Identification of Two Brassinosteroids from the Cambial Region of Scots Pine (Pinus silverstris) by Gas Chromatography-Mass Spectrometry, after Detection Using a Dwarf Rice Lamina Inclination Bioassay.
A simple and improved dwarf rice (Oryza sativa var Tan-ginbozu) lamina inclination bioassay for brassinosteroids (BRs) was developed based on a previously published method (K Takeno, RP Pharis [1982] Plant Cell Physiol 23: 1275-1281). The assay used 3-day-old intact seedlings, and detection of BR was made more sensitive by synergizing the response to BR with indole-3-acetic acid (IAA). The minimum detectable amount of BR was less than 0.1 nanogram/rice plant (brassinolide equivalents). Purification steps for isolation of BR from tissue scrapings taken from the cambial region of Scots pine (Pinus silverstris) harvested during the period of rapid wood production were guided by this assay. After column chromatography (silica gel and PrepPak C(18)) and reversed phase C(18) high performance liquid chromatography, the biologically active fractions were analyzed by gas chromatography-mass spectrometry (GC-MS) and/or GC-MS-selected ion monitoring. Two BRs, castasterone (major) and brassinolide (minor) were identified. This is the first identification of BR from the cambial region of a conifer.


Methyl beta-D-galactopyranosyl-(1-->4)-beta-D-allopyranoside tetrahydrate.
The title compound, C(13)H(24)O(11).4H(2)O, (I), crystallized from water, has an internal glycosidic linkage conformation having phi' (O5(Gal)-C1(Gal)-O1(Gal)-C4(All)) = -96.40 (12) degrees and psi' (C1(Gal)-O1(Gal)-C4(All)-C5(All)) = -160.93 (10) degrees , where ring-atom numbering conforms to the convention in which C1 denotes the anomeric C atom, C5 the ring atom bearing the exocyclic hydroxymethyl group, and C6 the exocyclic hydroxymethyl (CH(2)OH) C atom in the betaGalp and betaAllp residues. Internal linkage conformations in the crystal structures of the structurally related disaccharides methyl beta-lactoside [methyl beta-D-galactopyranosyl-(1-->4)-beta-D-glucopyranoside] methanol solvate [Stenutz, Shang & Serianni (1999). Acta Cryst. C55, 1719-1721], (II), and methyl beta-cellobioside [methyl beta-D-glucopyranosyl-(1-->4)-beta-D-glucopyranoside] methanol solvate [Ham & Williams (1970). Acta Cryst. B26, 1373-1383], (III), are characterized by phi' = -88.4 (2) degrees and psi' = -161.3 (2) degrees , and phi' = -91.1 degrees and psi' = -160.7 degrees , respectively. Inter-residue hydrogen bonding is observed between O3(Glc) and O5(Gal/Glc) in the crystal structures of (II) and (III), suggesting a role in determining their preferred linkage conformations. An analogous inter-residue hydrogen bond does not exist in (I) due to the axial orientation of O3(All), yet its internal linkage conformation is very similar to those of (II) and (III).


An Optimal Approach for Selecting Discriminant Regions for the Diagnosis of Alzheimer's Disease.
In this work, we present a fully automatic computer-aided diagnosis method for the early diagnosis of the Alzheimer's disease. We study the distance between classes (labelled as normal controls and possible Alzheimer's disease) calculated in 116 regions of the brain using the Welchs's t-test. We select the regions with highest Welchs's t-test value as features to perform classification. Furthermore, we also study the less discriminative region according to the t-test (regions with lowest t-test absolute values) in order to use them as reference. We show that the mean and standard deviation of the intensity values in these two regions, the less and most discriminative according to the Welch's ttest, can be combined as a vector. The modulus and phase of this vector reveal statistical differences between groups which can be used to improve the classification task. We show how they can be used as input for a support vector machine classifier. The proposed methodology is tested in a SPECT brain database of 70 SPECT brain images yielding an accuracy up to 91.5% for a wide range of selected voxels.


Comparison between off- and on-pump coronary artery bypass grafting: long-term results of a real-world registry.
The aim of this study was to compare 5-year rates of overall death, cardiac-related death, myocardial infarction, repeat revascularization, stroke and new occurrence of postoperative renal failure in a large cohort of patients with coronary disease, treated with on- or off-pump coronary artery bypass grafting (CABG). Two propensity score-matched cohorts, each of 560 patients, undergoing isolated surgical coronary revascularization at the regional public and private centres of Emilia-Romagna region (Italy) over the period 1 January 2003 - 31 December 2013, were used to compare long-term outcomes of on-pump CABG (6711 patients) and off-pump CABG (597 patients). The matched on-pump group received significantly more bypass grafts than the matched off-pump group (2.4 ± 1.1 vs 1.6 ± 0.9, P < 0.0001). The on-pump group reported statistically significant lower cardiac-related mortality. There was a trend towards higher overall mortality and the need for repeat revascularization procedures in the off-pump group. No difference was found for myocardial infarction, stroke or new occurrence of postoperative renal failure between groups in the follow-up. The multivariate analysis of significant predictors of mortality in the overall population confirmed that the off-pump revascularization strategy was an independent predictor of death at long-term follow-up. On-pump CABG reported significantly better results in terms of mortality in the subgroups of patients with a depressed left ventricular ejection fraction and in patients with three-vessel disease. In patients undergoing elective isolated CABG, on-pump strategy conferred a long-term survival advantage compared with off-pump strategy, particularly for patients with more extensive coronary disease. No benefits were found in terms of reduction of postoperative morbidity with the off-pump strategy. On-pump surgery should be the preferred revascularization technique, and off-pump surgery reserved for patients for whom the perioperative risk of cardiopulmonary bypass is greater than the risk of a less complete coronary revascularization.


Identification of genetic loci associated with fire blight resistance in Malus through combined use of QTL and association mapping.
Fire blight, incited by the enterobacterium Erwinia amylovora, is a destructive disease of Rosaceae, particularly of apples and pears. There are reports on the molecular mechanisms underlying E. amylovora pathogenesis and how the host activates its resistance mechanism. The host's resistance mechanism is quantitatively controlled, although some major genes might also be involved. Thus far, quantitative trait loci (QTL) mapping and differential expression studies have been used to elucidate those genes and/or genomic regions underlying quantitative resistance present in the apple genome. In this study, an effort is undertaken to dissect the genetic basis of fire blight resistance in apple using both QTL and genome-wide association mapping. On the basis of an F1 pedigree of 'Coop 16' × 'Coop 17' and a genome-wide association study (GWAS) mapping population of Malus accessions (species, old and new cultivars and selections), new QTLs and associations have been identified. A total of three QTLs for resistance to fire blight, with above 95% significant logarithm of odds threshold value of 2.5, have been identified on linkage groups (LGs) 02, 06, and 15 of the apple genome with phenotypic variation explained values of 14.7, 20.1 and 17.4, respectively. Although elevated P-values with signals for marker-trait associations are observed for some LGs, these are not found to be significant. However, a total of 34 significant associations, with P-values ≥0.02, have been detected including 8 for lesion length at 7 days following inoculation (PL1), 14 for lesion length at 14 days following inoculation (PL2), and 12 for shoot length.


[Treatment with iloprost of critical ischemia of the lower limbs associated with cardiac insufficiency. Study of interaction with the pharmacokinetics of digoxin].
We have treated with intravenous iloprost twelve patients suffering from cardiac insufficiency compensated under oral digoxin (NYHA class II) associated with severe limb ischaemia due to arterial insufficiency. Our aim was to study its possible interaction on digoxin levels and to evaluate the long-term efficacy of iloprost. Although iloprost slowed the digoxin absorption by approximately one hour, we found no clinically significant difference between the digoxin pharmacokinetic data before and during treatment by iloprost. Moreover, 11 out of the 12 patients had a good clinical fate after the treatment, which persisted at 6 months. The pain disappeared in 4 and diminished in 7; and all skin ulcers healed. This improvement has lasted up to two and a half years in two patients. The clinical tolerance of iloprost was acceptable despite frequent headache and flushing associated with hypotension and nausea. We conclude that iloprost seems to be a very promising treatment of severe limb ischaemia when no intervention on the proximal arteries is possible. The patients on digoxin can continue their treatment without dose alteration while starting on iloprost.


Azithromycin modulates release of steroid-insensitive cytokines from peripheral blood mononuclear cells of patients with chronic obstructive pulmonary disease.
Oxidative stress reduces responsiveness of peripheral blood mononuclear cells (PBMCs) from patients with chronic obstructive pulmonary disease (COPD) to the anti-inflammatory effects of glucocorticoids (GCs). Azithromycin was shown to modulate corticosteroid resistance mechanisms in COPD patients. However, its ability to enhance anti-inflammatory properties of GCs on the production of cytokines by PBMCs has not well been elucidated. Heparinised blood was collected from 27 patients with COPD. Phytohaemagglutinin-induced release of pro-inflammatory mediators from PBMCs and production of intracellular cytokines by CD4+ and CD8+ T cells stimulated with phorbol 12-myristate 13-acetate and ionomycin in the presence or absence of 10 μg/mL azithromycin and 10 nM budesonide were determined using enzyme linked immunosorbent assay and flow cytometry. Azithromycin decreased the secretion of interleukin (IL) 4, IL-5, IL-13, and IL-17A from PBMCs, as well as the production of IL-4 and IL-8 by CD4+ and CD8+ T cells. The combination of azithromycin and budesonide suppressed inflammatory response by inhibition of IL-4, IL-5, IL-8, IL-13, IL-17A, IL-33, thymic stromal lymphopoietin (TSLP), macrophage migration inhibitory factor (MIF) release from PBMCs and by reduction of the percentage of IL-4-, IL-8-, interferon γ- and tumor necrosis factor a-expressing CD4+ and CD8+ T cells. The inhibitory effect of azithromycin combined with budesonide on IL-4, IL-5, IL-8, IL-17A, TSLP production by PBMCs, as well as IL-4 and IL-8 production by T helper cells and cytotoxic T lymphocytes was significantly greater than the effect of budesonide alone. Azithromycin in combination with budesonide enhances GC properties by inhibiting synthesis of pro-inflammatory cytokines in blood cells of COPD patients.


Enhanced spontaneous Raman scattering and gas composition analysis using a photonic crystal fiber.
Spontaneous gas-phase Raman scattering using a hollow-core photonic bandgap fiber (HC-PBF) for both the gas cell and the Stokes light collector is reported. It was predicted that the HC-PBF configuration would yield several hundred times signal enhancement in Stokes power over a traditional free-space configuration because of increased interaction lengths and large collection angles. Predictions were verified by using nitrogen Stokes signals. The utility of this system was demonstrated by measuring the Raman signals as functions of concentration for major species in natural gas. This allowed photomultiplier-based measurements of natural gas species in relatively short integration times, measurements that were previously difficult with other systems.


The Cedar Project: Racism and its impacts on health and wellbeing among young Indigenous people who use drugs in Prince George and Vancouver, BC.
Racism continues to drive health disparities between Indigenous and non-Indigenous peoples in Canada. This study focuses on racism experienced by young Indigenous people who have used drugs in British Columbia (BC), and predictors of interpersonal racism. Cedar Project is a community-governed cohort study involving young Indigenous people who use drugs in Vancouver and Prince George, BC. This cross-sectional study included data collected between August 2015-October 2016. The Measure of Indigenous Racism Experiences (MIRE) scale was used to assess experiences of interpersonal racism across 9 unique settings on a 5-point Likert scale, collapsing responses into three categories (none/low/high). Multinomial logistic regression models were used to examine associations between key variables and interpersonal racism. Among 321 participants, 79% (n = 255) experienced racism in at least one setting. Thirty two percent (n = 102) experienced high interpersonal racism from police, governmental agencies (child 'welfare', health personnel), and in public settings. Ever having a child apprehended (AOR:2.76, 95%CI:1.14-6.65), probable post-traumatic stress (AOR:2.64; 95%CI:1.08-6.46), trying to quit substances (AOR:3.69; 95%CI:1.04-13.06), leaving emergency room without receiving treatment (AOR:3.05; 95%CI:1.22-7.64), and having a traditional language spoken at home while growing up (AOR:2.86; 95%CI:1.90-6.90) were associated with high interpersonal racism. Among women, experiencing high interpersonal racism was more likely if they lived in Prince George (AOR:3.94; 95%CI:1.07-14.50), ever had a child apprehended (AOR:5.09; 95%CI:1.50-17.30), and had probable post-traumatic stress (AOR:5.21; 95%CI:1.43-18.95). Addressing racism experienced by Indigenous peoples requires immediate structural systemic, and interpersonal anti-racist reforms.


The study of interactive effects of pollutants: a biomarker approach.
Biochemical biomarkers, such as inhibition of serum butyryl cholinesterase (BuChE) and brain acetyl cholinesterase (AChE), have been useful in studies of interactive effects of pesticides in birds. Examples of interactions due to increased activation or decreased detoxication are reviewed. Studies have shown that hybrid red-legged partridges (Alectoris rufa cross) pretreated with the inducing ergosterol biosynthesis inhibiting (EBI) fungicide, prochloraz, were more sensitive to the toxic effects of the organophosphorous (OP) insecticide, malathion, than controls. A dose of 90 mg/kg prochloraz produced greater inhibition at 1, 4 and 24 h following oral administration of 50 mg/kg malathion, compared to corn oil controls. Pigeons (Columba livia) given 180 or 90 mg/kg prochloraz showed greater inhibition of BuChE activity following malathion administration than did control birds. Starlings (Stumus vulgaris), however, appeared not to be induced by 180 or 300 mg/kg prochloraz, and no difference in BuChE activity following dosing with malathion was apparent in comparison with controls. Other EBIs and OP combinations have been investigated in the partridge. Birds pretreated with prochloraz showed a trend towards greater inhibition of serum BuChE activity at most time points following dosing with the OPs dimethoate and chlorpyriphos. Birds pretreated with the EBI penconazole showed significantly greater inhibition of serum BuChE activity at 1, 4 and 24 h after malathion administration than did controls. The mechanism of increased activation of malathion due to induction of cytochrome P-450 by prochloraz is reviewed. In the case of interactions due to inhibition of detoxication, inhibition of brain AChE activity was a useful biochemical biomarker.(ABSTRACT TRUNCATED AT 250 WORDS)


Dynamic changes in the distribution of cytoplasmic myosin during Drosophila embryogenesis.
Dramatic changes in the localization of conventional non-muscle myosin characterize early embryogenesis in Drosophila melanogaster. During cellularization, myosin is concentrated around the furrow canals that form the leading margin of the plasma membrane as it plunges inward to package each somatic nucleus into a columnar epithelial cell. During gastrulation, there is specific anti-myosin staining at the apical ends of those cells that change shape in regions of invagination. Both of these localizations appear to result from a redistribution of a cortical store of maternal myosin. In the preblastoderm embryo, myosin is localized to the egg cortex, sub-cortical arrays of inclusions, and, diffusely, the yolk-free periplasm. At the syncytial blastoderm stage, myosin is found within cytoskeletal caps associated with the somatic nuclei at the embryonic surface. Following the final syncytial division, these myosin caps give rise to the myosin rings observed during cellularization. These distributions are observed with both whole immune serum and affinity-purified antibodies directed against Drosophila non-muscle myosin heavy chain. They are not detected in embryos stained with anti-Drosophila muscle myosin antiserum or with preimmune serum. Although immunolocalization can only suggest possible function, these myosin localizations and the coincident changes in cell morphology are consistent with a key role for non-muscle myosin in powering cellularization and gastrulation during embryogenesis.


Is 18F-FDG PET/CT useful for the early prediction of histopathologic response to neoadjuvant erlotinib in patients with non-small cell lung cancer?
Early prediction of treatment response is of value in avoiding the unnecessary toxicity of ineffective treatment. The objective of this study was to prospectively evaluate the role of integrated (18)F-FDG PET/CT for the early identification of response to neoadjuvant erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor. From October 2006 to March 2009, 23 patients with non-small cell lung cancer eligible for surgical resection were evaluated for this study. Patients received preoperative erlotinib (150 mg) once daily for 3 wk. (18)F-FDG PET/CT was performed before and at 1 wk after the administration of erlotinib. Changes in tumor (18)F-FDG uptake during treatment were measured by standardized uptake values and assessed prospectively according to the criteria of the European Organization for Research and Treatment of Cancer. Patients with a decrease in standardized uptake values of 25% or more after 1 wk were classified as "metabolic responders." The metabolic response was compared with the pathologic response, obtained by histopathologic examination of the resected specimen. Following the (18)F-FDG PET/CT criteria of the European Organization for Research and Treatment of Cancer, 6 patients (26%) had a partial response within 1 wk, 16 patients (70%) had stable disease, and 1 patient (4%) had progressive disease. The median percentage of necrosis in the early metabolic responder group was 70% (interquartile range, 30%-91%), and the median percentage of necrosis in the nonresponder group was 40% (interquartile range, 20%-50%; P = 0.09). The kappa-agreement between the metabolic and pathologic responders was 0.55 (P = 0.008). The results of this study suggest that early during the course of epidermal growth factor receptor tyrosine kinase inhibitor therapy, (18)F-FDG PET/CT can predict response to erlotinib treatment in patients with non-small cell lung cancer.


Second cancers in patients with chronic lymphocytic leukemia who received frontline fludarabine, cyclophosphamide and rituximab therapy: distribution and clinical outcomes.
Patients with chronic lymphocytic leukemia (CLL) are known to have an increased incidence of second cancers, but the contribution of commonly used frontline therapies to the incidence of second cancers is unclear. We report on the characteristics, incidence, outcomes and factors associated with second cancers in 234 patients receiving fludarabine, cyclophosphamide and rituximab (FCR) based regimens in the frontline setting. The risk of second cancers was 2.38 times higher than the expected risk in the general population. Ninety-three patients (40%) had other cancers before and 66 patients (28%) after FCR. Rates of therapy related acute myeloid leukemia/myelodysplastic syndrome (t-AML/MDS) (5.1%) and Richter transformation (RT) (9%) were high, while solid tumors were not increased. Overall survival of patients with second cancers after frontline FCR was shorter (median of 4.5 years) compared to patients with and without prior cancers. Second cancer risk after frontline FCR is mainly due to high rates of t-AML/MDS and RT, and as speculated the survival of affected patients is shorter.


Structure of L-3-hydroxyacyl-coenzyme A dehydrogenase: preliminary chain tracing at 2.8-A resolution.
The conformation of L-3-hydroxyacyl-CoA dehydrogenase (EC 188.8.131.52) has been derived from electron-density maps calculated at 2.8-A resolution with phases obtained from two heavy-atom derivatives and the bound coenzyme, NAD. Like other dehydrogenases, 3-hydroxyacyl-CoA dehydrogenase is a double-domain structure, but the bilobal nature of this enzyme is more pronounced than has been previously observed. The amino-terminal domain, which comprises approximately the first 200 residues, is responsible for binding the NAD cofactor and displays considerable structural homology with the dinucleotide binding domains observed in other NAD-, NADP-, and FAD-dependent enzymes. The carboxyl-terminal domain, comprising the remaining 107 residues, appears to be all alpha-helical and bears little homology to other known dehydrogenases. The subunit-subunit interface in the 3-hydroxyacyl-CoA dehydrogenase dimer is formed almost exclusively by residues in the smaller helical domain. A difference map between the apo and holo forms of the crystalline enzyme has been interpreted in terms of the NAD molecule being bound in a typically extended conformation. The location of the coenzyme binding site, along with the structural homology to other dehydrogenases, makes it possible to speculate about the location of the binding site for the fatty acyl-CoA substrate.


Analyzing Effects of Provider Education and Management Approach to Pediatric Obesity.
African-Americans with hypertension continue to demonstrate poor blood pressure (BP) control and have markedly lower rates of hypertension self-management compared to non-African-Americans. Innovative and practical solutions such as mHealth technology are promising and can be leveraged to promote self-management of hypertension. Substantial evidence has demonstrated the importance of community support in improving patients' management of chronic illnesses. Unfortunately, such programs do not offer technology-based interventions (TBI) as a delivery method. Thus, this paper describes the design and rationale of an ongoing pilot study that incorporates TBI using a community-based participatory approach.


Oral microparticulate vaccine for melanoma using M-cell targeting.
Cancer vaccines are limited in their use, because of their inability to mount a robust anti-tumor immune response. Thus, targeting M-cells in the small intestine, which are responsible for entry of many pathogens, will be an attractive way to elicit a strong immune response toward particulate antigens. Therefore, in the present investigation, we demonstrated that efficient oral vaccination against melanoma antigens could be accomplished by incorporating the antigens in an albumin-based microparticle with a ligand AAL (Aleuria aurantia lectin) targeted specifically to M-cells. The oral microparticulate vaccine effectively protected the mice from subcutaneous challenge with tumor cells in prophylactic settings. The animals were vaccinated with antigen microparticles having a size range of around 1-1.25 µm where one prime and four booster doses were administered every 14 days over 10 weeks of duration, followed by challenge with live tumor cells, which showed complete tumor protection after oral vaccination. With the inclusion of ligand in the microparticles, we observed significantly higher IgG titers (1565 μg/mL) as compared to the microparticle formulations without AAL (872 μg/mL). This data suggests that ligand loaded microparticles may have the potential to target antigens to M-cells for an efficient oral vaccination.


EEG/ERP evidence of possible hyperexcitability in older adults with elevated beta-amyloid.
Although growing evidence links beta-amyloid (Aβ) and neuronal hyperexcitability in preclinical mouse models of Alzheimer's disease (AD), a similar association in humans is yet to be established. The first aim of the study was to determine the association between elevated Aβ (Aβ+) and cognitive processes measured by the P3 event-related potential (ERP) in cognitively normal (CN) older adults. The second aim was to compare the event-related power between CNAβ+ and CNAβ-. Seventeen CNAβ+ participants (age: 73 ± 5, 11 females, Montreal Cognitive Assessment [MoCA] score 26 ± 2) and 17 CNAβ- participants group-matched for age, sex, and MOCA completed a working memory task (n-back with n = 0, 1, 2) test while wearing a 256-channel electro-encephalography net. P3 peak amplitude and latency of the target, nontarget and task difference effect (nontarget-target), and event-related power in the delta, theta, alpha, and beta bands, extracted from Fz, Cz, and Pz, were compared between groups using linear mixed models. P3 amplitude of the task difference effect at Fz and event-related power in the delta band were considered main outcomes. Correlations of mean Aβ standard uptake value ratios (SUVR) using positron emission tomography with P3 amplitude and latency of the task difference effect were analyzed using Pearson Correlation Coefficient r. The P3 peak amplitude of the task difference effect at Fz was lower in the CNAβ+ group (P = 0.048). Similarly, power was lower in the delta band for nontargets at Fz in the CNAβ+ participants (P = 0.04). The CNAβ+ participants also demonstrated higher theta and alpha power in channels at Cz and Pz, but no changes in P3 ERP. Strong correlations were found between the mean Aβ SUVR and the latency of the 1-back (r = - 0.69; P = 0.003) and 2-back (r = - 0.69; P = 0.004) of the task difference effect at channel Fz in the CNAβ+ group. Our data suggest that the elevated amyloid in cognitively normal older adults is associated with neuronal hyperexcitability. The decreased P3 task difference likely reflects early impairments in working memory processes. Further research is warranted to determine the validity of ERP in predicting clinical, neurobiological, and functional manifestations of AD.


Raman signature of graphene superlattices.
When two identical two-dimensional periodic structures are superposed, a mismatch rotation angle between the structures generates a superlattice. This effect is commonly observed in graphite, where the rotation between graphene layers generates Moiré patterns in scanning tunneling microscopy images. Here, a study of intravalley and intervalley double-resonance Raman processes mediated by static potentials in rotationally stacked bilayer graphene is presented. The peak properties depend on the mismatch rotation angle and can be used as an optical signature for superlattices in bilayer graphene. An atomic force microscopy system is used to produce and identify specific rotationally stacked bilayer graphenes that demonstrate the validity of our model.


Comparison of mammographic densities and their determinants in women from Japan and Hawaii.
Breast cancer incidence increases considerably in women who migrate from Japan to the United States. Based on the hypothesis that mammographic density in healthy mammograms reflects differences in breast cancer risk, we compared mammographic density in 3 groups of women at different levels of risk: Caucasian and Japanese women in Hawaii and Japanese women in Japan. In a cross-sectional design, pre- and postmenopausal women without a history of breast cancer and with a mammogram free of suspicious lesions were recruited in mammography clinics and completed a self-administered questionnaire. Cranio-caudal mammograms were scanned into a computer and the densities measured using a computer-assisted method. Statistical analyses included ANOVA and multiple linear regression. Breast size among women of Japanese ancestry was similar in Hawaii and Japan but 50% smaller than that among Caucasian women. Dense areas were smallest among women in Japan, intermediate among Japanese women in Hawaii and largest among Caucasian women. Percent densities were greater in Japanese women than Caucasian women because of the larger breast sizes in Caucasians. However, percent densities were significantly higher among Japanese women in Hawaii than in Japan. These results indicate that the size of the total breast differs primarily by ethnicity and the size of the dense areas differs mainly by place of residence. Therefore, when comparing ethnic groups with distinct physical proportions, the absolute size of the dense areas appears to be a better measure of breast cancer risk than the relative density.


Do investments in low-income neighborhoods produce objective change in health-related neighborhood conditions?
This study examined the effect of neighborhood investments on neighborhood walkability, presence of incivilities, and crime in two low-income, primarily African American neighborhoods in Pittsburgh, USA. During the study period, one of the neighborhoods (the intervention neighborhood) received substantially more publicly-funded investments than a demographically matched comparison neighborhood. Comparisons between the neighborhoods showed a significant difference-in-difference for all three outcomes. The intervention neighborhood experienced significantly more change related to improved walkability and decreased incivilities. However, the control neighborhood experienced better crime-related outcomes. Analyses that focused on resident proximity to investments found similar results. This highlights the nuances of neighborhood investment, which is important to consider when thinking about public policy.


Vaccination to Prevent Cancer.
Vaccines stimulate the immune system, mimicking infectious attacks and thereby promoting the development of protective antibodies and/or cellular immunity so that the body is immune to infection when live native infections attack. Some of these infections are associated with cancer-causing changes in the body; thus some vaccines may help prevent cancer.


The human lambda L chain Ig locus. Recharacterization of JC lambda 6 and identification of a functional JC lambda 7.
The human lambda L chain Ig gene complex consists of multiple JC gene segments. A seventh human lambda C region gene segment, C lambda 7, was found 2.7 kb downstream of C lambda 6 in this gene complex. A J lambda gene segment, J lambda 7, was found 1.2 kb upstream of C lambda 7 and contains potentially functional nonamer and heptamer recombination sites, an RNA splice site and J coding region. C lambda 7 maintains an open reading frame and encodes a new lambda isotype. C lambda 7 encodes Kern+ and Oz- determinants, but does not encode any of the Kern+Oz- myeloma proteins published to date. Nevertheless, we present evidence that JC lambda 7 is transcribed in normal lymphocytes and is functional. In contrast, we present new data that the C lambda 6 gene segment, reported by others to encode the Kern+Oz- protein, is non-functional due to a 4-bp insertion in our cosmid clone. The 4-bp insertion was characterized further in 32 genomic DNA samples by producing a distinctive restriction fragment length and verified by the DNA sequences of the polymerase chain reaction products of two different cell lines. We discuss the possibility that the Kern+Oz- myeloma proteins do not define an isotype and are not encoded by JC lambda 7 nor other non-allelic genes, and we discuss the level of expression of JC lamba 7 as compared to that of JC lambda 2 and JC lambda 3.


Two Cases of Granulomatous Mastitis Caused by Corynebacterium kroppenstedtii Infection in Nulliparous Young Women with Hyperprolactinemia.
Recently, an association between granulomatous mastitis and local infection with Corynebacterium (C.) kroppenstedtii has been suggested. We herein report two cases of granulomatous mastitis resulting from C. kroppenstedtii infection in nulliparous young women with hyperprolactinemia. Both cases involved nulliparous patients with drug-induced hyperprolactinemia, and both individuals received incision and drainage, after which the pus was sent to our laboratory. Corynebacterium spp. grew on blood agar, and 16S rRNA gene sequencing identified the pathogen as C. kroppenstedtii. In conclusion, lactational changes caused by drug-induced hyperprolactinemia may increase the risk of granulomatous mastitis after C. kroppenstedtii infection.


Structure-Based Discovery of Nonpeptide Allatostatin Analogues for Pest Control.
FGLamide allatostatins (ASTs) are regarded as possible insecticide candidates, although their lack of in vivo effects, rapid degradation, poor water solubility, and high production costs preclude their practical use in pest control. In contrast to previous research, the C-terminal tripeptide (FGLa) was selected as the lead compound in this study. Five nonpeptide AST analogues (2-amino-1-[3-oxo-3-(substituted-anilino)propyl]pyridinium nitrate derivatives) were designed on the basis of the structure-activity relationship and docking results of FGLa. All of the nonpeptide analogues (S1-S5) were more potent against juvenile-hormone (JH) biosynthesis than the lead compound. They significantly inhibited the biosynthesis of JH in vivo following injection. A pest-control application demonstrated that S1 and S3 have larvicidal effects following oral administration (the IC50 values were 0.020 and 0.0016 mg/g, respectively). The good oral toxicities and excellent water solubilities of S1 and S3 suggest that they have considerable potential as insecticides for pest management.


Effects of the selective alpha 1-antagonist, doxazosin, on hepatic lipid levels and metabolism in the golden hamster.
The effect of the selective alpha 1-antagonist, doxazosin, on lipid metabolism was studied in cholesterol-fed golden hamsters. The hamsters were studied after short-term (1 week) and long-term (6-8 weeks) treatment. Doxazosin was added to the food (0.05-0.1%). Doxazosin lowered, within 1 week, plasma cholesterol and triglyceride concentrations by 12 and 19%, respectively. These effects were slightly larger during long-term treatment (cholesterol by 15% and triglycerides by 27%). Lipoprotein lipase (LPL) activity in postheparin plasma or in adipose tissue or heart was affected by doxazosin. The hepatic triglyceride secretion rate was lowered by 40%. Doxazosin treatment partially prevented the accumulation of cholesterol and triglycerides in the liver. Hepatic cholesterol synthesis was decreased by 25-40%. When determined under optimal conditions, i.e., after prior dephosphorylation, the hepatic microsomal HMG-CoA reductase activity was lowered by 10-25% in the doxazosin-treated animals. However, if HMG-CoA reductase was determined under conditions to prevent phosphorylation and dephosphorylation of the enzyme, representing the in situ expressed activity, the activity in the doxazosin-treated animals was 40% lower than in the controls. These results indicate that the plasma lipid-lowering effect of doxazosin is largely due to its interference with hepatic lipid metabolism and that one of the effects is a lowering of hepatic cholesterol synthesis, probably due to an increase in the phosphorylation grade of HMG-CoA reductase.


Development of a new G-CSF product based on biosimilarity assessment.
Zarzio, a new recombinant human granulocyte colony-stimulating factor (filgrastim), was evaluated in healthy volunteers and neutropenic patients in phase I and III studies. Healthy volunteers in randomized, two-period crossover studies received single- and multiple-dose s.c. injections of 1 microg/kg (n = 24), 2.5 microg/kg (n = 28), 5 microg/kg (n = 28), or 10 microg/kg (n = 40), as well as single-dose i.v. infusions of 5 microg/kg (n = 26), of Zarzio or the reference product (Neupogen). Filgrastim serum levels were monitored; pharmacodynamic parameters were absolute neutrophil count (all studies) and CD34(+) cells (multiple-dose studies). Supportive efficacy and safety data were obtained from an open phase III study in 170 breast cancer patients undergoing four cycles of doxorubicin and docetaxel (Taxotere) chemotherapy, receiving Zarzio (300 or 480 microg) as primary prophylaxis of severe neutropenia. The results of the studies in healthy volunteers confirm the comparability of the test and reference products with respect to their pharmacodynamics and pharmacokinetics. Confidence intervals were within the predefined equivalence boundaries. In the phase III study in breast cancer patients, the administration of Zarzio was efficacious and safe, triggering no immunogenicity. The results of these studies demonstrate the biosimilarity of Zarzio with its reference product Neupogen.


Substituent influences on the stability of the ring and chain tautomers in 1,3-O,N-heterocyclic systems: characterization by 13C NMR chemical shifts, PM3 charge densities, and isodesmic reactions.
Substituent effects on the stabilities of the ring and chain forms in a tautomeric equilibrium of five series of 2-phenyloxazolidines or -perhydro-1,3-oxazines possessing nine different substitutions at the phenyl moiety have been studied with the aid of 13C NMR spectroscopy and PM3 charge density and energy calculations. Reaction energies of the isodesmic reactions, obtained from the calculated energies of formation, show that electron-donating substituents stabilize both the chain and ring tautomers but the effect is stronger on the stability of the chain form than on that of the ring form. The 13C chemical shift changes induced by the phenyl substituents (SCS) were analyzed by several different single and dual substituent parameter approaches. The best correlations were obtained by equation SCS = rhoFsigmaF + rhoRsigmaR. In all cases the rhoF values and in most cases also the rhoR values were negative at both the C=N and C-2 carbons, indicating a reverse behavior of the electron density. This concept could be verified by the charge density calculations. The 13C chemical shifts of the C=N and C-2 carbons show a normal dependence on the charge density (q(tot)), but the charge density shows a reverse dependence on substitution. Correlation analysis of the 13C chemical shifts, solvent effect (CDCl3 vs DMSO-d6) on the NMR behavior as well as the effect of substituents on the electron densities and on the stabilities of the ring and chain tautomers show that the substituent dependence of the relative stability of the ring and chain tautomers in equilibrium is governed by several different electronic effects. At least intramolecular hydrogen bonding between the imine nitrogen and the hydroxyl group as well as polarization of the C=N bond seem to contribute in the chain form. Stereoelectronic and electrostatic effects are possible to explain the increase in stability of the ring form by electron-donating substituents.


Efficacy and safety of QVA149 compared to the concurrent administration of its monocomponents indacaterol and glycopyrronium: the BEACON study.
The BEACON study evaluated the efficacy and safety of QVA149, a once-daily dual bronchodilator containing a fixed-dose combination of the long-acting β2-agonist (LABA) indacaterol and long-acting muscarinic antagonist (LAMA) glycopyrronium (NVA237), in development for the treatment of patients with chronic obstructive pulmonary disease (COPD), compared with the free-dose concurrent administration of indacaterol plus glycopyrronium (IND+GLY). In this multicenter, double-blind, parallel group study, patients with stage II or stage III COPD (Global initiative for chronic Obstructive Lung Disease [GOLD] 2010) were randomized (1:1) to once-daily QVA149 (110 μg indacaterol/50 μg glycopyrronium) or concurrent administration of indacaterol (150 μg) and glycopyrronium (50 μg) via the Breezhaler® device (Novartis AG, Basel, Switzerland) for 4 weeks. The primary endpoint was to evaluate the noninferiority of QVA149 as compared with concurrent administration of IND+GLY, for trough forced expiratory volume in 1 second (FEV1) after 4 weeks of treatment. The other assessments included FEV1 area under the curve from 0 to 4 hours (AUC0-4 hours) at day 1 and week 4, symptom scores, rescue medication use, safety, and tolerability over the 4-week study period. Of 193 patients randomized, 187 (96.9%) completed the study.Trough FEV1 at week 4 for QVA149 and IND+GLY was 1.5 L ± 0.02 [DOSAGE ERROR CORRECTED] and 1.46 L ± 0.18, respectively. The FEV1 AUC0-4 hours at day 1 and week 4 were similar between the two treatment groups. Both treatment groups had a similar reduction in symptom scores and rescue medication use for the 4-week treatment period. Overall, 25.6% of patients in QVA149 group and 25.2% in the IND+GLY group experienced an adverse event, with the majority being mild-to-moderate in severity. No deaths were reported during the study or during the 30 days follow-up period. The BEACON study demonstrated that once-daily QVA149 provides an efficacy and safety profile similar to the concurrent administration of its monocomponents indacaterol and glycopyrronium.


A comparative study of cadmium, lead, zinc, pH, and bulk density from the Enyigba lead and zinc mine in two different seasons.
Soil pH and bulk density, as well as the concentrations of cadmium (Cd), lead (Pb), and zinc (Zn) in soils and these metal levels in the leaves of cassava (Manihot esculenta) and rice (Oryza sativa), both collected, respectively, in the dry season (December) of 1991 and the rainy season (September) of 1992 from the Enyigba lead and zinc mine, Nigeria, were investigated. Interspecific variations in trace element levels in the plant leaves were detected and may reflect the predilection of these plants to particular elements rather than their variability being due to different climatic conditions, such as precipitation, or other environmental factors.


Variability of 24-hour voiding diary variables among asymptomatic women.
We determine whether urinary diary values are stable over time among women without lower urinary tract symptoms. Women without lower urinary tract symptoms completed a 24-hour log of fluid intake and volumes voided during June/July 2001 and again during February/March 2002. Initial and repeat diaries were compared using Wilcoxin signed rank tests, considered significant at the 5% level. A total of 137 subjects completed both diaries. Subjects voided a median of 8 times per 24 hours during the first and 7 per 24 hours during the second diary with 95% of subjects recording fewer than 13 voids per 24 hours during both diaries. Nighttime voids were recorded by 59 (43%) subjects during the first and 54 (39%) during the second diary. Urinary frequency and total urine volume were significantly greater during the first than second diary (Z = 2.1, p = 0.03 and Z = 3.3, p = 0.001, respectively). No significant differences in mean voided volume, maximum voided volume, voids per liter intake, total intake, or daytime or nighttime diuresis rates were found when the groups were compared. However, there were large individual differences in all diary variables. While there is large individual variation in diary values, pooled data from 24-hour urinary diaries concerning voids per liter intake, and mean and maximum voided volumes remain stable. Pooled data concerning raw urinary frequency and urine volumes may vary significantly without any treatment. When urinary frequency is of interest, the number of voids per liter intake may represent the most stable measure.


Bis-acenaphthoquinone diimides with high electron deficiency and good coplanar conformation.
A series of novel bis-acenaphthoquinone diimides featuring a highly electron-deficient bis-acenaphthoquinone core are facilely synthesized via Knoevenagel condensation reaction. The diimides show high electron deficiency and good coplanar conformation, together with one of them having a maximum electron mobility up to 0.038 cm2 V-1 s-1.


United Kingdom substance misuse treatment workers' attitudes toward 12-step self-help groups.
Research has highlighted the benefits of professional substance misuse treatment workers facilitating their clients' involvement in 12-step self-help groups such as Alcoholics Anonymous (AA) and Narcotics Anonymous (NA). This study used a cross-sectional survey design to explore the attitudes of substance misuse treatment staff working in the English West Midlands region toward AA and NA and the 12-step philosophy. A total of 346 treatment workers responded (71%). Fewer than 10% used the 12-step model in their treatment work, and only a third felt that their clients were generally suited to AA or NA. Fewer than half (46%) said that they were likely to recommend that their clients attend a self-help group meeting. Staff with nursing qualifications were more likely to have a positive attitude toward AA/NA than their non-nursing colleagues, and there was a statistically significant association between the level of reported spirituality of the workers and the likelihood of them recommending to clients that they attend AA or NA meetings. These results highlight differences in the role of AA/NA within the substance misuse treatment system in the United Kingdom and that in the United States; possible explanations are discussed.


3D Echocardiography Is More Efficient In Detail Assessment of Calcification in Chronic Rheumatic Mitral Stenosis.
Rheumatic heart disease is in the declining phase, with the increase of urbanization and increment of availability of healthcare facility. However still it causes a substantial number of morbidity and mortality in South Asia. The prevalence of Rheumatic Fever and Rheumatic heart disease in Bangladesh is still high, 0.6 and 0.3 per thousand populations respectively. In the rheumatic process mitral is the frequently involved valve, mostly in the form of mitral stenosis. Choice of a treatment modality and its success largely depend on the accurate assessment of severity of disease especially the extent and distribution of calcification. Echocardiography has a key role in the determination of the severity of mitral stenosis as well as assessment of details calcification. Conventionally 2 dimensional and Doppler echocardiography is used. Now a days, 3D echocardiography offers better cardiac imaging for detail evaluation. The heart being a complex structure, the 3D evaluation would certainly offer better imaging for the accurate assessment of the mitral stenosis, especially details of presence & distribution calcification. This cross-sectional observational study was done from May 2012 to October 2012 in University Cardiac Centre, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. Data were collected with informed written consent, from 50 subjects who underwent transthoracic 2D and 3D Echocardiography for the assessment of rheumatic mitral valve with special emphasis on accurate assessment of severity, extent and distribution of calcification. Precise measurement of MV area is essential in the assessment of severity, which is found comparable by both 2DE (0.98±0.24cm²) and 3DE (0.92±0.23cm²). But in identifying calcification and accurate assessment of severity, more importantly commissural involvement is better detected by 3DE (p=0.002). This has extreme importance in therapeutic decision making in the treatment of chronic rheumatic MS. So, to formulate an efficient management plan, three-dimensional echocardiography has promising prospects in detecting severity & extent of rheumatic calcification.


Availability of domiciliary dental care for the elderly.
PURPOSES OF THE INVESTIGATION: To find out if local nursing/residential home managers are experiencing any problems in obtaining domiciliary dental care for residents. To assess the availability of local GDS and CDS dentists for domiciliary dental care for the elderly and the range of treatments offered. Self-completing postal questionnaires distributed to 148 dentists and 80 nursing/residential home nurse managers. 71% of responding dentists undertook domiciliary visits but 43% of these were not accepting any new NHS domiciliary patients. Only 21% of those willing to visit would undertake any conservative treatment. Seventy per cent of nurse managers reported few problems in finding a NHS dentist, but the remaining 30% had found it difficult or impossible. Eighty-five per cent would find written guidelines helpful. The number of elderly patients keeping natural teeth is steadily increasing. The rate of dental caries in institutionalised patients is significantly higher than those living in their own homes. The number of dentists in the area of this study who are accepting new domiciliary patients is rapidly decreasing and only one in five will provide conservative treatment. This is a deteriorating situation, which merits further investigation on a national scale and subsequent planning to address it.


Expression of retinoic acid alpha and beta receptor genes in liver and hepatocellular carcinoma.
cDNA probes for human retinoic acid receptors alpha and beta (RAR alpha and RAR beta) were modified for use as specific hybridization probes to study hepatocellular carcinomas (HCC) and cell lines, liver regeneration, and fetal development. RAR beta mRNA was detected at low levels in adult liver and rose markedly during the early phase of liver regeneration. RAR beta mRNA was present at very low levels in HCC and was not detected in fetal liver. In contrast, RAR alpha mRNA was present at low levels in normal liver, but showed a marked elevation in several HCCs and cell lines. Growth of cell lines was altered by retinoic acid (RA), but the effects could not be predicted by the levels of either RAR alpha or RAR beta mRNA. However, the response correlated with cell phenotype. Three cell lines with an adult phenotype (high albumin and low alpha-fetoprotein) were inhibited by RA, two undifferentiated lines showed moderate growth stimulation, and two of three cell lines that had high levels of alpha-fetoprotein were markedly stimulated by RA.


Does Alexithymia Affect Memory for a Crime? The Relationship Between Alexithymia, Executive Functions, and Memories.
Prior studies on alexithymia and memory have found a negative association between the two constructs, especially when emotional memories are considered. Moreover, it has been demonstrated that also the executive functioning (EF) of the individuals influences this relationship. Thus, the goal of this study is to verify whether alexithymia can influence the memory accuracy for a violent crime in people with different levels of EF resources in terms of both correct details and memory distortions (i.e., omissions and commissions) reported. We assessed the alexithymia and EF resources of individuals and showed participants a video of a violent crime (i.e., murder). We then asked participants to testify about the content of the video by imagining to be witnesses of the crime. A memory test was run on two moments in time: immediately after the video presentation and after 10 days. Findings demonstrated that alexithymia influences the recall of the event both in proneness to report correct details and memory distortions of the participants (i.e., omissions and commissions). Additionally, we found a contribution of EF resources in this relationship. The findings provide new information for legal professionals on memory functioning.


The Anticancer Effects of the Pro-Apoptotic Benzofuran-Isatin Conjugate (5a) Are Associated With p53 Upregulation and Enhancement of Conventional Chemotherapeutic Drug Efficiency in Colorectal Cancer Cell Lines.
The present study aimed to investigate in-depth a cytotoxic novel benzofuran-isatin conjugate (5a, 3-methyl-N'-(2-oxoindolin-3-ylidene)benzofuran-2-carbohydrazide) with promising potential anticancer activities in colorectal adenocarcinoma HT29 and metastatic colorectal cancer (CRC) SW620 cell lines. Thus, the primary cell events involved in tumorigenicity, tumor development, metastasis, and chemotherapy response were explored. Both CRC cell lines were exposed to different concentrations of Compound 5a and then subjected to real-time cell viability, migration, and invasion assays, colony formation and cytotoxicity assays, and flow cytometry for cell cycle analysis and apoptosis determination. Western blot and RT-qPCR were performed to assess the protein and transcript expression levels of epithelial-mesenchymal transition (EMT), cell cycle, and apoptosis markers. We showed that the Compound 5a treatment exhibited anticancer effects through inhibition of HT29 and SW620 cell viability, migration, and invasion, in a dose-dependent manner, which were associated with the upregulation of the tumor suppressor p53. Compound 5a also inhibited the colony formation ability of HT29 and SW620 cells and reversed EMT markers E-cadherin and N-cadherin expression. CRC cell exposure to Compound 5a resulted in a cell cycle arrest at the G1/G0 phase in HT29 cells and at the G2/M phase in SW620 cells, along with the downregulation of cyclin A1 expression, described to be involved in the S phase entry. Furthermore, Compound 5a-induced apoptosis was associated with the downregulation of the anti-apoptotic Bcl-xl marker, upregulation of pro-apoptotic Bax and cytochrome c markers, and increased mitochondrial outer membrane permeability, suggesting the involvement of mitochondria-dependent apoptosis pathway. In addition, the combination studies of Compound 5a with the main conventional chemotherapeutic drugs 5-fluorouracil, irinotecan, and oxaliplatin showed a more potent cytotoxic effect in both CRC cells than a single treatment. In conclusion, our findings described the interesting in vitro anticancer properties of Compound 5a, shown to have possible antitumor, antimetastatic, and pro-apoptotic activities, with the enhancement of the cytotoxic efficiency of conventional chemotherapeutic drugs. In vivo studies are requested to confirm the promising anticancer potential of Compound 5a for CRC therapy.


[Fulminant hepatitis caused by disulfiram].
After undergoing withdrawal treatment for alcoholism as an in-patient for one year a 49-year-old woman was started on disulfiram, 250 mg daily, her liver function tests being normal. Except for vitamin B1 she received no further medication. Jaundice developed 13 days after onset of treatment and acute liver failure was diagnosed on the 18th day after a total disulfiram dose of 4.5 g (Quick value < 10%; bilirubin 460 mumol/l; GPT 5099 U/l; GOT 4142 U/l), as well as early renal failure (creatinine 300 mumol/l). An acute viral infection, autoimmune hepatitis and a metabolic liver disease were excluded by biochemical, serological and molecular biology tests. All toxicological tests were negative. The patient died 25 days after the onset of disulfiram treatment in hepatic coma due to a fulminant hepatitis with hepatorenal syndrome. Both a liver biopsy and the autopsy showed the signs of an acute hepatic dystrophy without cirrhosis. The temporal relationship between the disulfiram intake and onset of the illness, the exclusion of other causes of the fulminant hepatitis and the liver histology, which was compatible with a chemical-toxic hepatitis, indicate that this was a case of disulfiram-induced hepatitis. The hepatotoxicity of disulfiram is a very rare idiosyncratic reaction which is often fatal. Disulfiram administration must be discontinued at once if there is a rise in liver enzyme activity or jaundice occurs.


Stride-to-stride variability is altered during backward walking in anterior cruciate ligament deficient patients.
Recently backward walking is used by physical therapists to strengthen the hamstring muscles and thus improve the function of the knee joint of anterior cruciate ligament deficient patients. The aim of this study was to examine the stride-to-stride variability of anterior cruciate ligament deficient patients during backward walking. The variation of how a motor behavior emerges in time is best captured by tools derived from nonlinear dynamics, for which the temporal sequence in a series of values is the facet of interest. Fifteen patients with unilateral anterior cruciate ligament deficiency and eleven healthy controls walked backwards at their self-selected speed on a treadmill while three-dimensional knee kinematics were collected (100 Hz). A nonlinear measure, the largest Lyapunov Exponent was calculated from the resulted knee joint flexion-extension data of both groups to assess the stride-to-stride variability. Both knees of the deficient patients exhibited significantly lower Lyapunov Exponent values as compared to the healthy control group revealing more rigid movement pattern. The intact knee of the deficient patients showed significantly lower Lyapunov Exponent values as compared to the deficient knee. Anterior cruciate ligament (ACL) deficiency leads to loss of optimal variability regardless of the walking direction (forwards in previous studies or backwards here) as compared to healthy individuals. This could imply diminished functional responsiveness to the environmental demands for both knees of ACL deficient patients which could result in the knees being more susceptible to injury.


Clinical, cognitive, and neurophysiologic correlates of short-term treatment with carbamazepine, oxcarbazepine, and levetiracetam in healthy volunteers.
The adverse effects of the antiepileptic drugs (AEDs) originally developed are well known, while those of the newer AEDs remain unclear. To investigate clinical, cognitive, and neurophysiologic effects of carbamazepine, oxcarbazepine, and levetiracetam in healthy volunteers. A double-blind crossover study was conducted in 10 volunteers. Eight-day treatment with carbamazepine, oxcarbazepine, levetiracetam, or placebo was administered in random order. Drug doses were titrated gradually to the daily target doses on day 7: carbamazepine 800 mg, oxcarbazepine 1200 mg, and levetiracetam 1500 mg. At baseline and at the end of each treatment period, participants underwent cognitive and neurophysiologic assessment. A washout period of 14 days between treatment periods was conducted. More adverse events were self-reported with carbamazepine (63%) than the other treatments (oxcarbazepine 12%, levetiracetam 20%, placebo 5%; p < 0.001 between the 4 groups). Carbamazepine induced the greatest motor slowing (p = 0.002), followed by oxcarbazepine (p = 0.01). Levetiracetam left baseline motor speed unchanged. All AEDs increased attention span from baseline values as shown on the Stroop test. Quantitative electroencephalogram (EEG) analysis showed that carbamazepine significantly increased the delta-theta power and reduced the frequency of alpha rhythm; oxcarbazepine induced smaller changes than carbamazepine. Levetiracetam did not change any EEG measurements. On color visually evoked potential (VEP) tests, carbamazepine induced a constant slowing of P1 latency, while oxcarbazepine induced changes only after the blue-black pattern. All color VEP measures for volunteers receiving levetiracetam were almost unchanged. After short-term treatment in healthy volunteers, carbamazepine induced major clinical and neurophysiologic changes. Oxcarbazepine was better tolerated than carbamazepine. Levetiracetam interfered least with clinical and neurophysiologic test results.


[Analysis and thought on reaching the consensus during the development of acupuncture and moxibustion clinical practice guidelines in China].
Based on the 28 Chinese clinical practice guidelines of acupuncture and moxibustion, this study summarized and analyzed the contents related to reaching consensus during the development process. The results indicated that all the 28 guidelines reported they have used consensus in the "recommendations" section, and provided details on consensus personnel, consensus methods, consensus process and consensus materials. However, it was found that the reporting of consensus was in need of further improvement. The limitations included unclear definition and responsibilities of "expert group", obscure concept between "consensus meeting" and "expert discussion", non-rigorous process of reaching consensus when generating recommendations and lacking of detailed reporting of the consensus reaching process. As such, we suggested that future researchers should conduct researches to further standardized the consensus process when developing acupuncture and moxibustion clinical practice guidelines, so as to improve the quality and clinical applicability of guidelines..


Reporting vaccine-associated paralytic poliomyelitis: concordance between the CDC and the National Vaccine Injury Compensation Program.
This paper compares cases of paralytic poliomyelitis reported to the systems operated by the National Vaccine Injury Compensation Program and the Centers for Disease Control and Prevention (CDC) for reporting of adverse events associated with vaccination. Of the 118 cases of vaccine-associated paralytic poliomyelitis determined by either system, 18 were reported initially only to the compensation program, 50 only to the CDC, and 50 to both. The annual incidence of vaccine-associated paralytic poliomyelitis determined from data from both systems varied from 6 to 13 cases (mean = 9.1) a year, with an increase of 1.4 cases a year when initial reports only to the compensation program are included. Thus, the compensation program provides important supplemental incidence data.


Therapeutic mirror interventions: an integrated review of the literature.
The mirror is an object that shows one a reflected image of body areas. There appears to be limited nursing literature about the role of a nurse in the use of a mirror. There is, however, literature of the therapeutic use of mirrors in medicine, neurology, psychiatry, psychology, physical medicine and rehabilitation, and rheumatology. The objective of this article is to review the basic elements and the underlying theoretical framework of mirror interventions. In 2007 to 2008, a keyword, abstract, and title search was conducted for therapeutic mirror studies between the years 1998 and 2008. A multidisciplinary, integrated review approach was used when it became apparent that there were limited nursing studies. Qualitative and quantitative strategies for reviewing evidence were used, and a narrative synthesis approach was used to guide the comprehensive synthesis. Underlying theoretical models were identified, and five elements of mirror interventions were synthesized from the literature.


Forearm Fractures: Diagnosis and Contemporary Treatment Strategies.
Diaphyseal forearm fractures represent a spectrum of injury patterns that include isolated radial shaft fractures, isolated ulnar shaft fractures, both-bone forearm fractures, Galeazzi fracture-dislocations, and Monteggia fracture-dislocations. Although less common than distal radius fractures, diaphyseal forearm fractures are still a frequently encountered clinical entity seen by orthopaedic surgeons, both as isolated injuries and in the patient with polytrauma. It is important to review the epidemiology of diaphyseal forearm fractures and the classification systems used to describe them, as well as to discuss the principles of the initial evaluation and management of these fractures. It is important to know the indications for nonsurgical and surgical management, along with the goals of surgical management, options for internal fixation, and surgical approaches to the forearm.


Clinicians' views on conversations and shared decision making in diagnostic testing for Alzheimer's disease: The ABIDE project.
This study explores clinicians' views on and experiences with when, how, and by whom decisions about diagnostic testing for Alzheimer's disease are made and how test results are discussed with patients. Following a preparatory focus group with 13 neurologists and geriatricians, we disseminated an online questionnaire among 200 memory clinic clinicians. Respondents were 95 neurologists and geriatricians (response rate 47.5%). Clinicians (74%) indicated that decisions about testing are made before the first encounter, yet they favored a shared decision-making approach. Patient involvement seems limited to receiving information. Clinicians with less tolerance for uncertainty preferred a bigger say in decisions (P < .05). Clinicians indicated to always communicate the diagnosis (94%), results of different tests (88%-96%), and risk of developing dementia (66%). Clinicians favor patient involvement in deciding about diagnostic testing, but conversations about decisions and test results can be improved and supported.


Pan-cortical coordination underlying mental effort.
It is well known that activity in, or coordination among, brain regions, can underlie movement, sensation, language, and cognition but there are observations that tasks unrelated to specific brain regions can nonetheless alter activity in those regions. These tasks might invoke activity in multiregional networks, but it also is possible that they are associated with changes beyond these networks. We therefore evaluated the possibility that more widespread, or even whole-cortical, mechanisms might complement or alter focal or multifocal cortical activity. We assessed the extent of electroencephalographic changes occurring outside areas with epileptiform activity, but that were associated with termination of the epileptiform activity. To do this, we measured the distribution of wavelet cross-coherence changes based on electrocorticography from 15 patients who showed regional afterdischarges in response to electrical brain stimulation prior to epilepsy surgery and in whom cognitive tasks were used in attempts to end the afterdischarges. There were 1276 electrodes implanted in these patients, and we analyzed a total of 55,494 electrode combinations. We compared recordings when cognitive effort was versus when it was not successful in ending afterdischarges. We found that when afterdischarges were suppressed there were changes in electrocorticographic coherence that were similar throughout cortex, regardless of the distance between sites. The similarity implies coordination of the changes, and the similarity regardless of distance or location implies a pan-cortical effect. Our results provide physical support for hypotheses that pan-cortical processes complement the well-known regional and multiregional networks. These processes may participate in, be recruited by, modify, or underlie the conative experiences of waking life.


[Dynamics of the cellular immune reactions in precancer and cancer of the large intestine].
Ninety cases of colon precancer and cancer were examined histologically, histochemically and morphometrically from the viewpoint of cell immune reactions of local connective tissue and regional lymph nodes. It is found that the intensity of mutual cell responses of local connective tissue, colon lymph follicles and regional lymph nodes increases in parallel with the malignization of adenomatous polyps and villous adenomata, reaches a peak in the incipient carcinoma and rapidly decreases when the invasive growth starts. The correlation between the plasma cells and lymphoid cells changes, the relative density of the latter is the greatest in the incipient carcinoma. The data obtained may be used for the incipient carcinoma diagnosis and for prognosis.


Molecular dynamics study of diffusion in a bilayer electron gas.
Molecular dynamics simulations of strongly coupled, classical electronic bilayers, interacting through the Coulomb potential, have been produced and studied. Values of the plasma coupling parameter Gamma between 10 and 80 and interlayer separations d from 0.1 to 3.0, (in units of Wigner-Seitz radius), were considered. The simulation results were used to calculate the intralayer and interlayer pair correlation functions and self-diffusion of charged particles in this system. The variation of self-diffusion with Gamma and d has been analyzed, and it is found that for the largest value of Gamma, the diffusion coefficient does not increase monotonically with layer separation, but has a distinct minimum for values of d slightly less than 1.


[Additional contribution of high amplification electrocardiography in the follow-up of children with muscular dystrophy].
Fifteen children and adolescents with muscular dystrophy underwent investigation by Doppler echocardiography and high amplification electrocardiography to evaluate the quality of left ventricular function. High amplification ECG showed minor intra-atrial conduction defects in 3 cases and abnormal late micro potentials without arrhythmogenic late potentials in 3 other cases. Significant abnormalities were observed in 40% of children examined. Doppler echocardiography showed relative conservation of systolic left ventricular function but a decrease in indices of contractility was observed in 46% of cases, especially in patients with Duchenne muscular dystrophy. Abnormalities of left ventricular distensibility were observed earlier and were more common (53% of cases). A significant decrease in cardiac output was found in 50% of patients, especially among the older and more severely affected children irrespective of the type of muscular dystrophy. These two investigations provide complementary information for the evaluation of left ventricular function of children with muscular dystrophy and they are proposed routinely for the follow-up of these patients.


Thermosetting resins with high fractions of free volume and inherently low dielectric constants.
This work demonstrates a new class of thermosetting resins, based on Meldrum's acid (MA) derivatives, which have high fractions of free volume and inherently low k values of about 2.0 at 1 MHz. Thermal decomposition of the MA groups evolves CO2 and acetone to create air-trapped cavities so as to reduce the dielectric constants.


Heterogeneity of expression and secretion of native and mutant [AspB10]insulin in AtT20 cells.
AtT20 (pituitary corticotroph) cells were transfected with either the native or a mutant [AspB10]rat insulin II gene, using a plasmid containing the insulin gene and a neomycin resistance gene under the control of independent constitutive promoters. The cellular immunoreactive insulin (IRI) content ranged from 0.8-440 ng/10(6) cells, with the highest value similar to that found for a rat insulinoma cell line (RIN) and corresponding to approximately 1% that of native pancreatic B-cells. There was a direct correlation between insulin mRNA levels and IRI content and no correlation between mRNA levels and rat insulin II gene copy number. Furthermore, in some lines the insulin II transgene was lost even though the gene encoding neomycin resistance was retained. IRI release was stimulated up to 4-fold by isobutylmethylxanthine in all lines transfected with the native rat insulin II gene, and HPLC analysis showed most IRI as fully processed insulin, with less than 5% as proinsulin. These cells, thus, directed most proinsulin to secretory granules for conversion and regulated release regardless of the absolute amount of IRI expressed. One of the lines transfected with the AspB10 mutant gene (line AA9) released nearly 50% of IRI as proinsulin under basal conditions, with stimulation of insulin, but not proinsulin, release by isobutylmethylxanthine. This confirmed our previous finding of partial diversion of this mutant proinsulin from the regulated to the constitutive pathway. A second line (IC6) expressing the same mutant gene at much higher levels appeared to direct all mutant proinsulin to the regulated pathway, suggesting that for this particular mutant proinsulin, the secretory pathway employed by the transfected cells can be affected by the amount of proinsulin synthesized.


Charge Transport in LDPE Nanocomposites Part II-Computational Approach.
A bipolar charge transport model is employed to investigate the remarkable reduction in dc conductivity of low-density polyethylene (LDPE) based material filled with uncoated nanofillers (reported in the first part of this work). The effect of temperature on charge transport is considered and the model outcomes are compared with measured conduction currents. The simulations reveal that the contribution of charge carrier recombination to the total transport process becomes more significant at elevated temperatures. Among the effects caused by the presence of nanoparticles, a reduced charge injection at electrodes has been found as the most essential one. Possible mechanisms for charge injection at different temperatures are therefore discussed.


Molecular characterization of parthenogenic Fasciola sp. in Korea on the basis of DNA sequences of ribosomal ITS1 and mitochondrial NDI gene.
Nucleotide sequences of ribosomal internal transcribed spacer (ITS1) and mitochondrial NADH dehydrogenase I (NDI) gene were analyzed to genetically characterize aspermic Fasciola forms in Korea. From the difference in ITS1 sequences, Korean flukes were divided into 3 haplotypes represented by Kor1, Kor2 and Kor1/2, which had nucleotides identical to F. hepatica, F. gigantica and those overlapped between the two species, respectively. NDI sequences also showed that Korean flukes could be classified into 3 distinct haplotypes (Kor1: F. hepatica-type, Kor2a and Kor2b: F. gigantica-type). The sequences of Kor1 and Kor2a were 100% identical to those of the haplotypes Fsp1and Fsp2, respectively, which are major Fasciola forms in Japan. These findings strongly suggest that aspermic Fasciola forms in Korea and Japan originated from same ancestors and have recently spread throughout both countries.


Points for consideration: transferring and changing hospital clinical laboratories.
The laboratories of Carmel Medical Centre were located in the main hospital building since its establishment (1977). Due to expansion of the clinical wards, the laboratories were relocated to a nearby building. The project was utilized for reorganization of the laboratories. The basic design addressed the existing hospital needs based mainly on the original organization of the laboratories. The project allowed for the prospective organizational changes. The planning, design, and erection were performed by teams of the hospital and by outside parties, headed by the hospital management and the laboratories' director. The laboratories' staff was involved in all phases of the project. The project laid the foundations for future consolidation, i.e., establishment of a central reception station and merging of chemistry, endocrinology, pharmacology, and segments of immunology. The merging involved performance but not validation of tests. Separation between research and routine work was achieved. By-products attained were as follows: simplification of tube handling, reduction in volume of blood needed, improvements in safety, employees' amenities, general atmosphere, and communication within personnel. The successful transfer resulted from appropriate design, close cooperation between management and personnel, and the ability to pinpoint problems at early stages with ad hoc solutions.


Attitudes to bioethical issues: a case study of a screening project.
Commonly expressed in theoretical discussions about ethical problems in the context of epidemiology and screening is the need for more data. A study was carried out involving 21 explorative interviews with participant and nonparticipant mothers in a neonatal research screening project in progress in Sweden, ABIS (All Babies in Southeast Sweden). The respondents were asked, by way of open-ended questions, to give their opinions about certain ethical issues: informed consent; reasons for joining/declining; surrogate decision; the collection, analysis and storage of written and "live" material (biobanks); intervention etc. The ethical implications mentioned in the literature mostly concern the risk of creating distress and anxiety (anxiety and possible stigmatisation in respect of positive or false-positive results, worry about material collected and stored, distress caused by blood sampling procedures, etc.). Our results do not support the idea that the risks are substantial. The respondents rather indicate an attitude of benevolence--they are positive both to the current research on children, to the material they contribute (both written material and "biomaterial"), to possible results and intervention plans. On the other hand the participants expressed concern about the storage of material and the right to be informed of any screening/project results. Further studies in this field are needed and would be of help in theoretical discussion, the work of ethical committees and the designing of, for example, screening and research projects.


Evidences for a leaky scanning mechanism for the synthesis of the shorter M23 protein isoform of aquaporin-4: implication in orthogonal array formation and neuromyelitis optica antibody interaction.
Aquaporin-4 (AQP4) exists as two major isoforms that differ in the length of the N terminus, the shorter AQP4-M23 and the longer AQP4-M1. Both isoforms form tetramers, which can further aggregate in the plasma membrane to form typical orthogonal arrays of particles (OAPs) whose dimension depends on the ratio of the M1 and M23. In this study, we tested the hypothesis that the M23 isoform can be produced directly by the M1 mRNA. In cells transiently transfected with AQP4-M1 coding sequence we observed besides AQP4-M1 the additional presence of the AQP4-M23 isoform associated with the formation of typical OAPs observable by two-dimensional blue native/SDS-PAGE and total internal reflection microscopy. The mutation of the second in-frame methionine M23 in AQP4-M1 (AQP4-M1(M23I)) prevented the expression of the M23 isoform and the formation of OAPs. We propose "leaky scanning" as a translational mechanism for the expression of AQP4-M23 protein isoform and that the formation of OAPs may occur even in the absence of AQP4-M23 mRNA. This mechanism can have important pathophysiological implications for the cell regulation of the M1/M23 ratio and thus OAP size. In this study we also provide evidence that AQP4-M1 is mobile in the plasma membrane, that it is inserted and not excluded into immobile OAPs, and that it is an important determinant of OAP structure and size.


Hepatic progenitor cells in chronic hepatitis C: a phenomenon of older age and advanced liver disease.
Hepatic progenitor cells (HPC) appear in a variety of liver diseases. Their occurrence in chronic hepatitis C (CHC) remains unclear, and triggering factors have to be elucidated. The presence of HPC in CHC was examined in relation to histological and virological parameters and patient age. Fifty liver biopsies of HCV-infected patients were examined. The presence of HPC was evaluated by immunohistochemical expression of keratin 7 (K7). Double immunostaining with K7 and cell proliferation marker Ki-67 was undertaken. Ductular reaction at the limiting plate, mean number of isolated progenitor cells (IPC) and isolated ductular structures (IDS) were quantified. The predominant distribution pattern of IPC and IDS and the presence of K7(+) hepatocytes were registered. Relationship between ductular reaction, IPC, IDS, presence of K7(+) hepatocytes, and patient age, hepatitis grade and stage, HCV RNA, and HCV genotype was examined. Prominent ductular reaction and increased numbers of IPC and IDS correlated significantly with older age and severe fibrosis/cirrhosis. The above HPC subtypes were not proliferating. Periportal/periseptal distribution pattern of IPC and IDS and presence of K7(+) hepatocytes were significantly more frequent in advanced hepatitis stages and in patients older than 40 years. Intraparenchymal distribution pattern correlated with younger age, lobular activity, and early fibrosis stage. K7(+) hepatocytes were encountered almost exclusively in the periportal pattern and in the presence of interface hepatitis and were more frequent among HCV genotype-1 patients. HPC activation in CHC is a common but diverse phenomenon closely related to patient age and hepatitis stage.


Effects of spatial-frequency specific adaptation and target duration on visual persistence.
Two experiments investigated the properties of visual persistence as functions of spatial frequency, stimulus duration, and pattern-specific adaptation. In Experiment 1, increasing the duration of high spatial-frequency gratings from 50 to 500 msec decreased the duration of visual persistence produced by that grating to an asymptotic level. However, low-frequency gratings produced a constant estimate of visual persistence independent of presentation time. Also, spatial-frequency specific adaptation reduced the persistence of the high-frequency gratings to this asymptotic level, but the lower frequency persistence estimates already at this level were unaffected (Experiment 2). These findings are related to possible temporal properties of the sustained and transient visual systems.


[Management of renal calix calculosis].
A FREQUENT PROBLEM: Lithiases in the urinary tract form first in the calices, raising complex problems of lithogenesis. As described by Randall, in males caliceal lithiases are often composed of calcium oxalate, generally as a monohydrate. In females, calcium phosphate stones are common, stones related to urease-producing germs are less frequent, and the bi-hydrated form of calcium oxalate predominates. Caliceal lithiases can remain asymptomatic and are often discovered fortuitously. Symptoms include chronic lower back pain or urinary tract infections. Regular surveillance is required due to the risk of local growth into a more or less voluminous complex lithiasis. Misleading digestive tract or rhumatatism-like recurrent pain may result from local migration. Other stones descend spontaneously creating the specific problems of ureteral lithiasis. Consensus is still lacking on renal mapping, predominant chemical make-up, and measurement of caliceal lithiases. These three criteria must be carefully studied to achieve a rigorous widely-accepted classification scheme allowing comparisons between proposed management protocols. The classification should use simple and low-cost imaging techniques: plain x-rays remain the gold standard although spiral computed tomography provides a more complete, though more costly, analysis. Regular surveillance is indicated for asymptomatic caliceal lithases measuring less than 5 mm whatever the localization within the kidney. Symptomatic caliceal lithiases measuring less than 20 mm should be treated with first intention extracorporeal lithotripsy. Certain stones with known composition (cystine) resist external shock waves and certain lower or intradiverticular caliceal stones may require a more aggressive approach with percutaneous surgery or ureterorenoscopic endocorporeal lithotripsy. Combination treatment using percutaneous and extracorporeal techniques should be used for large stones (> 20 mm) or for stones lying in an abnormal urinary tract. The goal of all treatments for caliceal stones is to eliminate all residual fragments and collect all eliminated or extracted fragments for physical (intrared spectrophotometry) and non-chemical analysis of the different constituents to establish an adapted management scheme aimed at preventing recurrence.


Radiotherapy of cutaneous B cell lymphomas: our experience in 31 cases.
Since cutaneous B cell lymphomas belong mostly to low or intermediate histologic grade of malignancy and have low tendency to spreading, a local treatment such as radiotherapy appears to be a suitable choice in the management of the disease. The authors have reviewed their cases to verify this statement. 31 patients affected by cutaneous B cell lymphomas classified as IE stage according to Ann Arbor received radiotherapy with orthovoltage techniques with total doses per field ranging from 10 to 40 Gy (median dose 30 Gy). All the patients had a minimum follow-up of 2 years. All the target skin lesions underwent complete remission. In 10 patients (32.2%) the clinical remission is still lasting. In 21 cases (67.8%) a disease relapse was observed: only at skin in other sites than those previously treated in 17 (81%), at skin and lymph nodes in two cases (9.5%), at skin, bone, and lymph node in one case (4.7%), at skin and bowel in one case (4.7%). The extracutaneous involvement occurred in cases with lesions of intermediate grade malignancy. After a new course of radiotherapy for skin lesions only, and chemotherapy, surgery or megavoltage radiotherapy for the other involvements, on the whole 21 patients (67.8%) got a complete remission. On the basis of their results and of a review of the literature, the authors propose radiotherapy as the choice treatment of primary cutaneous B cell lymphomas.


Impaired Glymphatic Function and Pulsation Alterations in a Mouse Model of Vascular Cognitive Impairment.
Large vessel disease and carotid stenosis are key mechanisms contributing to vascular cognitive impairment (VCI) and dementia. Our previous work, and that of others, using rodent models, demonstrated that bilateral common carotid stenosis (BCAS) leads to cognitive impairment via gradual deterioration of the neuro-glial-vascular unit and accumulation of amyloid-β (Aβ) protein. Since brain-wide drainage pathways (glymphatic) for waste clearance, including Aβ removal, have been implicated in the pathophysiology of VCI via glial mechanisms, we hypothesized that glymphatic function would be impaired in a BCAS model and exacerbated in the presence of Aβ. Male wild-type and Tg-SwDI (model of microvascular amyloid) mice were subjected to BCAS or sham surgery which led to a reduction in cerebral perfusion and impaired spatial learning acquisition and cognitive flexibility. After 3 months survival, glymphatic function was evaluated by cerebrospinal fluid (CSF) fluorescent tracer influx. We demonstrated that BCAS caused a marked regional reduction of CSF tracer influx in the dorsolateral cortex and CA1-DG molecular layer. In parallel to these changes increased reactive astrogliosis was observed post-BCAS. To further investigate the mechanisms that may lead to these changes, we measured the pulsation of cortical vessels. BCAS impaired vascular pulsation in pial arteries in WT and Tg-SwDI mice. Our findings show that BCAS influences VCI and that this is paralleled by impaired glymphatic drainage and reduced vascular pulsation. We propose that these additional targets need to be considered when treating VCI.


Impact of obstructive sleep apnea on cardiac organ damage in patients with acute ischemic stroke.
Both obstructive sleep apnea (OSA) and cardiac organ damage have a crucial role in acute ischemic stroke. Our aim is to explore the relationship between OSA and cardiac organ damage in acute stroke patients. A total of 130 consecutive patients with acute ischemic stroke were enrolled. Patients underwent full multichannel 24-h polysomnography for evaluation of OSA and echocardiography to evaluate left ventricle (LV) mass index (LV mass/BSA, LV mass/height), thickness of interventricular septum (IVS) and posterior wall (LVPW), LV ejection fraction and left atrium enlargement. Information on occurrence of arterial hypertension and its treatment before stroke was obtained from patients' history. 61.9% (70) of patients, mostly men (67.1%), with acute stroke had OSA (AHI > 10). Patients with acute stroke and OSA showed a significant increase (P < 0.05) of LV mass index, IVS and LVPW thickness and a significant left atrial enlargement as compared with patients without OSA. LV ejection fraction was not significantly different in stroke patients with and without OSA and was within normal limits. No relationship was found among cardiac alterations, occurrence of OSA and history of hypertension. Acute stroke patients with OSA had higher LV mass and showed greater left atrial enlargement than patients without OSA. This study confirms the high prevalence of OSA in stroke patients, suggesting also an association between OSA and cardiac target organ damage. Our finding of structural LV abnormalities in acute stroke patients with OSA suggests a potential role of OSA as contributing factor in determining both cerebrovascular and cardiac damage, even in absence of clear link with a history of blood pressure elevation.


Comparative Proteomics of Dying and Surviving Cancer Cells Improves the Identification of Drug Targets and Sheds Light on Cell Life/Death Decisions.
Chemotherapeutics cause the detachment and death of adherent cancer cells. When studying the proteome changes to determine the protein target and mechanism of action of anticancer drugs, the still-attached cells are normally used, whereas the detached cells are usually ignored. To test the hypothesis that proteomes of detached cells contain valuable information, we separately analyzed the proteomes of detached and attached HCT-116, A375, and RKO cells treated for 48 h with 5-fluorouracil, methotrexate and paclitaxel. Individually, the proteomic data on attached and detached cells had comparable performance in target and drug mechanism deconvolution, whereas the combined data significantly improved the target ranking for paclitaxel. Comparative analysis of attached versus detached proteomes provided further insight into cell life and death decision making. Six proteins consistently up- or downregulated in the detached versus attached cells regardless of the drug and cell type were discovered; their role in cell death/survival was tested by silencing them with siRNA. Knocking down USP11, CTTN, ACAA2, and EIF4H had anti-proliferative effects, affecting UHRF1 additionally sensitized the cells to the anticancer drugs, while knocking down RNF-40 increased cell survival against the treatments. Therefore, adding detached cells to the expression proteomics analysis of drug-treated cells can significantly increase the analytical value of the approach. The data have been deposited to the ProteomeXchange with identifier PXD007686.


Inferior parietal lobule. Divergent architectonic asymmetries in the human brain.
Architectonic parcellation of the parietal lobes of eight human brains, with special attention paid to the inferior parietal lobule, resulted in a map that bore a close relationship to previous maps and took into consideration modern data on physiology and connections. Two general parietal zones were distinguished, one above and the other below the intraparietal sulcus, similar to the dorsal-ventral distinction suggested for the frontal lobe. Five areas were recognized in the inferior parietal lobule, of which areas parietal areas EG (PEG), G (PG), and occipitoparietal G (OPG) were in the angular gyrus. A lateralization toward the right was found for area PEG, an area structurally similar to the visually related cortices of the posterior superior parietal region. A lateralization toward the left was found for area PG, but only in brains with a larger left planum temporale. The asymmetry in area PG seemed to be linked to other asymmetries present in language areas, whereas the right-sided area PEG preponderance showed no relation to the language asymmetries.


MR imaging of slow axonal transport in vivo.
Three magnetopharmaceuticals based on a monocrystalline iron oxide nanocompound (MION) are evaluated as potential contrast agents for demonstrating axonal transport in vivo by magnetic resonance (MR) imaging. One agent has a strong positive charge, one has a strong negative charge, and the third is covalently linked to wheat germ agglutinin, a plant lectin with a high affinity for axon terminals. All three agents were tagged with rhodamine, and fluorescence microscopy was used to determine their fate after administration and to validate the imaging results. Following injection into or near various neural structures in the motor and visual systems of rats, MR images were obtained at multiple times up to 11 days later, and the imaged tissues were processed for subsequent histological examination. Similar results were obtained with all three agents. Axonal transport was not seen by MR imaging or fluorescence microscopy when the agents were injected into the calf muscles, the vitreous of the eye, or the superior colliculus. However, bidirectional axonal transport was shown unequivocally by both methods after injection directly into the site of a focal crush injury to the sciatic nerve. The nerve, which otherwise is isointense with surrounding tissues on MR images, appeared as a uniformly hypointense structure having a length approximately in proportion to the time from injection to imaging. By 11 days, the course of the nerve was traceable from its component roots in the cauda equina to its bifurcation into the tibial and common peroneal nerves in the leg. A transport rate of about 5 mm/day was calculated, which is consistent with the mechanism of slow transport. MION-based magnetopharmaceuticals thus can be used to demonstrate slow axonal transport, and thereby visualize peripheral nerves, in vivo by MR imaging.


Kinetics of anthocyanin degradation and browning in reconstituted blackberry juice treated at high temperatures (100-180 degrees C).
Monomeric anthocyanin degradation and nonenzymatic browning (NEB) index have been determined in reconstituted blackberry juice heated at high temperature in a hermetically sealed cell. Statistical analysis demonstrated that, when the temperature range (100-180 degrees C) was divided into two subranges (100-140 and 140-180 degrees C) for anthocyanin degradation, reaction kinetics were well represented by two sequential first-order reactions. The activation energy for NEB from 100 to 180 degrees C (106 kJxmol(-1)) was slightly higher than the anthocyanin value at the lower temperature range (92 kJxmol(-1)), but was more than twice the value for the higher range (44 kJxmol(-1)). The reaction rate constant at 140 degrees C for anthocyanin degradation (3.5 x 10(-3) s(-1)) was two times that for the NEB index (1.6 x 10(-3) s(-1)). Hence, anthocyanin degradation was faster than the appearance of NEB products. The non-isothermal method developed allows estimating kinetic parameters and thereby generating temperature profiles of heat processes that would help preserve the nutritional properties of foods during high-temperature processes.


[Retroperitoneal fibrosis secondary to metastatic neoplasm revealed by a leg lymphedema].
Diagnosis of retroperitoneal fibrosis is generally delayed and revealed by various non-specific signs. We report the case of an isolated lymphedema of the lower limb revealing retroperitoneal fibrosis complicating a metastatic squamous cell carcinoma. In an 83-year-old women, a lymphedema appeared that remained isolated for several months before being associated with alteration in general health. Morphological examinations showed bilateral compression of the urinary excretory tracts and led to the diagnosis of retroperitoneal fibrosis. Histological examination of a sub-clavicular adenopathy that had evolved over 9 months, confirmed the diagnosis of a metastatic squamous cell carcinoma of pulmonary cancer. Retroperitoneal fibrosis is an exceptional etiology that must be recognized in isolated lymphadomas of the lower limbs. In view of the possible tumoral origin of retroperitoneal fibrosis, any evocative sign accompanying the lymphedema must be searched for.


Allografts and xenografts for right ventricular outflow tract reconstruction in Ross patients.
Pulmonary allografts (AG) are the gold standard for right ventricular outflow tract (RVOT) reconstruction during the Ross procedure. However, there is limited availability of AG in some countries, and the use of alternative grafts for RVOT reconstruction remains controversial. This study aimed to compare the rates of freedom from RVOT graft dysfunction for AG and diepoxide-treated pericardial xenografts (DPXG). Between 1998 and 2015, 793 adult patients underwent the Ross procedure in our centre. Using propensity score matching, the clinical outcomes and echocardiographic results of AG and DPXG were compared. Propensity score matching resulted in 2 groups (AG and DPXG) of 122 patients each. No difference was found in early mortality (2.5%) in both groups. The freedom from RVOT graft dysfunction curves were comparable between the AG and DPXG groups (P = 0.186) and the 8-year rates of freedom from graft dysfunction were 91.8% and 82.2%, respectively. The survival rates at 8 years were 90.5% and 90.1%, and the rates of freedom from RVOT reintervention at 8 years were 100% and 96.8% for the AG and DPXG groups, respectively. At discharge and follow-up, transprosthetic gradients were significantly higher in the DPXG group. The rate of the RVOT gradient progression was also higher in the DPXG group than in the AG group (1.80 ± 0.06 vs 1.39 ± 0.04 mmHg/year, P < 0.001). There was no difference in freedom from RVOT graft dysfunction by 8 years when using AG and DPXG in adult Ross patients, nor in survival and freedom from RVOT conduit reintervention. Long-term results need further evaluation.


Epileptogenic activity induced by teicoplanin and effects of some antiepileptics in mice.
The present study was undertaken to clarify the epileptogenic activity induced by intracerebroventricular injection (i.c.v.) of methicillin-resistant Staphylococcus aureus (MRSA) antibiotics in mice. Teicoplanin (200 microg, i.c.v.) caused dose-related behavioral seizures such as head twitch and forelimb clonus. At the same time, the drug caused electroencephalographic (EEG) seizures characterized by spike-and-wave complex and a continuous spike with high amplitude. At a high dose (500 microg, i.c.v.), the drug caused a severe clonic convulsion followed by continuous spike and spike-and-wave complex on EEG. On the other hand, vancomycin caused no or almost no epileptogenic activity in both behavior and on EEG. Diazepam and sodium valproate dose-dependently antagonized epileptic seizures in behavior and on EEG induced by teicoplanin (500 microg, i.c.v.). In contrast, carbamazepine and ethosuximide caused no significant changes in both behavioral and EEG seizures induced by teicoplanin. From these findings, it can be concluded that teicoplanin may cause potent epileptogenic activity different from vancomycin when used clinically at extremely high doses. In addition, it may be that teicoplanin-induced seizure is closely related with the gamma-amino butyric acid (GABA)-ergic mechanism.