis, the PillCam ESO 2 had a sensitivity of 100 % and a specificity of 74 %, and a sensitivity of 80 % and a specificity of 87 %, respectively. The PillCam ESO 2 demonstrated 86 % agreement with EGD in describing the Z line (kappa statistic 0.68). The modified ingestion protocol provided excellent cleansing, with bubbles/saliva having no or only a minor effect on Z line images in 86 % of cases. The PillCam ESO 2 demonstrated excellent visualization of the Z line. Compared with standard EGD, the PillCam ESO 2 had good test characteristics with high rates of detection of suspected Barrett's esophagus and esophagitis. This study provides indirect validation of the simplified ingestion procedure. The PillCam ESO 2 acquires high quality esophageal images, performs safely, and should be able to replace the current PillCam ESO.

Variations in the frequencies of torque teno virus subpopulations during HAART treatment in HIV-1-coinfected patients. Sera from 15 patients coinfected with TTV and HIV-1, collected before and at two times after introduction of highly active anti-retroviral therapy (HAART), were tested for TTV load and the presence of the five highly divergent TTV phylogenetic groups. Seven patients showed a 1-5 log TTV load decrease during HAART, while the others did not show significant variations. A decrease in the number of coinfecting TTV genogroups was detected in 12 of 15 patients, with the mean number of TTV genogroups/patient decreasing from 2.33 before HAART to 1.47 at the last collect. All five genogroups were less frequently found after introduction of HAART. Three hundred sixty-seven TTV clones from four different genogroups, derived from two patients, were sequenced. Noticeable fluctuations in TTV subpopulation frequencies were observed in both patients analyzed. In conclusion, HAART tends to reduce the number of TTV genotypes/genogroups and may affect the balance between different TTV isolates coinfecting single individuals.

The cerebellum and neuropsychological functioning: a critical review. The cerebellum, while once considered a brain region principally involved in motor control and coordination, is increasingly becoming associated with a range of neuropsychological and neuropsychiatric presentations. This paper reviews the dominant neuropsychological domains and neuropsychiatric conditions for which cerebellar involvement has been demonstrated, including visuospatial functioning, learning and memory, language, executive functioning, attention-deficit/hyperactivity disorder, autism spectrum disorders, and schizophrenia. The paper concludes with a discussion of a potential neuropsychological localization model within the cerebellum and a discussion of prognosis and rates of recovery that can be expected, following localized cerebellar lesions.

Posterior atlantoaxial fusion. A new internal fixation device. Biomechanical and clinical testing of an atlantoaxial posterior fixation device. The authors tested an internal fixation device to maintain the atlas and axis in an anatomic relationship while fusion occurs. The device should also facilitate intraoperative reduction of any residual anterior atlantoaxial subluxation. The device should allow the use of cancellous rather than cortical bone graft. Previous techniques of atlantoaxial fusion were not universally successful, and the quality of reduction was assessed infrequently. Biomechanical testing of the fixator and clinical use in two "problem" patients requiring atlantoaxial fusion. Biomechanical testing indicated the device should be successful. Clinical testing was successful. The new fixator facilitates posterior atlantoaxial fusion in an anatomical position.

[Carcinogenesis in familial polyposis coli]. The inherited cancer disease familial polyposis coli (FPC) provides an excellent model not only for studying tumor progression in colorectal cancer but also for elucidating molecular mechanism of carcinogenesis in general. This paper reviews recent remarkable progress in the molecular mechanism of tumorigenesis in FPC. Included in this review is information on the localization of the FPC major gene and several types of genetic alterations during the development of tumors. One of these genetic alterations is activation of oncogenes such as mutated ras genes and another is inactivation of tumor suppression genes such as loss of heterozygosity. The mutated FPC gene on chromosome 5 q would be expected to be an early event to initiate the requisite hyperproliferation for adenoma formation. Adenomas will have undergone several gene or chromosome mutations before reaching the fully malignant state.

Viability of D283 medulloblastoma cells treated with a histone deacetylase inhibitor combined with bombesin receptor antagonists. Medulloblastoma (MB) comprises four distinct molecular subgroups, and survival remains particularly poor in patients with Group 3 tumors. Mutations and copy number variations result in altered epigenetic regulation of gene expression in Group 3 MB. Histone deacetylase inhibitors (HDACi) reduce proliferation, promote cell death and neuronal differentiation, and increase sensitivity to radiation and chemotherapy in experimental MB. Bombesin receptor antagonists potentiate the antiproliferative effects of HDACi in lung cancer cells and show promise as experimental therapies for several human cancers. Here, we examined the viability of D283 cells, which belong to Group 3 MB, treated with an HDACi alone or combined with bombesin receptor antagonists. D283 MB cells were treated with different doses of the HDACi sodium butyrate (NaB), the neuromedin B receptor (NMBR) antagonist BIM-23127, the gastrin releasing peptide receptor (GRPR) antagonist RC-3095, or combinations of NaB with each receptor antagonist. Cell viability was examined by cell counting. NaB alone or combined with receptor antagonists reduced cell viability at all doses tested. BIM-23127 alone did not affect cell viability, whereas RC-3095 at an intermediate dose significantly increased cell number. Although HDACi are promising agents to inhibit MB growth, the present results provide preliminary evidence that combining HDACi with bombesin receptor antagonists is not an effective strategy to improve the effects of HDACi against MB cells.

Application of the Rietveld method to assess chromium(VI) speciation in chromite ore processing residue. The Rietveld method allows the quantification of crystalline phases and amorphous material identified by X-ray powder diffraction (XRPD) and other diffraction methods. The method assists in determining the speciation of contaminants in solid matrices both qualitatively and quantitatively in a statistically defensible approach, as it does not focus on a microscale. Rietveld was applied to chromite ore processing residue (COPR), a cementitious waste containing hexavalent chromium. Calcium aluminum chromium oxide hydrates (CACs) were the crystalline phases identified by XRPD that bind Cr(6+) in COPR according to their chemical formula. Rietveld quantification, combined with mass balances on Cr(6+), showed that CACs may bind Cr(6+) in variable percentages, ranging from 25% to 85%. Analysis of duplicate samples showed that material variability is the predominant factor of uncertainty in evaluating the role of CACs in Cr(6+) speciation, provided that a consistent quantification strategy is pursued. The choice of strategy was performed on the basis of the pertinent literature, preliminary analyses of the equipment and the software settings, and mass balances. The correlation between the average CAC-bound Cr(6+) concentration and the total Cr(6+) for five samples (R(2)=0.94), extracted from different zones and soil borings, suggests that CACs are a primary sink for Cr(6+) in COPR.

Increased (18)F-deoxyglucose uptake in the lung during the first weeks of radiotherapy is correlated with subsequent Radiation-Induced Lung Toxicity (RILT): a prospective pilot study. As Radiation-Induced Lung Toxicity (RILT) is dose-limiting for radiotherapy (RT) of lung cancer and current parameters are only moderately associated with RILT, we sought for novel parameters associated with RILT. In this prospective study, FDG-PET-CT scans were taken on days 0, 7 and 14 after initiation of high-dose RT in 18 patients with stage III non-small cell lung cancer. The maximal Standardized Uptake Value (SUV(max)) in the lung outside of the GTV was used as a measure of FDG uptake. At the same time-points, the serum IL-6 concentrations were measured. RILT was defined as dyspnea score 2 (CTCAE3.0). Six of 18 patients developed RILT. Before RT, SUV(max) in the lung was not significantly different between patients who developed RILT and those who did not develop RILT. Patients who developed RILT post-radiation had a significant increased SUV on days 7 and 14 during RT, whereas the group that did not experience RILT showed no significant SUV changes. The SUV(max) of the lungs increased significantly more in the group that later developed RILT compared to those who did not develop RILT. Neither the IL-6 concentration nor the mean lung dose was associated with RILT. The increase in FDG uptake in the normal lung early during RT was highly associated with the subsequent development of clinical RILT. This may help to identify patients at high risk for RILT at a time when adjustments of the treatment or strategies to prevent RILT are still possible.

Complexin II is essential for normal neurological function in mice. Complexins (CPLXs) are modulators of synaptic vesicle release. At 1 year of age, CPLXII knockout (KO) mice appear normal. However, behavioral testing reveals underlying deficits of motor and cognitive function in these mice. We found motor deficits on the rotarod, and learning deficits in the Morris water maze (both acquisition and reversal) and the two-choice swim tank (reversal). The reversal learning deficits are particularly noticeable, being present from the earliest time of testing, when most other behaviors are normal. CPLXII KO mice also fail to develop adult patterns of exploratory behavior in the open field and show deficits in interactive grooming behaviors. The behavioral deficits worsen with age. For example, while rotarod performance is normal until 10 weeks, it is impaired from 24 weeks onwards. Similarly, deficits in spatial learning in the Morris water maze are mild at 8 weeks, but pronounced by 1 year of age. The deficits seen in CPLXII KO mice are not due to physical weakness, since their ability to run, swim and grip is unimpaired. Rather, the mice appear to have deficits of higher function. The deficits seen in CPLXII KO mice are strikingly similar to those seen in the R6/2 model of Huntington's disease (HD) where a progressive depletion of CPLXII is seen. This suggests that depletion of CPLXII contributes to cognitive abnormalities in R6/2 mice. Given that decreased expression of CPLXII is seen in HD and schizophrenic patients, a role for CPLXII depletion should be considered in other diseases where motor, cognitive and psychiatric symptoms co-exist.

FGF1-mediated cardiomyocyte cell cycle reentry depends on the interaction of FGFR-1 and Fn14. Fibroblast growth factors (FGFs) signal through FGF receptors (FGFRs) mediating a broad range of cellular functions during embryonic development, as well as disease and regeneration during adulthood. Thus, it is important to understand the underlying molecular mechanisms that modulate this system. Here, we show that FGFR-1 can interact with the TNF receptor superfamily member fibroblast growth factor-inducible molecule 14 (Fn14) resulting in cardiomyocyte cell cycle reentry. FGF1-induced cell cycle reentry in neonatal cardiomyocytes could be blocked by Fn14 inhibition, while TWEAK-induced cell cycle activation was inhibited by blocking FGFR-1 signaling. In addition, costimulation experiments revealed a synergistic effect of FGF1 and TWEAK in regard to cardiomyocyte cell cycle induction via PI3K/Akt signaling. Overexpression of Fn14 with either FGFR-1 long [FGFR-1(L)] or FGFR-1 short [FGFR-1(S)] isoforms resulted after FGF1/TWEAK stimulation in cell cycle reentry of >40% adult cardiomyocytes. Finally, coimmunoprecipitation and proximity ligation assays indicated that endogenous FGFR-1 and Fn14 interact with each other in cardiomyocytes. This interaction was strongly enhanced in the presence of their corresponding ligands, FGF1 and TWEAK. Taken together, our data suggest that FGFR-1/Fn14 interaction may represent a novel endogenous mechanism to modulate the action of these receptors and their ligands and to control cardiomyocyte cell cycle reentry.

In vivo metabolism of apolipoprotein E within the HDL subpopulations LpE, LpE:A-I, LpE:A-II and LpE:A-I:A-II. High-density lipoproteins can be separated into distinct particles based on their apolipoprotein content. In the present study, the in vivo metabolism of apoE within the apoE-containing HDL particles LpE, LpE:A-I, LpE:A-II and LpE:A-I:A-II was assessed in control subjects and in patients with abetalipoproteinemia (ABL), in whom HDL are the sole plasma lipoproteins. The metabolism of apoE within these HDL subspecies was investigated in three separate studies which differed by donor or recipient status: (1) particles purified from normolipidemic plasma and reassociated with 125I or 131I-labeled apoE injected into normolipidemic subjects (study 1); (2) particles purified from ABL plasma injected into normolipidemic subjects (study 2); and (3) particles purified from ABL plasma injected into ABL subjects (study 3). The plasma residence times (RT, hours) in study 1 were 14.3+/-2.9, 11.3+/-3.4, and 9.1+/-1.2 for apoE within LpE:A-I:A-II, LpE:A-II and LpE:A-I, respectively, while those in study 2 were 10.1+/-2.2, 9.7+/-2.4, 7.9+/-1.0 and 7.3+/-0.8 for apoE within LpE:A-I:A-II, LpE:A-II, LpE:A-I and LpE, respectively. In study 3, RTs for apoE within LpE:A-I:A-II and LpE were 8.7+/-0.9 and 6.8+/-0.9, respectively. In comparison, RT for apoA-I on LpA-I:A-II has been reported to be 124.1+/-5.5 h and that for apoA-I on LpA-I 105.8+/-6.2 h. Thus, apoE within the different apoE-containing HDL particles was metabolized rapidly and at a similar rate in control and ABL subjects. The plasma RT of apoE was longest when injected on LpE:A-I:A-II particles and shortest when injected on LpE. In summary, our data show that: (1) the plasma RT of apoE within HDL is approximately ten times shorter than that of apoA-I within HDL, and (2) apoE within HDL is metabolized at a slower rate when apoproteins A-I and A-II are present (LpE:A-I:A-II RT>LpE:A-II>LpE:A-I>LpE). These differences were related to the lipid and apolipoprotein composition of the HDL subspecies, and, in control subjects, to the transfer of apoE from HDL subspecies to apoB-containing lipoproteins as well.

Sixth nerve palsy as a presenting sign of intracranial plasmacytoma and multiple myeloma. Multiple myeloma and plasmacytoma are rare causes of mass lesions at the skull base and cavernous sinus. Sixth nerve palsy, in isolation or in combination with other cranial neuropathies, may occur rarely as the initial presenting feature of multiple myeloma. We report the neuro-ophthalmologic, radiologic, and pathologic findings for two patients who developed sixth nerve palsies as an initial manifestation of intracranial plasmacytoma and multiple myeloma. One patient presented with an isolated sixth nerve palsy in the setting of multiple vasculopathic risk factors. Treatable skull base lesions, including plasmacytoma and multiple myeloma, must be considered in patients with sixth nerve palsies, especially among those who demonstrate a progressive course or multiple cranial neuropathies.

Gold-Catalyzed Synthesis of Substituted 3-Trifluoromethylpyrroles from Mesylated Amino Trifluoromethylpropargylic Alcohols. A series of substituted 3-trifluoromethylpyrroles was obtained from trifluoromethylamino-ynol derivatives via a gold-catalyzed cyclization. Using fluorinated starting materials, after mesylation, allowed for the desired compounds to be obtained in good yields under mild conditions.

[Effect of TNF-alpha and MMP-9 in the infiltration of eosinophil granulocyte in nasal polyps]. To study the expression and significance of TNF-alpha, MMP-9 and their relationship with the infiltration of eosinophil granulocyte in nasal polyps. The expression of TNF-alpha and MMP-9 was determined in tissues of nasal polyps from 30 patients(nasal polyps group) and in inferior turbinate mucosa tissues from 10 patients(control group) by in situ hybridization and immunohistochemical technique, and the number of eosinophil granulocyte was counted in the same tissue by HE staining. Their correlations with each other were also analyzed in the tissue of nasal polyps. The number of TNF-alpha and MMP-9 positive cells and TNF-alpha positive blood vessels in nasal polyps were more than that in control group (P < 0.05). The number of both TNF-alpha positive cells and blood vessels had positive relationships with the number of eosinophil granulocyte, but there was only positive relationship between the number of MMP-9 positive cells and eosinophil granulocyte (P < 0.05). At the same time there was a positive relationship between the number of TNF-alpha and MMP-9 positive cells (P < 0.05). TNF-alpha and MMP-9 may play an important role in the pathological mechanism of nasal polyps. TNF-alpha may induce the expression of MMP-9 and promote the migration of eosinophil granulocyte.

Matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases mRNA transcripts in the bronchial secretions of asthmatics. Asthma is a chronic inflammatory disease characterized by profound extracellular matrix changes referred to as bronchial remodelling. In this study, we evaluated matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) mRNA expression in bronchial secretions of asthmatics and correlated MMPs modulations with the lung function as a reflection of the bronchial extracellular matrix remodelling. Quantitative RT-PCR was performed on cell pellets obtained from induced sputum in order to detect the mRNAs for MMP-1, -2, -3, -8, -9, -12, -13 TIMP-1, -2, while semiquantitative RT-PCR was performed to assess the expression of MMP-7, monocyte chemoattractant protein-1 (MCP-1) and transforming growth factor-beta(1) (TGF-beta(1)). The mRNA transcripts for MMP-1, TIMP-1 and monocyte chemoattractant protein-1 (MCP-1) were increased in cell pellets of induced sputum from asthmatics when compared to controls (P<0.05), and the intensity of MMP-1 mRNA expression inversely correlated with the FEV(1) in asthmatics (r=-0.49, P<0.05). The MMP-1 mRNA/TIMP-1 mRNA ratio correlated with the levels of MCP-1 mRNA in asthmatics (r=0.47, P<0.05). There were no differences between the groups with respect to mRNA coding for MMP-2, -3, -7, -8, -9, -12, -13, -14, TIMP-2 and TGF-beta(1). We conclude that cells contained in the bronchial secretions from asthmatics express higher amounts of mRNA for MMP-1 and TIMP-1, perhaps related to an increased expression of MCP-1, which might contribute to the extracellular matrix changes observed during airway remodelling.

Minimally invasive robotically assisted repair of atrial perforation from a pacemaker lead. We present the first reported case of robotic-assisted right atrial perforation repair and pacemaker lead extraction. A 75-year-old female with symptomatic sinus node dysfunction underwent atrial single chamber permanent pacemaker insertion via a persistent left superior vena cava approach. At one week follow-up a chest radiograph and a computerized dynamic tomography demonstrated that the right atrial lead had perforated the right atrial free wall. The patient remained asymptomatic without signs of pericardial tamponade, however urgent repair was warranted. Utilizing the da Vinci robotic system (Intuitive Surgical Inc., Sunnyvale, California, USA), the pacer lead perforation was visualized, the lead retracted, and the right atrium repaired. The existing atrial lead was repositioned in the right atrial appendage. The patient's postoperative convalescence was uneventful, and she was discharged home on the third post-operative day. This case demonstrates the increasing clinical utilization of robotic-assisted technology in minimally invasive cardiac surgery.

Maximal static respiratory pressures in adults: normal values and their relationship to determinants of respiratory function. Assessment of respiratory muscle strength is done most directly by measuring maximal static inspiratory and expiratory mouth pressures (MIPS and MEPS, respectively). The available studies that report reference values of MIPS and MEPS, however, show ill-explained wide variability, not only between individuals but also between studies. This study of 106 normal white adults (60 women and 46 males, aged 16 to 79 yr) attempts to identify the anthropometric factors which best predict MIPS and MEPS. It was found that: 1) smoking does not affect MIPS and MEPS; 2) sex is a major determinant of MIPS and MEPS, as women reached 68 and 63%, respectively, of the male values; 3) within each sex, age is the major determinant of MIPS and MEPS, since body size factors such as height, weight and percent ideal body weight do not significantly improve the relationship between age and MIPS or MEPS. In both sexes, the pattern of change in pressures with age is different for MIPS and MEPS, suggesting different maturation processes for MIPS and MEPS. While MIPS is an inverse linear function of age (i.e. MIPS decreases with advancing age from early adulthood on), the relationship between MEPS and age is best described by a second degree polynomial (i.e. MEPS increases towards a peak in mid-life, after which it also decreases with age).(ABSTRACT TRUNCATED AT 250 WORDS)

Conventional MRI cannot predict survival in childhood diffuse intrinsic pontine glioma. Diffuse intrinsic pontine glioma (DIPG) of childhood has a dismal prognosis. Clinical trials of new agents are vital and it is essential that the correct endpoints and disease assessments are chosen. A retrospective review of magnetic resonance imaging (MRI) scanning in a pure population of DIPG was undertaken. Baseline diagnostic MRI findings included; local tumour extension in upper medulla (74%) or midbrain (62%), metastatic disease (3%), basilar artery encasement (82%), necrosis (33%), intratumoural haemorrhage (26%), hydrocephalus (23%) and dorsal exophytic component (18%). Post-treatment MRI scans demonstrated increases in; leptomeningeal metastatic disease (16%), cystic change/necrosis (48%), enhancement (72%) and intratumoural haemorrhage (32%). Response rates were calculated according to both RECIST (4%) and WHO (24%) criteria. No MRI parameter in either the diagnostic or response scans had prognostic significance. We recommend that currently primary endpoints for DIPG clinical trials should be overall or possibly progression free survival and that new advanced functional imaging techniques should be explored as possible surrogate markers for novel therapy activity rather than conventional MRI response criteria.

Brominated flame retardants and other polyhalogenated compounds in indoor air and dust from two houses in Japan. This study analyzed polyhalogenated compounds (PHCs) such as brominated flame retardants (BFRs) in indoor air and dust samples from two modern homes in Japan. Concentrations of polychlorinated biphenyls (PCBs) and 2,4,6-tribromophenol (2,4,6-TBP) in exhaust and indoor air of two houses were detected at 10(2)-10(3)pgm(-3) order, which were well above those in outdoor air. For dust samples, the detected polybrominated diphenyl ether (PBDE) and polybrominated dibenzo-p-dioxins/furan concentrations resembled values found in our past study. Interestingly, compared to PBDE concentrations, two orders of magnitude higher concentration (13000 ng g(-1)) was observed for hexabromocyclododecanes (HBCDs) in a dust sample from one house. Based on the calculation of air/dust partition ratio values (Kad), low Kad values (log Kad <or=0) were obtained for high brominated PBDEs (pentaBDEs - decaBDE), tetrabromobisphenol A (TBBPA), and HBCDs, although indoor air contained higher contents of low chlorinated PCBs, low brominated PBDEs, and 2,4,6-TBP. Attention should be given to exposure to 2,4,6-TBP through inhalation of air as well as dust ingestion. Results of X-ray fluorescence analysis show high bromine concentrations in curtain and roll screen samples possessing a high product loading factor. Furthermore, a preliminary estimation was made of the likely magnitude of inhabitants' exposure to PHCs via inhalation and dust ingestion in the two houses.

Cryopreservation of the model alga Ectocarpus (Phaeophyceae). The brown alga Ectocarpus has recently become the first fully sequenced multicellular alga and is an important biological model. Due to the large and growing number of Ectocarpus strains isolated and maintained by the research community, including increasing numbers of mutants, there is an urgent need for developing reliable, cost-effective long-term maintenance techniques. We report here that cryopreservation constitutes an attractive option in this respect, using a simple two-step protocol employing combined DMSO 10 percent (v/v) and sorbitol 9 percent (w/v) as cryoprotectants. This model organism appears to be remarkably robust and post-cryo recovery has been observed in all strains tested in this study. Cultures can be regenerated by the germination of cryopreserved zooids (spores), or the recovery of vegetative cells. In the latter case, dividing surviving cells may grow into the cell lumen of a neighbouring dead cell, eventually regenerating a phenotypically normal thalloidal structure.

Alpha 1-antitrypsin gene polymorphism related to respiratory system disease. Restriction fragment length polymorphism (RFLP) in the alpha 1-antitrypsin gene region was studied in relation to chronic obstructive airway disease (COAD) and pneumoconiosis. Genomic DNA of 122 studied subjects was digested with Hind III restriction endonuclease and hybridized with the alpha 1-antitrypsin gene probe. In eight patients with COAD an unusual 10-kb restriction fragment was found hybridizing with the probe. Three of 70 patients were homozygotes for this variant allele and 5 were heterozygotes, showing the presence of two fragments, 2.7 kb and 10 kb. The presence of 10-kb restriction fragment seems to be related to the early development of COAD in studied subjects and therefore might be used as a genetic marker of the disease.

Live Imaging of Pathological Tau Protein and Tau Antibodies in a Neuron-Like Cellular Model. Several tau antibody therapies are now in clinical trials and numerous other tau antibodies are in various stages of preclinical development to treat Alzheimer's disease and related tauopathies. This involves long-term studies in mouse models that are necessary but time consuming and typically provide only a limited mechanistic understanding of how the antibodies work and why some are not effective. Live cellular imaging with fluorescently tagged pathological tau proteins and tau antibodies provides a valuable insight into their dynamic interaction outside or within the cell. Furthermore, this acute technique may have predictive validity to assess the potential efficacy of different tau antibodies in neutralizing and/or clearing tau aggregates, and can likely be applied to other amyloid diseases. Overall, it should facilitate identifying candidate antibodies for more detailed long-term validation. Due to the human origin of the model, it may be particularly useful to characterize humanized antibodies that utilize receptor-mediated uptake to reach their intracellular target.

General condition biomarkers in relation to contaminant burden in European flounder (Platichthys flesus). In respect to the differences found for vitellogenin (VTG) expression in male and immature flounder, general biological aspects and a set of chemical residues in the liver were compared between flounder from the Mersey and Dee estuaries (UK). Except for alpha-HCH, all pollutant chemicals analysed in flounder liver differed highly significantly between Mersey and Dee fish. Overall, the higher liver contaminant concentrations were found in VTG-induced Mersey flounder. The biomarkers studied were not found to indicate significant differences between Mersey and Dee fish. However, when all of the minor differences are taken into consideration, it appears that the slightly lower growth rates after age 2 in Mersey flounder, lower gonadosomatic index in both mature male and female animals, less precise seasonal patterns of condition factor (CF), hepatosomatic index and gonadosomatic index, and lower CF in immature Mersey fish may well be signs of a contaminant-affected Mersey population.

What do we really know about dark energy? In this paper, we discuss what we truly know about dark energy. I shall argue that, to date, our single indication for the existence of dark energy comes from distance measurements and their relation to redshift. Supernovae, cosmic microwave background anisotropies and observations of baryon acoustic oscillations simply tell us that the observed distance to a given redshift z is larger than the one expected from a Friedmann-Lemaître universe with matter only and the locally measured Hubble parameter.