Breast cancer: why link early detection to reproductive health interventions in developing countries?
Breast cancer has not been sufficiently integrated into broader efforts either on maternal and child, or reproductive health and this presents an opportunity to strengthen early detection. The analysis is based on global breast cancer statistics and a bibliographic review of key global programs and strategies to promote women s health in the developing world. Breast cancer is a leading cause of cancer deaths in all regions of the developing world and is striking many women during the reproductive phase. There is an opportunity to increase awareness among women and undertake clinical examination to detect breast cancer by linking to existing health interventions related to reproductive and maternal and child health in developing countries. These synergies should be tested and evaluated in developing countries to identify the potential impact on early detection and on reducing the proportion of cases that are found in more advanced stages.


[Cardiac and plasma catecholamine response to dynamic exercise in hyperthyroidism].
To investigate cardiac and sympathoadrenal responses to dynamic exercise, heart rate, systolic blood pressure, serial plasma norepinephrine (NE) and epinephrine (E) concentrations during multistage treadmill exercise were measured in 24 hyperthyroid patients (mean age; 42 +/- 16) and 24 age-sex matched control subjects. Eleven patients were re-examined in the euthyroid state after antithyroid therapy. Exercise duration was shorter in patient with hyperthyroidism. Also, the heart rates and systolic blood pressures at rest and in the early stage of exercise were significantly higher in hyperthyroidism. NE at rest (normal vs hyperthyroid: 124 +/- 10 vs 80 +/- 7 pg/ml, p < 0.01) and NE at peak exercise (475 +/- 38 vs 310 +/- 38 pg/ml, p < 0.01) were lower in hyperthyroidism. E at rest (22 +/- 2 vs 29 +/- 4 pg/ml, n.s.) did not differ, however, E during the first stage of exercise (30 +/- 3 vs 69 +/- 12 pg/ml, p < 0.01) was higher in hyperthyroidism. Re-examination for the euthyroid state revealed the decreases in the heart rates and systolic blood pressures at rest and in the early stage of exercise, and the normalization of the NE and E response. Thus, patients with hyperthyroidism was in the hyperdynamic cardiac state at rest and during dynamic exercise, which was accounted for by decreased sympathetic nervous activity and increased adrenomedullary responses. These modifications of sympathoadrenal response seemed reversible when patients were controlled by antithyroid therapy.


Mechanism and Inhibitor Exploration with Binuclear Mg Ketol-Acid Reductoisomerase: Targeting the Biosynthetic Pathway of Branched-Chain Amino Acids.
Binuclear Mg ketol-acid reductoisomerase (KARI), which converts (S)-2-acetolactate into (R)-2,3-dihydroxyisovalerate, is responsible for the second step of the biosynthesis of branched-chain amino acids in plants and microorganisms and thus serves as a key inhibition target potentially without effects on mammals. Here, through the use of density functional calculations and a chemical model, the KARI-catalyzed reaction has been demonstrated to include the initial deprotonation of the substrate C2 hydroxy group, bridged by the two Mg ions, alkyl migration from the C2-alkoxide carbon atom to the C3-carbonyl carbon atom, and hydride transfer from a nicotinamide adenine dinucleotide phosphate [NAD(P)H] cofactor to C2. A dead-end mechanism with a hydride transferred to the C3 carbonyl group has been ruled out. The nucleophilicity (migratory aptitude) of the migrating carbon atom and the provision of additional negative charge to the di-Mg coordination sphere have significant effects on the steps of alkyl migration and hydride transfer, respectively. Other important mechanistic characteristics are also revealed. Inspired by the mechanism, an inhibitor (2-carboxylate-lactic acid) was designed and predicted by barrier analysis to be effective in inactivating KARI, hence probably enriching the antifungal and antibacterial library. Two types of slow substrate analogues (2-trihalomethyl acetolactic acids and 2-glutaryl lactic acid) were also found.


Characterization of marginal and Claudius' cells growing from cochlear explants in vitro.
Tissue specimens of stria vascularis together with spiral ligament were transferred from the guinea pig cochlea to tissue culture dishes. To characterize and identify cells growing out from the explants, indirect immunofluorescence microscopy was used. The expression of the intermediate-sized filaments vimentin and cytokeratin 18 in cells on the surface of tissue specimens and in cells growing out from the explants after different cultivation periods were compared. Basically, three types of cells grew from the explants during several days: marginal cells, Claudius' cells and fibroblast-like cells. In primary cultures of explants, growth of marginal cells was observed in 25% of the dishes. Their proliferative activity, estimated by the use of the BrdUrd-DNA antibody, started in the stria vascularis and continued across the attachment of Reissner's membrane down to the bottom of the cell culture dish. The newly-formed marginal cells expressed cytokeratin 18 in the same way that original marginal cells on the tissue specimen do. If the newly-formed marginal cells were in contact with fibroblast-like cells or were forming groups (domes) on the bottom, they expressed vimentin. In 3% of the dishes growth of Claudius' cells was observed. Proliferative activity of these cells was found at the point where the basilar membrane was attached to the spiral ligament. New Claudius' cells spread at the opposite side of an explant when compared with the location of new marginal cells. Original as well as newly-formed Claudius' cells contained cytokeratin 18. Fibroblast-like cells were commonly present in cultures and contained only vimentin.


Downregulation of RUVBL1 inhibits proliferation of lung adenocarcinoma cells by G1/S phase cell cycle arrest via multiple mechanisms.
Lung cancer remains a leading cause of cancer-related mortality and morbidity worldwide, of which non-small cell lung cancer (NSCLC) accounts for 80 %. RUVBL1 is a highly conserved eukaryotic AAA+ adenosine 5'-triphosphatase (ATPase) that has many functions highly relevant to cancer. We therefore attempted to determine the potential role of RUVBL1 in the biogenesis of lung adenocarcinoma and obtained some interesting results. Our study revealed that RUVBL1 expression was higher in lung adenocarcinoma specimens than in those of adjacent non-tumor tissues and in lung cancer cell lines than in normal lung cell lines. RUVBL1 knockdown via siRNA reduced proliferation and caused G1/S phase cell cycle arrest in lung adenocarcinoma cell lines. The G1/S phase cell cycle arrest triggered by RUVBL1 downregulation could be attributed, at least in part, to repression of the AKT/GSK-3β/cyclin D1 pathway and probably to the activation of IRE1α-mediated endoplasmic reticulum (ER) stress. We thus demonstrated for the first time that a knockdown of RUVBL1 could effectively inhibit the proliferation of lung adenocarcinoma A549 and H292 cells through the induction of G1/S phase cell cycle arrest via multiple mechanisms. These observations strongly suggested that RUVBL1 should be considered a promising target for the prevention or therapy of lung adenocarcinoma.


Self assembled ionically sodium alginate cross-linked amphotericin B encapsulated glycol chitosan stearate nanoparticles: applicability in better chemotherapy and non-toxic delivery in visceral leishmaniasis.
To investigate the applicability, localization, biodistribution and toxicity of self assembled ionically sodium alginate cross-linked AmB loaded glycol chitosan stearate nanoparticles for effective management of visceral leishmaniasis. Here, we fabricated Amphotericin B (AmB) encapsulated sodium alginate-glycol chitosan stearate nanoparticles (AmB-SA-GCS-NP) using strong electrostatic interaction between oppositely charged polymer and copolymer by ionotropic complexation method. The tagged FAmB-SA-GCS-NP was compared with tagged FAmB for in vitro macrophagic uptake in J774A macrophages and in vivo localization in liver, spleen, lung and kidney tissues. The AmB-SA-GCS-NP and plain AmB were compared for in vitro and in vivo antileishmanial activity, pharmacokinetics, organ distribution and toxicity profiling. The morphology of SA-GCS-NP revealed as nanocrystal (size, 196.3 ± 17.2 nm; PDI, 0.216 ± 0.078; zeta potential, (-) 32.4 ± 5.1 mV) by field emission scanning electron microscopy and high resolution transmission electron microscopy. The macrophage uptake and in vivo tissue localization studies shows tagged FAmB-SA-GCS-NP has significantly higher (~1.7) uptake compared to tagged FAmB. The biodistribution study of AmB-SA-GCS-NP showed more localized distribution towards Leishmania infected organs i.e. spleen and liver while lesser towards kidney. The in vitro (IC50, 0.128 ± 0.024 μg AmB/ml) and in vivo (parasite inhibition, 70.21 ± 3.46%) results of AmB-SA-GCS-NP illustrated significantly higher (P < 0.05) efficacy over plain AmB. The monomeric form of AmB within SA-GCS-NP, observed by UV-visible spectroscopy, favored very less in vitro and in vivo toxicities compared to plain AmB. The molecular organization, toxicity studies, desired localization and biodistribution of cost effective AmB-SA-GCS-NP was found to be highly effective and can be proved as practical delivery platform for better management of leishmaniasis.


Cardiothoracic surgery training in Israel: A critical look at the past, aiming for a better future.
Training the next generation of cardiothoracic surgeons is a global persistent challenge. Major issues, including length of training, decreasing volume of cases, shift toward high-risk, complex, and less-invasive procedures, increased specialization, and uncertainty with regard to future employment, are relevant and affect residency training programs in the United States, Europe, and other parts of the world. To produce high-quality, mature, and qualified surgeons, these challenges mandate an ongoing effort by our specialty leadership aimed at identifying creative solutions and adapting the current residency training curricula and methodology to the dynamic changes in our field. The current situation in Israel is discussed with the hope that sharing our experience might be useful and lead to adoption of some of our solutions by other countries.


Prevalence of diabetes and dyslipidemia in hypertensive patients in the area of Blida (Algeria).
Diabetes mellitus (DM) and lipid disorders (LD) in hypertensive patients are associated with an increased risk of cardiovascular complications requiring follow-up and more aggressive therapeutic strategies. The main objective of this study was to describe the prevalence of DM and LD in adult hypertensive patients followed in specialized consultation of hypertension in the region of Blida (North Algeria) during the period from January 2013 to June 2017. We included 3268 hypertensive patients (1453 men and 1815 women), mean age of 58.3±13.8years. Descriptive statistics were used to estimate means by sex and age for subgroups [under 30, 30-39, 40-49, 50-60, over 70]. A linear regression was used to determine annual trends. The age and sex specific results were adjusted to the general population data of the city of Blida for a period of 4years and each year studied. The mean prevalence of diabetes was 21.8% and glucose tolerance was 10.9% without significant trend of increase during the study period in the overall population and according to sex, while in the subgroup of hypertensive patients over 60, there has been an increase in the prevalence of diabetes and a decrease in glucose tolerance over the 4 years (R2=0.78, P=0.05 and R2=0.95, P=0.005, respectively). The mean prevalence of LD for the study period was 16.1% without significant trend at 4years. The increase in total cholesterol combined with the increase in low-density lipoprotein (LDL) levels was the most common disorder (32.2%). There was no significant difference in LD prevalence and characteristics in subgroups by sex. Age group analysis showed a greater increase in the frequency of lipid disorders in patients over 60years of age (R2=0.80, P=0.001). Over the 4years of study, age over 60 was associated with an increase in the prevalence of metabolic disorders in hypertensive patients. This trend may explain the poor control of BP. Above all, it must be taken into account for the requirement to achieve therapeutic objectives that effectively reduce the risk of cardiovascular complications occurring in these high-risk patients whose number is becoming increasingly important.


[Effect of ethyl ether of p-chlorphenoxyisobutyric acid on the glucocorticoid function of the adrenal cortex of guinea pigs].
In administration to quinea pigs of ethyl-p-chlorophenoxyisobutyrate daily in a dose of 0.2 g/kg per os for 15-26 days decreased the 17-OHCS concentration in the peripheral blood plasma. A fall of the urinary excretion of individual 17-OHCS occurred chiefly at the expense of free unchanged cortisol, tetrahydrocortisol and tetrahydro-11-desoxycortisol. The zona fasciculate displays the abundance of the sudanophilic material. A test with ACTH demonstrated that the present functional reserves of the adrenal cortex failed to change under the effect of the preparation. The content of NEFA decreased in the blood serum; as to cholesterol level - it reamined unchanged. Possible mechanisms of the action of the preparation and prospects of its use for the treatment of hypercorticism are discussed.


The use of rhodamine 6G and fluorescence microscopy in the evaluation of phospholipid-based polymeric biomaterials.
A technique is described that allows the staining and subsequent visualization of polymers that contain the phosphorylcholine (PC) group. These materials are useful as bulk materials or coatings for the fabrication of medical devices. The staining method employs rhodamine 6G, which can be simply and rapidly applied to the polymer coating and imaged using fluorescence microscopy. The specificity of the staining for the PC polymers makes this technique suitable for the evaluation of a wide range of substrates and provides qualitative information on coating uniformity, coverage and morphology. It can be used to examine the durability of, and defects in, the coating. Statistical analysis of the fluorescent intensity by measuring the pixel value during imaging can allow for the method to be used as a quality control tool.


The role of interpreters in inclusive classrooms.
The roles of interpreters in an inclusive classroom were examined through a qualitative, 3-year case study of three interpreters in an inclusive school. Interviews were conducted with interpreters, classroom teachers, special education teachers, and administrators. The interview data were supplemented with observations and field notes. Results indicate that in addition to sign interpreting between American Sign Language and speech, the interpreters clarified teacher directions, facilitated peer interaction, tutored the deaf children, and kept the teachers and special educators informed of the deaf children's progress. The interpreter/aides and the classroom teachers preferred this full-participant interpreter role, while the special educators and administrators preferred a translator role. Classroom teachers were more comfortable with full-time interpreters who knew the classroom routine, while the special educators and administrators feared that full-time interpreters fostered child and teacher dependence. These issues are discussed in terms of congruence with the Registry of Interpreters code of ethics and how integration of young children might be best facilitated.


Analysis of laser-induced fluorescence spectra of in vitro plant tissue cultures.
We demonstrate the effectiveness of laser-induced fluorescence (LIF) for monitoring the development and stress detection of in vitro tissue cultures in a nondestructive and noninvasive way. The changes in LIF spectra caused by the induction of organogenesis, the increase of the F690/F740 ratio as a result of the stress originated in the organogenic explants due to shoot emergence, and the relationship between fluorescence spectra and shoot development were detected by LIF through closed containers of Saintpaulia ionantha.


Increase in epsilon(gamma-glutamyl)lysine crosslinks in atherosclerotic aortas.
Portions of aortas from normal and atherosclerotic rabbits and from human autopsy subjects were washed and separated into layers which were subjected to exhaustive proteolytic digestion. The digests were assayed for epsilon(gamma-glutamyl)lysine crosslinks by a two-stage high performance liquid chromatography (HPLC) procedure. Crosslink concentrations in intima-media from rabbits where more than 15% of the aorta lumen surface was lesioned are greater than in normal aortas or aortas with less than 15% of the surface lesioned. Higher crosslink concentrations occur in fibrolipid plaques from human aortas than in intima-media layers of equal thickness from non-lesioned areas of the same aortas. Much of the crosslink in fibrolipid plaques occurs in the proteins which float at d < 1.18 g/ml. Non-lesioned areas of intima-media from aortas with fatty streaks or plaques have higher crosslink concentrations than intima-media from aortas with no lesions. In normal and lesioned intimas thinner than 0.2 mm, the concentration of the crosslink is lower than in the subjacent media. These findings indicate that increased epsilon(gamma-glutamyl)lysine crosslinking occurs in the atherosclerotic aorta and is associated principally with smooth muscle cells. It is suggested that the crosslinked products may be involved in retention of lipoproteins and the increase in collagen production.


[Identification of Rostellularia procumbens (L.) Nees].
To identify the commonly used Chinese traditional herb Rostellularia procumbens (L.) Nees. The appearance, morphological features and microscopic characteristics were adopted to identify Rostellularia procumbens (L.) Nees. Rostellularia procumbens (L.) Nees is an annual herb with typical spike, but without involucre bracts under inflorescence. The corolla appears 2 labiate lips and 2 stamens. The capsularfruit consists of 4 seeds. The stems of the herbs are six-ribbed and cylindrical with the lavender node.The oblong leaves with full margin are wrinkled and bent.The herbs are tasteless. The pollen grains is long-oval shaped with 2-colposate, and the pollen exine presents with concentrated echinate sculpture. Stomata is diacytic type with non-glandular hairs, and mostly consists of 3-5 cells. Glandular scales are more common and composed of 4 cells with intumescent and oblate head. There are numerous long-elliptical or clavate calcium carbonate crystals (cystolith) in the stems and leaves, with papillary protruding. The appearance, morphological features and microscopic characteristics can be used for the quality identification of Rostellularia procumbens (L.) Nees.


Multiple-wave lateral shearing interferometry for wave-front sensing.
Multiple-wave achromatic interferometric techniques are used to measure, with high accuracy and high transverse resolution, wave fronts of polychromatic light sources. The wave fronts to be measured are replicated by a diffraction grating into several copies interfering together, leading to an interference pattern. A CCD detector located in the vicinity of the grating records this interference pattern. Some of these wave-front sensors are able to resolve wave-front spatial frequencies 3 to 4 times higher than a conventional Shack-Hartmann technique using an equivalent CCD detector. Its dynamic is also much higher, 2 to 3 orders of magnitude.


The Basic Empathy Scale: Factor structure and validity in a sample of inpatient adolescents.
The Basic Empathy Scale (BES) is used widely to measure empathy in adolescents. Despite this wide use, there has been no examination of the measure's factor structure or its validity in an American or severe clinical sample. The present study addressed this gap by evaluating factor structure and construct validity in an inpatient sample of 652 adolescents (63% female). Results indicated that a bifactor model, with a general empathy factor and specific factors of affective and cognitive processes, provided the best fit of the data. After examining factor loadings for both the general and specific factors and calculating model-based reliability estimates, we conclude that the two specific factors represent measurement-specific error due to wording and the confounding construct of emotion recognition, respectively, and that BES total scores should be used in scoring and interpretation to capture the construct of empathy. BES total scores were positively associated with prosocial behavior, negatively associated with affective components of psychopathy (unemotionality, callousness, and uncaringness), and significantly higher for girls than for boys further bolstering the conclusion that the BES total score is a valid measure of empathy in adolescents with severe psychopathology. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Clostridium sulfidigenes sp. nov., a mesophilic, proteolytic, thiosulfate- and sulfur-reducing bacterium isolated from pond sediment.
A novel strictly anaerobic, endospore-forming, rod-shaped, Gram-positive bacterium, designated strain SGB2(T), was isolated from a mixed culture from a pond sediment during screening for sulfate-reducing bacteria capable of degrading cyanophycin (CGP). In this study, the taxonomic characterization of this mesophilic, proteolytic Clostridium isolate and the role which it, and its phylogenetic relatives, may play in peptide degradation and in the sulfur cycle are reported. Strain SGB2(T) was a commensal strain, utilizing CGP degradation products produced by other micro-organisms. Cells were motile until sporulation, forming oval, terminal spores that swell the cells. It showed optimum growth at 34 degrees C, pH 6.6 and in the absence of NaCl. Strain SGB2(T) utilized proteinaceous compounds such as peptone, Casamino acids, gelatin and trypticase soy, in addition to several amino acids and pyruvate. Utilization of many of these compounds was enhanced in the presence of thiosulfate. The isolate was unable to use any of the carbohydrates or alcohols investigated or CGP as carbon and energy sources. Thiosulfate and elemental sulfur were used as terminal electron acceptors. Phylogenetic analysis revealed that strain SGB2(T) belongs to the low-G+C-containing Clostridiales group. It exhibited 99 % 16S rRNA gene sequence similarity to its closest relatives Clostridium thiosulfatireducens Lup21(T) and Clostridium subterminale DSM 6970(T). DNA-DNA hybridization values with these two strains were 39.4 and 42.1 %, respectively. Based on phenotypic, genotypic and phylogenetic characteristics, we conclude that the isolate represents a novel species of the genus Clostridium, Clostridium sulfidigenes sp. nov. The type strain is SGB2(T) (=DSM 18982(T) =ATCC BAA-1538(T)).


Theory and experimental method for determining individual kinetic constants of fast-acting, irreversible proteinase inhibitors.
A theory and experimental method are presented to characterize the kinetics of fast-acting, irreversible proteinase inhibitors. The theory is based upon formal analysis of the case of an irreversible inhibitor competing with a substrate for the active-site of a proteinase. From this theory, an experimental method is described by which the individual microscopic kinetic constants for the interaction of the inhibitor with the proteinase can be determined. These are, for a two-step inhibition reaction sequence, the equilibrium dissociation constant and the first-order rate constant for inhibition, and, for a one-step inhibition reaction sequence, the second-order rate constant for inhibition. The theory and experimental method were validated by an analysis of the inhibition of trypsin by the two-step synthetic inhibitor p-nitrophenyl p-guanidinobenzoate and the one-step protein inhibitor bovine pancreatic trypsin inhibitor. The substrate used in these experiments is a new, fluorogenic substrate for trypsin-like serine proteinases (Cbz-Ile-Pro-Arg-NH)2-Rhodamine, the synthesis and properties of which are described.


A technique for the measurement of patellar tracking during weight-bearing activities using ultrasound.
A new fixation device, the femoral clamp, was developed in this study for the ultrasound measurement of patellar medio-lateral motion during sitting and squatting knee flexion/extension. Seventeen subjects, 6 males, 11 females, aged between 18 and 40 years were recruited for the test. Results showed that the patella moved medially then laterally from extension to flexion when sitting. Weight-bearing knee motion produced a more laterally tracked patella without the presence of the initial medial patellar translation. The tracking patterns of the patellae were similar regardless of knee movement direction. The patellar lateral position was greatly affected by the movement task (p < 0.0005), and was also influenced by gender for maximum medial position (p < 0.05). The reproducibility of the measurement was between 0.29 and 0.90 for the intra-rater and 0.34-0.75 for the inter-rater reliability. The accuracy of the ultrasound measurement was validated by interventional magnetic resonance (iMR) imaging of the patella and the mean error of the measurement was 1.4 +/- 3.2 mm. Although further research is needed to improve the accuracy and reliability of this method, it has demonstrated the feasibility of obtaining patellar tracking data during load-bearing activities.


Cross-species chromosome painting in Cetartiodactyla: reconstructing the karyotype evolution in key phylogenetic lineages.
Recent molecular and morphological studies place Artiodactyla and Cetacea into the order Cetartiodactyla. Within the Cetartiodactyla such families as Bovidae, Cervidae, and Suidae are well studied by comparative chromosome painting, but many taxa that are crucial for understanding cetartiodactyl phylogeny remain poorly studied. Here we present the genome-wide comparative maps of five cetartiodactyl species obtained by chromosome painting with human and dromedary paint probes from four taxa: Cetacea, Hippopotamidae, Giraffidae, and Moschidae. This is the first molecular cytogenetic report on pilot whale, hippopotamus, okapi, and Siberian musk deer. Our results, when integrated with previously published comparative chromosome maps allow us to reconstruct the evolutionary pathway and rates of chromosomal rearrangements in Cetartiodactyla. We hypothesize that the putative cetartiodactyl ancestral karyotype (CAK) contained 25-26 pairs of autosomes, 2n = 52-54, and that the association of human chromosomes 8/9 could be a cytogenetic signature that unites non-camelid cetartiodactyls. There are no unambiguous cytogenetic landmarks that unite Hippopotamidae and Cetacea. If we superimpose chromosome rearrangements on the supertree generated by Price and colleagues, several homoplasy events are needed to explain cetartiodactyl karyotype evolution. Our results apparently favour a model of non-random breakpoints in chromosome evolution. Cetariodactyl karyotype evolution is characterized by alternating periods of low and fast rates in various lineages. The highest rates are found in Suina (Suidae+Tayasuidae) lineage (1.76 rearrangements per million years (R/My)) and the lowest in Cetaceans (0.07 R/My). Our study demonstrates that the combined use of human and camel paints is highly informative for revealing evolutionary karyotypic rearrangements among cetartiodactyl species.


[Tool and procedures for research in psychiatric nursing. II - Inventory of possible situations in psychiatric nursing].
The author lists situations in which psychiatric patients' basic needs are affected and possible activities of the nursing personnel to meet them.


Evaluation of environmental compatibility of EAFD using different leaching standards.
A study on laboratory scale to evaluate the environmental compatibility of electric arc furnace dust (EAFD) is reported in this article. EAFD, a waste by-product of the steel-making process, was generated on a steel plant located in Brazil. Different leaching tests, NBR10005 (Brazilian), AFNORX31-210 (French), JST-13 (Japanese), DIN38414-S4 (German), TCLP (American), and NEN 7343 (Netherland) were conducted. These leaching procedures are batch tests and are columns conducted in a way that an equilibrium condition should be achieved. The pH of the medium showed a crucial parameter governing the release of metals from the solid phase into solution. As the pH of the medium varies with the leachant used, this determines the dissolution of the elements. Zn, Pb, Mn, Cd, and Cu presented high leachability at NBR10005 procedures (acid pH). Except Pb and Cr, the leachability of all others metals in leaching tests with alkaline pH decreases with the increase of the pH. NBR10005 classifies the EAFD as a hazardous waste due to high concentration of Pb and Cd in leachate. The column tests are presented in the following order of leaching: Pb>Cr>Zn>Mn>Cu>Cd.


Nuclear 3,5,3'-triiodothyronine (T3) in brown adipose tissue: receptor occupancy and sources of T3 as determined by in vivo techniques.
The amount and sources of T3 associated with high affinity, low capacity cellular nuclear receptors in brown adipose tissue (BAT) have been estimated by in vivo pulse-labeling techniques. Maximal binding capacity was measured by in vivo saturation analysis. Nuclear receptor occupancy at endogenous levels of T3 and T4 in euthyroid rats was estimated from the equilibrium nuclear to serum ratio of tracer T3, and the locally generated nuclear T3 to serum T4 ratio after injecting tracer T3 and T4. These ratios were multiplied, respectively, by the endogenous concentrations of T3 and T4 as measured by RIA. The maximal binding capacity was 0.65 ng T3/mg DNA, and saturation was 71%. Fifty-five percent of the nuclear T3 was generated locally, and 45% was derived from circulating T3. BAT is, hence, comparable to the liver in number of receptors (approximately 5000/cell) and to the pituitary with regard to saturation and relative contributions of locally generated T3 and plasma T3 to nuclear T3. These results suggest that BAT may be an important target for thyroid hormones and, along with other data, that alterations in the activity of the type II 5'-deiodinase of this tissue may influence the saturation of nuclear T3 receptors.


Effect of weekly high-dose vitamin D3 supplementation on serum cholecalciferol concentrations in pregnant women.
Vitamin D status is conventionally defined by the serum concentration of 25-hydroxyvitamin D. However, it has been proposed that the serum cholecalciferol concentration (D3) also determines functional vitamin D sufficiency. The objective of this study was to describe the effect of weekly high-dose vitamin D3 supplementation on inter-dose serum D3 in pregnant women. We conducted a sub-study of a completed randomized double-blind placebo-controlled trial of vitamin D3 (35,000 IU/week) supplementation in late pregnancy (AViDD trial) in Dhaka, Bangladesh. This study included pregnant women enrolled at 26-29 weeks gestation who fully adhered to the prenatal supplement intervention for ≥8 consecutive weeks and for whom serum samples were available for D3 analysis (n=65). Serum D3 was uniformly low at enrolment. Mean D3 increased and was maximal at 1 day after vitamin D dose administration (152.09nmol/L, SD 25.11nmol/L) and remained significantly higher in VitD vs. Pl at 7 days (29.59nmol/L vs. 1.92nmol/L, p=0.007). Daily average of the group mean D3 during the week following dosing was 66.97nmol/L in VitD versus 2.13nmol/L in Pl. In conclusion, serum D3 remained significantly elevated throughout the week following ≥8 consecutive weekly doses of 35,000 IU D3 in pregnant women. However, the clinically significant minimum threshold of serum D3 remains to be established.


Accumulation of mutations in reverse transcriptase of hepatitis B virus is associated with liver disease severity in treatment-naïve Chinese patients with chronic hepatitis B.
Mutations in reverse transcriptase (RT) of the hepatitis B virus (HBV) are demonstrated to be strongly associated with nucleos(t)ide analog resistance, which is supposed to be the biggest obstacle during the long-term anti-viral treatment of chronic hepatitis B. However, the presence of RT mutations in treatment-naïve chronic hepatitis B patients and its clinical significance are not well known. To investigate the significance of mutations in reverse transcriptase of the hepatitis B virus in treatment-naïve Chinese patients with chronic hepatitis B. In this study, 288 treatment-naïve chronic HBV patients were recruited and the RT region was sequenced. The results showed that 71 patients (24.65%) were found with RT mutations, within which there were no well-defined primary nucleotide analog-resistant mutations. There were a total of 28 mutant sites, which formed three dominant mutant clusters: rt124-139, rt191-212 and rt225-229. Among these 71 patients, 63.38% (45/71) of patients had a single mutation while 19.72% (14/71), 12.68% (9/71) and 4.23% (3/71) of patients had 2, 3 or 4 mutations, respectively. Patients with RT mutations showed significantly decreased serum baseline HBV DNA loads (p = 0.0363) and blood platelet count (p = 0.0181) than patients without RT mutations. Patients with multiple mutant sites (≥ 2) had significantly decreased baseline HBV DNA loads (p = 0.0004) and blood platelet count (p = 0.0011) than patients with single mutant site. Moreover, the number of RT mutant sites is significantly associated with severity of liver fibrosis (p = 0.0128). This study demonstrated that there was a prevalence of RT mutations in treatment-naïve chronic hepatitis B patients, which reflects a tougher liver environment for the virus and deeper liver injury for the host. Accumulation of RT mutations was associated with liver disease severity in treatment-naïve chronic hepatitis B patients.


Sacred content, secular context: a generative theory of religion and spirituality for social work.
Although a secular profession, social work practitioners and educators do explore human spirituality, and this is embraced now by the profession as integral to a holistic view of the human being. Social workers in hospice and end-of-life care are on the front line of this shift. Still needed is for the profession to coalesce around a generative theory of religion to inform the discipline. The author proposes that a synthesis of ideas, particularly from anthropologists Ernest Becker and Fredrick Streng, provides a generative theory of religion that advances meaningful interface between diverse religious and spiritual ideations of clients and clinicians alike. This theory of generative death anxiety locates the basic religious urge as response to the human awareness of the ontological condition of mortality, which then becomes expressed existentially in all of its diverse particularities. This approach avoids being overly reductionist, yet does provide categories for clear analysis. It cultivates critical respect for human religiosity and fosters productive and creative incorporation of human spirituality into the practical and pragmatic clinical perspective.


The physical properties of packable and conventional posterior resin-based composites: a comparison.
The authors compared the physical properties of three packable hybrid resin-based composites with those of a conventional hybrid and a microfill composite material advocated for use as posterior restorative materials. They evaluated diametral tensile strength, or DTS; compressive strength, or CS; flexural strength, or FS; and depth of cure, or DC. The authors studied the following resin-based restorative materials: three packable composites, Alert Condensable Composite (Jeneric Pentron), SureFil High Density Posterior Restorative (Dentsply Caulk) and Solitaire (Heraeus Kulzer); one conventional hybrid composite, TPH Spectrum (Dentsply Caulk); and one microfill, Heliomolar Radiopaque (Ivoclar-Vivadent). The authors evaluated DTS, CS, FS and DC, according to American National Standards Institute criteria. They made scanning electron micrographs of the packable resin-based composites. Results demonstrated that the conventional hybrid, TPH Spectrum, had significantly greater DTS and FS than other resin-based composites. Alert and SureFil had comparable DTS and FS, which were significantly greater than Heliomolar's DTS and FS. Solitaire had significantly lower DTS and FS than all other resin-based composites. SureFil had the highest CS, followed by TPH Spectrum, Solitaire and Alert, which were comparable and had significantly greater CS than Heliomolar. TPH Spectrum and Alert had significantly greater DC than all other resin-based composites, followed in decreasing order by SureFil, Solitaire and Heliomolar. While the packable composites tested in this study had physical properties superior to those of the microfill composite, they were no better suited for use as a posterior restorative material than was the conventional hybrid resin-based composite. Packable composites may be easier for clinicians to handle than conventional resin-based composites; however, their physical properties were not superior to those of the conventional small-particle hybrid resin-based composite. In addition, these materials may have the clinical drawback of increased wear and surface roughness that was seen with early, large-particle composite restorative materials.


High-dose cefazolin on consecutive hemodialysis in anuric patients with Staphylococcal bacteremia.
Methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia is a leading cause of infection in hemodialysis (HD) patients. Cloxacillin, cefazolin, and vancomycin are the mainstay antimicrobials. Cloxacillin administration leads to frequent drug dosing, longer length of stay (LOS), and higher cost, while resistance and poorer outcomes are associated with vancomycin use. Dosing cefazolin during HD allows for prolonged blood therapeutic levels. We assessed the outcomes and safety of a strategy of treating MSSA bacteremia with 2-3 g cefazolin on HD only. All HD patients with MSSA bacteremia admitted in June-December 2009 at our center and receiving this regime were compared with historical controls who received cloxacillin. Demographic characteristics and outcome measures like mortality, LOS, cost, recrudescence, and adverse drug reactions were assessed. Of 27 consecutive episodes reviewed, 14 and 13 patients received cefazolin and cloxacillin, respectively. Baseline demographics were comparable between the 2 treatment groups. More than one-third of the bacteremia was related to tunneled catheter infection. The 30-day mortality of cloxacillin- and cefazolin-treated patients was 15% and 7%, respectively (P=0.14). Two of the 11 survivors treated with cloxacillin (18%) had recrudescent bacteremia while none was observed in cefazolin-treated survivors. Cefazolin was associated with shorter LOS (10 vs. 20 days, P<0.05) and lower cost (US$8262.00 vs. US$15,367.00, P<0.05). Cefazolin use resulted in 3 idiosyncratic adverse drug reactions. Cefazolin dosed on each HD in MSSA bacteremia leads to earlier discharge and less cost. Larger prospective studies are, however, warranted to fully assess its safety and efficacy.


Biomimetic optimisation of branched fibre-reinforced composites in engineering by detailed analyses of biological concept generators.
The aim of this study is the biomimetic optimisation of branched fibre-reinforced composites based on the detailed analysis of biological concept generators. The methods include analyses of the functional morphology and biomechanics of arborescent monocotyledons and columnar cacti as well as measurements and modelling of mechanical properties of biomimetic fibre-reinforced composites. The key results show evidence of notch stress reduction by optimised stem-branch-attachment morphology in monocotyledons and columnar cacti. It could be shown that some of these highly interesting properties can be transferred into biomimetic fibre-reinforced composites.


[Clinical significance of interaction between Chlamydia infection (Chlamydia pneumoniae) and free radical processes during ischemic heart disease].
To determine occurrence and activity of chlamydial infection (CI) as well as activity of free radical processes in clinical course of different forms of ischemic heart disease. 34 coronary heart disease (CHD) patients entered the study. 23(67.6%) of them had effort angina and unstable angina, 11(32.4%) patients had non-Q myocardial infarction (19 men and 15 women). 14 healthy donors served control. CI was detected with enzyme immunoassay. The examinations were made in exacerbation and 2 weeks later in clinical improvement. Chlamydia pneumoniae infection in the tissues of the aorta and left coronary artery was studied in 15 dead bodies using the polymeric chain reaction. Generation of active oxygen forms by leukocytes was tested by luminol-dependent chemiluminescence method. In addition, the patients and donors were examined for malonic dialdehyde. Titers of IgA and IgG of C. pneumoniae antibodies were high in CHD exacerbation. IgM antibodies were not found in the diagnostic titers. Follow-up values of IgA and IgG titers lowered. C. pneumoniae was found in 12 of 15 autopsy specimens. Basal and stimulated indices of leukocytic generation of active oxygen forms in patients with CHD exacerbation were higher than in donors. Later, the generation declined. Malonic dialdehyde was also elevated in the exacerbation and lowered in clinical improvement. A correlation exists between IgA and IgG antibodies titers and chemiluminescence intensity in CHD exacerbation. In progression of atherosclerotic process including CHD and its exacerbations CI and free radical processes activate. These may be related showing a feasibility of C. pneumoniae involvement in development of atherosclerosis.


Development of the cytodetachment technique to quantify mechanical adhesiveness of the single cell.
Adhesion of cells to biomaterials or to components of the extracellular matrix is fundamental in many tissue engineering and biotechnological processes, as well as in normal development and tissue maintenance. Many cells on adhesive molecules will spread and form an organized actin cytoskeleton and complex transmembrane signaling regions called focal adhesions. Focal adhesions appear to function as both signaling and stabilizing components of normal adherent cell activity. To better understand adhesion formations between cells and their underlying substrata, we have designed, developed, and utilized a novel 'cytodetachment' methodology to quantify the force required to displace attached cells. We allowed bovine articular chondrocytes to attach and spread on a substratum of either fibronectin, bovine serum albumin, or standard microscope glass. The cytodetacher was then employed to displace the cells from the substratum. Our results demonstrate that a significantly greater force is required to detach cells from fibronectin versus the two other substrata, suggesting that a cell's actin cytoskeleton and perhaps focal adhesions contribute significantly to its mechanical adhesiveness. The cytodetacher allows us to directly measure the force required for cell detachment from a substratum and to indirectly determine the ability of different substrata to support cell adhesion.


Globoid cell leukodystrophy (Krabbe disease): normal umbilical cord blood galactocerebrosidase activity and polymorphic mutations.
Globoid cell leukodystrophy is an inherited metabolic disorder of the central nervous system caused by deficiency of the lysosomal enzyme galactocerebrosidase. Haematopoietic stem cell transplantation is the only available effective treatment. The engraftment from normal donors provides competent cells able to correct the metabolic defect. Umbilical cord blood cells have proved to significantly decrease complications and improve engraftment rate compared to adult marrow cells in haematopoietic stem cell transplantation. Umbilical cord blood cells must be of sufficient activity to provide central nervous system recovery after engraftment is obtained. Galactocerebrosidase activity is known to be affected by two polymorphic alleles found at nucleotides 502 and 1637 of the cDNA for this gene. This enzyme activity and the polymorphic alleles noted above were analysed in 83 random samples of umbilical cord blood. The activity, assayed with the fluorogenic substrate 6-hexadecanoylamino-4-methylumbelliferyl-beta-galactopyranoside, in those with neither polymorphic allele was 4.6 +/- 1.7 units (nmol/h per mg protein). This optimal choice of cord blood was found in only 24% of specimens. Homozygotes for 1637T > C with activity of only 1.5 +/- 0.4 units represented 16% of the samples. Those heterozygous for 1637T > C with slightly better activity (2.3 +/- 0.7 units) represented 52% of the samples. Choice of umbilical cord blood for haematopoietic stem cell transplantation, therefore, requires consideration not only of cell quantity and HLA compatibility but also selection for normal alleles to obtain maximal enzymatic activity for central nervous system correction.


Mercury and other elements in lichens near the INA Naftaplin gas treatment plant, Molve, Croatia.
This paper describes the use of epiphytic lichens as bioindicators for spatial monitoring of mercury and other elements in air near the natural gas treatment facilities at Molve, Croatia. It is well known that at this location the concentration of mercury in natural gas is very high and therefore it has to be removed from natural gas before further processing in order to prevent technological and environmental problems. In order to monitor the efficiency of an industrial facility for removal of mercury from natural gas, mercury measurements in air and lichens were performed during 9 months in 1997/1998. In situ lichens Parmelia sulcata, Xantoria parientina and Hypogymnia physodes and transplanted lichen species Hypogymnia physodes were used. A good correlation between mercury concentrations in air and lichens was found. The concentrations of barium and bromium were also significantly elevated in transplanted lichens, most probably related to technological process at the gas treatment plant and/or other geological factors. It was confirmed that lichens can successfully be used as bioindicators, provided a careful experiment is designed, particularly the amount of lichens transplanted, the duration of exposure and the initial levels and homogeneity of transplanted lichens.


Evaluation of 18F-BCPP-EF for mitochondrial complex 1 imaging in the brain of conscious monkeys using PET.
We have reported on the development of a novel PET probe, (18)F-2-tert-butyl-4-chloro-5-{6-[2-(2-fluoroethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one ((18)F-BCPP-EF), for quantitative imaging of mitochondrial complex 1 (MC-1) activity in the brain of the living rat. For clinical application in humans, translational research in the monkey was conducted. PET measurements with (18)F-BCPP-EF were performed in young and old monkeys (Macaca mulatta) in a conscious state with arterial blood sampling. The binding specificity of (18)F-BCPP-EF was evaluated with rotenone, a specific MC-1 inhibitor, in young animals. The binding (total distribution volume, V T) of (18)F-BCPP-EF was calculated using Logan graphical analysis, and one-tissue compartment model (1-TC) and two-tissue compartment model (2-TC) analyses using a metabolite-corrected plasma input function. F-BCPP-EF was rapidly taken up into the brain just after intravenous injection, peaked between 10 and 20 min after injection, and was then gradually eliminated. The 2-TC analysis provided a better fit than the 1-TC analysis, and the V T values from the 2-TC analysis correlated well with those from the Logan plot. With predosing with rotenone, (18)F-BCPP-EF showed a higher uptake peak in the brain, followed by more rapid elimination thereafter than in the vehicle condition, resulting in significant reductions in 2-TC V T values in all regions. In old animals, the kinetics of (18)F-BCPP-EF were slightly slower with lower peak levels than in young animals, resulting age-related reductions in (18)F-BCPP-EF binding in all brain regions. The present study demonstrated that (18)F-BCPP-EF may be a potential PET probe for quantitative imaging MC-1 activity in the living brain using PET.


Advances in the medical therapy of inflammatory bowel disease.
The medical therapy of inflammatory bowel disease (IBD) has advanced significantly over the past year. Serologic markers of IBD have been further investigated and better defined, showing some discriminatory power with potential therapeutic implications. Studies of azathioprine and 6-mercaptopurine metabolites will make it easier and safer to use these effective drugs. Clinical data using other immunomodulators, including 6-thioguanine, mycophenolate mofetil, cyclosporine, and tacrolimus, continue to accrue with positive results. Infliximab has become even more firmly established as a reliable and effective therapy for active and fistulizing Crohn disease and may even be helpful in some patients with resistant ulcerative colitis. However, the recognition of potential complications of infliximab therapy has increased with the accumulated clinical experience. Results from trials of other biologic therapies directed at tumor necrosis factor alpha have been disappointing so far, although preliminary studies with biologics directed at adhesion molecules are encouraging. Growing appreciation of the importance of the enteric microflora in IBD has led to a considerable interest in manipulating intestinal bacteria for therapeutic benefit, and trials of both probiotics and prebiotics show promise.


Social support, neuropsychological performance, and depression in HIV infection.
The present study was designed to examine the impact of neuropsychological performance on the relationships between stress, social support, and depression in 217 HIV-infected men. Using path analysis, the contributions of four domains of cognitive functioning (memory, attention, executive function, and psychomotor speed), IQ, and relevant psychosocial variables to depression were evaluated. In the model which best fit the data, cognitive domains did not contribute directly to depression, but contributed significantly to psychosocial variables which affected levels of depression. Attention and executive function contributed to reduced illness-related disability; while higher IQ was associated with fewer stressful life events. Number of stressful life events and level of illness-related disability were associated with depressive symptoms. Higher IQ led to greater numbers of social contacts, which was associated with fewer reported symptoms of depression. These findings suggest that better neuropsychological performance may lead to reduced stress and perceived disability, and more available social contacts. By these multiple paths, different domains of cognitive ability contribute indirectly to ameliorating depression in HIV-infected men.


Smoking alters thromboxane metabolism in man.
Chronic smoking is a major risk factor of atherosclerosis and coronary heart disease. The measurement of three major thromboxane A2 metabolites, 11-dehydrothromboxane B2, 2,3-dinorthromboxane B2 and thromboxane B2, in the urines of 13 apparently healthy smokers (average 39 years, range 27-56 years) showed significantly elevated excretion rates for all thromboxane A2 metabolites as compared to 10 apparently healthy age-matched non-smokers (average 37 years, range 26-56 years). Importantly, characteristic alterations in the thromboxane A2 metabolite pattern were found in the urines of smokers. The contribution of 2,3-dinorthromboxane B2 to total measured excretion of thromboxane A2 metabolites was 59.2% in smokers (404.0 +/- 53.0 pg/mg creatinine) versus 19.4% in non-smokers (85.2 +/- 8.3 pg/mg creatinine), that of 11-dehydrothromboxane B2 35.7% in smokers (673.2 +/- 88.9 pg/mg creatinine) as compared to 75.5% in non-smokers (332.6 +/- 30.9 pg/mg creatinine). The contribution of thromboxane B2 (57.5 +/- 7.7 pg/mg creatinine in smokers versus 21.9 +/- 1.5 pg/mg creatinine in non-smokers) was similar at 5.1%. The excretion of cotinine, the major urinary metabolite of nicotine that correlates well with the reported daily cigarette consumption (r = 0.97, P less than 0.0001), showed a good correlation to thromboxane A2 metabolite excretion (2,3-dinorthromboxane B2: r = 0.92, P less than 0.0001; 11-dehydrothromboxane B2; r = 0.87, P less than 0.0001).


Multiple dimeric forms of human CD69 result from differential addition of N-glycans to typical (Asn-X-Ser/Thr) and atypical (Asn-X-cys) glycosylation motifs.
CD69 is expressed on the surface of all hematopoietically derived leukocytes and is suggested to function as a multipurpose cell-surface trigger molecule important in the development and activation of many different cell types. Human CD69 contains only a single consensus sequence for N-linked oligosaccharide addition within its extracellular domain (Asn-Val-Thr), yet exists as two distinct glycoforms that are assembled together into disulfide-linked homodimers and heterodimers. The molecular basis for human CD69 heterogeneity has remained elusive. In the current report we show that human CD69 glycoforms are generated before the egress of CD69 proteins from the endoplasmic reticulum to the Golgi and are synthesized under conditions where Golgi processing is inhibited, effectively ruling out the possibility that CD69 heterogeneity results from the differential processing of a single glycosylation site in the Golgi complex. Importantly, these data demonstrate that contrary to current belief, not one but two sites for N-glycan addition exist within the human CD69 extracellular domain and identify the second, "cryptic" CD69 N-glycan attachment site as the atypical Cys-containing glycosylation motif, Asn-Ala-Cys. The results in this study provide a molecular basis for human CD69 heterogeneity and show that multiple dimeric forms of human CD69 result from the variable addition of N-glycans to atypical and typical glycosylation motifs within the CD69 extracellular domain.


Breast cancer cell regulation by high-dose Vitamin D compounds in the absence of nuclear vitamin D receptor.
1alpha,25-dihydroxyvitamin D(3) (1,25D(3)) inhibits growth and induces apoptosis in breast cancer cells in vivo and in vitro. To examine the role of the Vitamin D receptor (VDR) in mediating the actions of 1,25D(3) at nanomolar and micromolar concentrations, mammary epithelial tumor cell lines generated in wild type (WT) and VDR knockout (VDRKO) mice were utilized. WT cells express VDR and are growth inhibited by 1,25D(3) and synthetic analogs EB1089 and CB1093 at 1nM concentrations, while VDRKO cells do not express VDR and are insensitive to Vitamin D compounds at concentrations up to 100nM. In the current studies, we have confirmed and extended these previous observations. At nanomolar concentrations of 1,25D(3) and all analogs tested, including EB1089, CB1093, MC1288, and KH1230, WT cells are growth inhibited and exhibit apoptotic morphology, while VDRKO cells show no growth inhibition or apoptosis. At concentrations of 1-10microM, however, 1,25D(3) and synthetic analogs induce growth inhibition and apoptotic morphology in both WT and VDRKO cell lines. These data indicate that nanomolar concentrations of 1,25D(3) and analogs mediate growth regulatory effects via mechanisms requiring the nuclear VDR, but that micromolar concentrations of Vitamin D compounds can exert non VDR-mediated effects.


Response of germfree animals to shock.
Many current models of septic shock in conventional (CV) rats utilize cecal ligation and perforation. That germfree (GF) status offered no increased protection in shock, compared with the effect on CV controls, was shown in early studies. Appropriate fluid therapy, however, did increase survival. Our laboratory's efforts to determine the influence of the GF rat's enlarged cecum on its early response to hemorrhagic shock can be summarized as follows. Ten litters of 8 GF rats each were randomly divided into four groups with two animals/group: CV control, GF control, CV cecectomized and GF cecectomized. Littermates were cecectomized at seven weeks and bled at 14 weeks. Under methoxyflurane anesthesia, the rats were cannulated (femoral artery), heparinized, restrained, and allowed to awaken. Blood pressure was maintained at 60 mmHg for 1 hr and at 50 mmHg for 3 hr by adjusting the height of a burette reservoir. In the GF cecectomized rats, 95% (19/20) survived, whereas only 50% (10/20) of the other three categories survived. Cecectomized GF rats required only 3% of their shed blood, whereas, the other three groups needed 10 to 15%. Cecum from the GF rat contains a 5-fold greater quantity of bioactive and vasoactive substances than the cecum of its CV control, and may cause these changes in basic cardiovascular parameters in GF control rats: decreased cardiac output, blood volume, heart weight, and vasoconstriction to epinephrine in mesenteric arterioles, plus increased hemoconcentration and blood viscosity. In cecectomised GF rats, these parameters return to the CV levels and help to protect the animal during the early hypovolemic trauma. Clearly, the rat's cecum produces significant cardiovascular effects that need to be considered when evaluating experimental models for trauma or stress.


Murine genotype influences the specificity, magnitude and persistence of murine mercury-induced autoimmunity.
Genetic factors are major contributors in determining the susceptibility to systemic autoimmune diseases. We studied the influence of genotype on systemic autoimmunity by treating female mice of the H-2s strains SJL/N, SJL/J, A.SW, and B10.S with mercuric chloride (HgCl2) for 10 weeks and then following autoantibody and tissue immune deposits during the subsequent 12 months. All strains developed antinucleolar antibodies (ANoA) of the IgG class which reacted in immunoblotting with a 34-kDa nucleolar protein identified as fibrillarin. The titre of ANoA attained after 10 weeks' treatment varied from 1:1,280 to 1:20,480 in the order: A.SW > SJL > > B10.S. Following cessation of HgCl2 treatment ANoA and antifibrillarin antibodies (AFA) persisted for up to 12 months, although some B10.S mice showed pronounced reduction not only of their autoantibody titres, but also systemic immune deposits when compared to other H-2s strains. A second set of autoantibodies targeted chromatin and in some mice specifically histones, and were distinguished from the ANoA by a rapid decline after treatment and a susceptibility linked to the non-H-2 genes of the SJL. Tissue levels of mercury remained elevated above untreated controls throughout the study period, suggesting that the mercury detected in lymphoid tissues may provide stimulation of lymphoid cells specific for fibrillarin for a considerable period after exposure has ceased. We conclude that H-2 as well as non-H-2 genetic factors distinctly influence not only the susceptibility to induction of autoimmunity, but also the specificity and magnitude of the response.


Panniculitis mimicking lupus erythematosus profundus: a new histopathologic finding in malignant atrophic papulosis (Degos disease).
We present the case of a 57-year-old woman with a 1-year history of a cutaneous eruption clinically and histopathologically characteristic of Degos disease. In one of the two cutaneous biopsy specimens taken from the trunk lesions, the histopathology consisted of necrosis and sclerosis of the subcutaneous lobules, a finding that to our knowledge has not been previously described in the cutaneous lesions of Degos disease. Two months after cutaneous biopsies were taken, the patient developed ptosis and an episode of acute abdominal pain; intestinal perforation and many characteristic lesions of visceral Degos disease involving the entire small bowel were noted at laparotomy.


Distribution of compensable hearing loss in industry.
Most State Workers' Compensation Acts base their determinations of impairment for occupational hearing loss on the formula developed by the American Academy of Ophthalmology and Otolaryngology and adopted by the American Medical Association in 1971. The professional literature tends to focus on the monetary awards for total hearing loss and thus gives the impression that extremely severe hearing loss is common among industrial workers. A study of 8,953 industrial employees shows that 1,120, or 12.5% are compensable. Of these, 61.5% have 5% impairment or less; 74.1% have no more than 10% impairment, and 86.7% are 20% impaired. These findings suggest that hearing professionals have the opportunity to make a major social-economic contribution to industrial management and labor by applying their expertise to the prevention of occupational hearing loss.


Autophagy as a mechanism for anti-angiogenic therapy resistance.
Autophagy is a lysosomal-dependent degradation process that is highly conserved and maintains cellular homeostasis by sequestering cytosolic material for degradation either non-specifically by non-selective autophagy, or targeting specific proteins aggregates by selective autophagy. Autophagy serves as a protective mechanism defending the cell from stressors and also plays an important role in enabling tumor cells to overcome harsh conditions arising in their microenvironment during growth as well as oxidative and non-oxidative injuries secondary to therapeutic stressors. Recently, autophagy has been implicated to cause tumor resistance to anti-angiogenic therapy, joining an existing literature implicating autophagy in cancer resistance to conventional DNA damaging chemotherapy and ionizing radiation. In this review, we discuss the role of angiogenesis in malignancy, mechanisms of resistance to anti-angiogenic therapy in general, the role of autophagy in driving malignancy, and the current literature in autophagy-mediated anti-angiogenic therapy resistance. Finally, we provide future insight into the current challenges of using autophagy inhibitors in the clinic and provides tips for future studies to focus on to effectively target autophagy in overcoming resistance to anti-angiogenic therapy.


Wasp venom proteins: phospholipase A1 and B.
Three major venom proteins from different species of wasps have been isolated and characterized. They are hyaluronidase, phospholipase, and antigen 5 of as yet unknown biochemical function. These three proteins are allergens in wasp venom-sensitive persons. The species of wasps studied, of the genus Polistes, were annularis, carolina, exclamans, fuscatus, and instabilis. Antigen 5 and phospholipase from wasp venoms were shown to be antigenically distinct from homologous proteins of yellowjacket venoms. The venom phospholipase from wasp, as well as that from yellowjacket (Vespula germanica), appears to have dual enzymatic specificities of the A1 and B types. That is, hydrolysis takes place at the 1-acyl residue of phosphatidylcholine and at the 1- or 2-acyl residue of lysophosphatidylcholine.


A mammalian functional nitrate reductase that regulates nitrite and nitric oxide homeostasis.
Inorganic nitrite (NO(2)(-)) is emerging as a regulator of physiological functions and tissue responses to ischemia, whereas the more stable nitrate anion (NO(3)(-)) is generally considered to be biologically inert. Bacteria express nitrate reductases that produce nitrite, but mammals lack these specific enzymes. Here we report on nitrate reductase activity in rodent and human tissues that results in formation of nitrite and nitric oxide (NO) and is attenuated by the xanthine oxidoreductase inhibitor allopurinol. Nitrate administration to normoxic rats resulted in elevated levels of circulating nitrite that were again attenuated by allopurinol. Similar effects of nitrate were seen in endothelial NO synthase-deficient and germ-free mice, thereby excluding vascular NO synthase activation and bacteria as the source of nitrite. Nitrate pretreatment attenuated the increase in systemic blood pressure caused by NO synthase inhibition and enhanced blood flow during post-ischemic reperfusion. Our findings suggest a role for mammalian nitrate reduction in regulation of nitrite and NO homeostasis.


Choroid plexus macrophages proliferate and release toxic factors in response to feline immunodeficiency virus.
Recent observations have suggested that lentiviruses stimulate the proliferation and activation of microglia. A similar effect within the dense macrophage population of the choroid plexus could have significant implications for trafficking of virus and inflammatory cells into the brain. To explore this possibility, we cultured fetal feline macrophages and examined their response to feline immunodeficiency virus (FIV) or the T-cell-derived protein, recombinant human CD40-ligand trimer (rhuCD40-L). The rhCD40-L was the most potent stimulus for macrophage proliferation, often inducing a dramatic increase in macrophage density. Exposure to FIV resulted in a small increase in the number of macrophages and macrophage nuclei labeled with bromodeoxyuridine. The increase in macrophage density after FIV infection also correlated with an increase in neurotoxic activity of the macrophage-conditioned medium. Starting at 16-18 weeks postinfection, well after the peak of viremia, a similar toxic activity was detected in cerebrospinal fluid (CSF) from FIV-infected cats. Toxicity in the CSF increased over time and was paralleled by strong CD18 staining of macrophages/microglia in the choroid plexus and adjacent parenchyma. These results suggest that lentiviral infection of the choroid plexus can induce a toxic inflammatory response that is fueled by local macrophage proliferation. Together with the observation of increasing toxic activity in the CSF and increased CD18 staining in vivo, these observations suggest that choroid plexus macrophages may contribute to an inflammatory cascade in the brain that progresses independently of systemic and CSF viral load.


Demonstration of two pools of albumin-bound fatty acids.
The uptakes of albumin-bound nonesterified fatty acids and of [1-14C]palmitic acid complexed to albumin by the isolated perfused rat liver were compared. During perfusion, the rate of uptake of nonesterified fatty acids decreased and became zero when the fatty acid:albumin molar ratio reached 0.3, but the rate of uptake of radioactive palmitic acid remained constant. This finding suggests the existence of two pools of fatty acids bound to albumin with different fractional turnover rates. This view was supported by the fact that when delipidated albumin complexed in vitro to radioactive and nonradioactive fatty acids was used no difference was observed between the uptakes of nonesterified fatty acids and radioactive fatty acids by perfused liver. Similar results were found with albumin-bound radioactive fatty acid in vivo (obtained from rats fed radioactive palmitic acid), showing a homogeneous distribution of the label in both pools. The existence of two nonesterified fatty acid pools in plasma would arise from the differences in the nature of bonds between fatty acid and albumin molecules, which could determine the rate of exchange of fatty acids between the albumin-bound and soluble forms preceding their uptake by the cells.


Alterations in the coronary circulation in hypertrophied ventricles.
During the past decade our understanding of the complex interaction between cardiac muscle and coronary vascular growth has increased substantially. Some types of cardiac hypertrophy, for example, left ventricular hypertrophy secondary to hyperthyroidism, are associated with increased coronary vascular growth. However, in most animal preparations of hypertrophy and in several clinical types of hypertrophy of the left and/or right ventricles, pathologic cardiac enlargement impairs the ability of the coronary circulation to allow normal increases and perfusion in response to intense dilator stimuli. In general, clinical studies have demonstrated far more profound abnormalities than studies in experimental animals. These observations provide a plausible explanation of why patients with hypertrophied ventricles often exhibit signs and symptoms of myocardial ischemia in the absence of coronary obstructive disease. The recent observation that experimentally produced left ventricular hypertrophy secondary to renal hypertension augments infarct size and the incidence of sudden lethal arrhythmias has additional implications relevant to the interaction between cardiac hypertrophy and myocardial perfusion. Although coronary reserve is impaired in many types of pathologic hypertrophy, the anatomic or biochemical basis for these observations remains elusive.


Mesenchymal Stromal Cells Disrupt mTOR-Signaling and Aerobic Glycolysis During T-Cell Activation.
Mesenchymal stromal cells (MSCs) possess numerous regenerative and immune modulating functions. Transplantation across histocompatibility barriers is feasible due to their hypo-immunogenicity. MSCs have emerged as promising tools for treating graft-versus-host disease following allogeneic stem cell transplantation. It is well established that their clinical efficacy is substantially attributed to fine-tuning of T-cell responses. At the same time, increasing evidence suggests that metabolic processes control T-cell function and fate. Here, we investigated the MSCs' impact on the metabolic framework of activated T-cells. In fact, MSCs led to mitigated mTOR signaling. This phenomenon was accompanied by a weaker glycolytic response (including glucose uptake, glycolytic rate, and upregulation of glycolytic machinery) toward T-cell activating stimuli. Notably, MSCs express indoleamine-2,3-dioxygenase (IDO), which mediates T-cell suppressive tryptophan catabolism. Our observations suggest that IDO-induced tryptophan depletion interferes with a tryptophan-sufficiency signal that promotes cellular mTOR activation. Despite an immediate suppression of T-cell responses, MSCs foster a metabolically quiescent T-cell phenotype characterized by reduced mTOR signaling and glycolysis, increased autophagy, and lower oxidative stress levels. In fact, those features have previously been shown to promote generation of long-lived memory cells and it remains to be elucidated how MSC-induced metabolic effects shape in vivo T-cell immunity.


Endovascular treatment of side wall aneurysms using a liquid embolic agent: a US single-center prospective trial.
Onyx HD-500 is a liquid embolic agent consisting of ethylene vinyl alcohol copolymer dissolved in dimethylsulfoxide and mixed with tantalum. This viscous embolic agent was designed to treat intracranial side wall aneurysms, but there have been no prospective published series from the United States. From this early experience, we developed several protocol revisions, technical details, and clinical pearls that have not been published for liquid embolic embolization of aneurysms. We present our single-center prospective series of patients treated with Onyx HD-500 from a multicenter, randomized, controlled trial. Thirteen patients received Onyx HD-500, and their ages ranged from 43 to 81 years. Twelve patients had aneurysms on the internal carotid artery, and 1 patient had an aneurysm the vertebral artery. Every patient had an immediate postangiographic result with 90% or more occlusion by an independent core laboratory assessment. In 1 patient, the Onyx HD-500 injection was aborted, and the aneurysm was embolized with coils. Eleven of 13 patients (85%) underwent 6-month follow-up angiography that demonstrated persistent durable occlusion with no recanalization. There was 1 complication (8%) and no deaths. This is the only prospective series of intracranial aneurysms treated with Onyx HD-500 in the United States. This is also the first publication that describes detailed procedure techniques, recommended protocol revisions, lessons learned from early complications, clinical pearls, and advantages and disadvantages of liquid embolic embolization of aneurysms.


Receptor signaling and neutral endopeptidase are involved in the resistance of C-type natriuretic peptide to human mesangial proliferation and collagen-IV expression.
C-type natriuretic peptide (CNP) is regarded as a local, paracrine hormone to regulate vascular tone and cell proliferation. Although several in vivo studies have documented that CNP exerts the inhibitory effects on mesangial cells (MCs) proliferation and collagen production, a limited number of studies exist about the resistance of CNP to MCs proliferation in vitro. Besides, whether its receptor signaling and neutral endopeptidase (NEP) are involved remains unclear. In the present study, human MCs were incubated in serum-containing medium in the absence or presence of CNP (0, 10 and 100 pM) for 24, 48 and 72 hours, respectively. CNP administration significantly suppresses MCs proliferation and collagen-IV (Col-IV) expression in a time-dependent and dose-dependent manner. As a down-stream signal molecule of CNP activation, the expressions of natriuretic peptide receptor (NPR)-B, cyclic guanosine monophosphate-dependent protein kinases II and NPR-C were obviously augmented, whereas NEP expression was significantly decreased after CNP treatment. In conclusion, receptor signaling and NEP are involved in the resistance of CNP to human mesangial proliferation and Col-IV expression.


Iron deficiency anemia in pregnancy.
Anemia is the most frequent derailment of physiology in the world throughout the life of a woman. It is a serious condition in countries that are industrialized and in countries with poor resources. The main purpose of this manuscript is to give the right concern of anemia in pregnancy. The most common causes of anemia are poor nutrition, iron deficiencies, micronutrients deficiencies including folic acid, vitamin A and vitamin B12, diseases like malaria, hookworm infestation and schistosomiasis, HIV infection and genetically inherited hemoglobinopathies such as thalassemia. Depending on the severity and duration of anemia and the stage of gestation, there could be different adverse effects including low birth weight and preterm delivery. Treatment of mild anemia prevents more severe forms of anemia, strictly associated with increased risk of fetal-maternal mortality and morbidity.


Identification and validation of a virus-inducible ta-siRNA-generating TAS4 locus in tomato.
Trans-acting small interfering RNAs (ta-siRNAs) are a class of endogenous small RNA, associated with posttranscriptional gene silencing. Their biogenesis requires an initial microRNA (miRNA)-mediated cleavage of precursor RNA. Around 20 different ta-siRNA-producing loci (TASs), whose sequences are conserved, are reported in plants. In tomato, two TAS gene families have been identified, which are found to target auxin response factor gene and bacterial spot disease resistance protein Bs4 gene. Using high-throughput computational and experimental approach, we identified a new locus-producing ta-siRNA in tomato. We have also identified the putative miRNA regulating the production of ta-siRNA from this locus. The ta-siRNAs generated from TAS4 were up-regulated upon infection with a DNA virus. The potential targets of ta-siRNAs were predicted to be variety of proteins including MYB transcription factors and cell cycle regulators for some of the ta-siRNAs produced.


[The use of modern ceramics for inlays and onlays].
If ceramic inlays and onlays are considered in restorative work, some operations which, more than in other areas of dental engineering, decide upon the success or failure should be given special attention. During the preparation of ceramic inlays care should be taken to produce well rounded rather than rectangular edges approximally. In the case of onlays there should ideally be a smooth circular step rounded axially with a sharp-edged near-rectangular interface with the non-ground tooth. Ceramic inlays and onlays are best inserted with the adhesive technique, which provides for an improved strength of the ceramic material, an adequate marginal adaptation and a satisfactory cosmetic appearance. As long-term results are not yet available, the use of ceramic inlays and onlays is still experimental.


New applications of nanotechnology for neuroimaging.
Advances in nanotechnology have the potential to dramatically enhance the detection of neurologic diseases with targeted contrast agents and to facilitate the delivery of focused therapies to the central nervous system. We present the physicochemical rationale for their use, applications in animal models, and ongoing clinical trials using these approaches. We highlight advances in the use of nanoparticles applied to brain tumor imaging, tumor angiogenesis, neurodegeneration, grafted stem cells, and neuroprogenitor cells.


Three-dimensional imaging of craniomaxillofacial structures with a standard personal computer.
To implement 3D-reconstruction of CT and MR data by a standard MS-DOS personal computer. User-specific software has been developed for the 3D-reconstruction and quantitative evaluation of hard and soft tissues of the skull. The software displays a 3D-reconstruction and secondary reformatted vertical sections within 4-30 s on the monitor. The 3D-structures can be evaluated quantitatively with a freely-superimposable grid. Distances or angles between two landmarks can be measured directly. Various tools for the simulation of surgical treatment are available. Gross skeletal and soft-tissue malformations, topographical relations and the degree of asymmetry of severe maxillofacial deformities can be evaluated in more detail. Access to a readily available low-cost computer system for 3D-evaluation of the head will enable a larger number of clinicians to use 3D-methods in diagnosis and treatment planning. The off-line computing system permits a higher of flexibility independent of any computing centre.


Tick-host-pathogen interactions in Lyme borreliosis.
Borrelia burgdorferi, the spirochetal agent of Lyme borreliosis, is predominantly transmitted by Ixodes ticks. Spirochetes have developed many strategies to adapt to the different environments that are present in the arthropod vector and the vertebrate host. This review focuses on B. burgdorferi genes that are preferentially expressed in the tick and the vertebrate host, and describes how selected gene products facilitate spirochete survival throughout the enzootic life cycle. Interestingly, B. burgdorferi also enhances expression of specific Ixodes scapularis genes, such as TROSPA and salp15. The importance of these genes and their products for B. burgdorferi survival within the tick, and during the transmission process, will also be reviewed. Moreover, we discuss how such vector molecules could be used to develop vector-antigen-based vaccines to prevent the transmission of B. burgdorferi and, potentially, other arthropod-borne microbes.


Massive cerebral air embolism after cardiopulmonary resuscitation.
We report a case of massive intracerebral air embolism after cardiopulmonary resuscitation in a patient with a fatal head injury. There was no pneumothorax or extravascular pneumocephalus, however, air was found in the internal carotid artery. Massive cerebral air embolism may occur after entrance of air into the circulatory system via ruptured pulmonary vessels during cardiopulmonary resuscitation.


Raman microspectroscopy as an identification tool within the phylogenetically homogeneous 'Bacillus subtilis' group.
Vibrational methods have multiple advantages compared to more classic, chemotaxonomic and even molecular microbial tools for the identification of bacteria. Nevertheless, their definite breakthrough in diagnostic microbiology laboratories is determined by their identification potential. This paper reports on the profound evaluation of Raman spectroscopy to identify closely related species by means of 68 Bacillus strains that are assigned or closely related to the phylogenetically homogeneous 'Bacillus subtilis'-group (sensu stricto). These strains were chosen to represent biological variation within the selected species and to create a realistic view on the possibilities of this technique The evaluation resulted in 49/54 correct identifications at the species level for intern and 15/19 for extern testing. The correct identification of strains, which were not represented in the training set, supports the potential as an identification tool within the 'B. subtilis group'. Considering the vague borderline between the species studied, Raman spectroscopy can be regarded here as a promising application for identifications at the species level.


Production of non-fucosylated antibodies by co-expression of heterologous GDP-6-deoxy-D-lyxo-4-hexulose reductase.
All IgG-type antibodies are N-glycosylated in their Fc part at Asn-297. Typically, a fucose residue is attached to the first N-acetylglucosamine of these complex-type N-glycans. Antibodies lacking core fucosylation show a significantly enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) and an increased efficacy of anti-tumor activity. In cases where the clinical efficacy of an antibody is to some extent mediated by its ADCC effector function, afucosylated N-glycans could help to reduce dose requirement and save manufacturing costs. Using Chinese hamster ovary (CHO) cells as a model, we demonstrate here that heterologous expression of the prokaryotic enzyme GDP-6-deoxy-d-lyxo-4-hexulose reductase within the cytosol can efficiently deflect the fucose de novo pathway. Antibody-producing CHO cells that were modified in this way secrete antibodies lacking core fucose as demonstrated by MALDI-TOF mass spectrometry and HPAEC-PAD monosaccharide analysis. Engineering of the fucose de novo pathway has led to the construction of IgGs with a strongly enhanced ADCC effector function. The method described here should have broad practical applicability for the development of next-generation therapeutic antibodies.


Magic shotgun methods for developing drugs for CNS disorders.
Extract: Development of novel therapeutic entities with which to treat disorders of the central nervous system (CNS) that are both more effective and more specific, poses significant challenges to the drug discovery industry. The normal focus of drug research is the search for a "magic bullet," which acts on a specific protein (or receptor), ideally with no other interactions with other proteins. These are termed "clean" drugs, as they have a single action with few side effects. However, most common CNS disorders are highly polygenic in nature, i.e., they are controlled by complex interactions between numerous gene products. As such, these conditions do not exhibit the single gene defect basis that is so attractive for the development of highly-specific drugs largely free of major undesirable side effects ("the magic bullet"). Secondly, the exact nature of the interactions that occur between the numerous gene products typically involved in CNS disorders remain elusive, and the biological mechanisms underlying mental illnesses are poorly understood.


Spousal bereavement: the lived experience of young Canadian widows.
A phenomenological study was conducted to understand the lived experience of spousal bereavement from the perspective of young Canadian widows. Five themes emerged following inductive analysis of interview transcripts conducted with five women who were under the age of 45 at the time of their husband's death: (a) "Losses"; (b) "Who Am I?"; (c) "Staying Connected through Memories"; (d) "Living through the Firsts"; and (e) "Support Systems." Increased understanding from the perspective of the bereaved women, along with strategies and interventions for those working with this group of women, may provide health care professionals with skills to better assist this client population.


Diagnostic precision of mentally estimated home blood pressure means.
Paper home blood pressure (HBP) charts are commonly brought to physicians at office visits. The precision and accuracy of mental calculations of blood pressure (BP) means are not known. A total of 109 hypertensive patients were instructed to measure and record their HBP for 1 week and to bring their paper charts to their office visit. Study section 1: HBP means were calculated electronically and compared to corresponding in-office BP estimates made by physicians. Study section 2: 100 randomly ordered HBP charts were re-examined repetitively by 11 evaluators. Each evaluator estimated BP means four times in 5, 15, 30, and 60 s (random order) allocated for the task. BP means and diagnostic performance (determination of therapeutic systolic and diastolic BP goals attained or not) were compared between physician estimates and electronically calculated results. Overall, electronically and mentally calculated BP means were not different. Individual analysis showed that 83% of in-office physician estimates were within a 5-mmHg systolic BP range. There was diagnostic disagreement in 15% of cases. Performance improved consistently when the time allocated for BP estimation was increased from 5 to 15 s and from 15 to 30 s, but not when it exceeded 30 s. Mentally calculating HBP means from paper charts can cause a number of diagnostic errors. Chart evaluation exceeding 30 s does not significantly improve accuracy. BP-measuring devices with modern analytical capacities could be useful to physicians.


Isolation and molecular analysis of inv dup(15) and construction of a physical map of a common breakpoint in order to elucidate their mechanism of formation.
An inverted duplication of chromosome 15 [inv dup(15)] is the most common supernumerary marker chromosome, comprising approximately 50% of all chromosomes in this class. Structurally, the inv dup(15) is a mirror image with the central axis defining a distal break within either the heterochromatic alpha-satellite array or along the euchromatin in the long (q) arm of the chromosome. There are several types of inv dup(15), classified by the amount of euchromatic material present. Generally, they are bisatellited, pseudodicentric and have a breakpoint in 15q11-q14. A suggested mechanism of formation of inv dup(15) involves illegitimate recombination between homologous chromosomes followed by nondisjunction and centromere inactivation. The proximal portion of chromosome 15 contains several low-copy repeat sequence families and it has been hypothesized that errors in pairing among these repeats may result in structural rearrangements of this chromosome including the inv dup(15). To test this hypothesis and to determine the mechanism of formation, the inv dup(15) from four cases was isolated in somatic cell hybrids and polymerase chain reaction microsatellite markers were used to determine the origin of exchange. Two appeared to result from interchromosomal and two from intrachromosomal exchange, one of which occurred post-recombination. In addition, a detailed physical map of the breakpoint region in the largest inv dup(15) was constructed placing eight new sequence-tagged sites and ten new bacterial artificial chromosome markers in the region.


Pericardial fat mimicking pericardial effusion on two-dimensional echocardiography.
A 78-year-old overweight woman with diabetes mellitus, bronchial asthma, and Sheehan's syndrome on chronic steroid therapy presented with mild short-lived hematemesis, significant hypotension disproportionate to the degree of bleeding and radiographic evidence of cardiomegaly. Endoscopy showed duodenal ulcer. During evaluation of the unexplained brief hypotension and cardiomegaly, 2D-echocardiogram demonstrated anterior and posterior echo-free spaces consistent with large pericardial effusion (PE). However, subsequent elective surgical pericardiotomy unexpectedly revealed large amounts of pericardial fat. Pericardial fat was also noted on magnetic resonance imaging of the chest. Our case illustrates a potential pitfall of 2D-echocardiography in the diagnosis of PE.


Connectionism and an inescapable defect.
Linear connectionist models of neurocomputing show how input patterns may be recognized, stored, compared, and recalled for output in serial-parallel, quasi-Hebbian networks. This aids the design of hardware and software for better robotics, while offering useful insights to neuroscientists studying sensorimotor systems, but connectivity via quasi-Hebbian nodes and back-propagation layers alone cannot show us how vertebrate cerebellum, allocortex, and neocortex work.


Sweden.
Depression increases risk of having first stroke.


[A European discussion about stem cells for therapeutic use].
Stem cells as a source material for growing cellular transplants to repair dysfunctional organs appear to be a new challenge for medical science. Though stem cells are also present in foetal and adult organs, embryonic stem cells from the pre-implantation embryo in particular have the potency to proliferate easily in vitro and the capacity to differentiate into all the body's organ-specific cells. Therefore, these are the ideal cells for developing new cell transplantation therapies for diseases such as Parkinson's disease, diabetes mellitus and heart failure. The use of spare in vitro fertilization (IVF) embryos or pre-implantation embryos specially created to harvest human embryonic stem cells is, however, controversial and an ethical problem. In a European discussion platform organised by the European Commission Research Directorate-General, the status quo of the progress was presented and subsequently commented upon and discussed in terms of medical-ethical, social, industrial and patient interests. The expectations of this new medical technology were high, but clinical trials seem only acceptable once the in vitro differentiation of stem cells can be adequately controlled and once it is known how in vitro prepared stem cells behave after implantation. The ethical justification of the use of in vitro pre-implantation embryos remains controversial. The prevailing view is that the interests of severely ill patients for whom no adequate therapy exists, surmounts the interest of protection of a human in vitro pre-implantation embryo, regardless of whether it was the result of IVF or of transplantation of a somatic cell nucleus of the patient in an enucleated donor egg cell (therapeutic cloning).


Evaluation of rebreathing potential on bedding for infant use.
Rebreathing is thought to be associated with sudden infant death syndrome (SIDS). The aim of the present study was to evaluate the rebreathing potential of different types of Japanese infant bedding. The rebreathing potential of various combinations of infant bedding was measured using a mechanically simulated breathing model. The types of bedding included five types of mattresses, four types of o-nesyo sheets (waterproof sheets) and a towel. The half-life of the expiratory CO2 concentration, t1/2-value was calculated as the index of the rebreathing potential. The softness of the bedding was also measured. There was a moderate proportional correlation between the t1/2-value and the softness (correlation coefficient = 0.509). When a new hard infant mattress was used, the t1/2-values were 13.6-14.1 s, and when o-nesyo sheet was added, the values were 14.1-16.2 s. When other mattresses were used with the o-nesyo sheet, the values were 14.1-19.2 s. Adding a towel onto the bedding, the t1/2-value (18.5-22.3 s) was prolonged without exception. It is difficult to estimate the rebreathing potential of the bedding on the basis its appearance or its softness. All infants should be placed on appropriate bedding in case they turn to a prone-sleeping position. Our recommendations to avoid rebreathing are as follows: (i) a new hard mattress specifically designed for babies should be used; (ii) a towel should not be used; (iii) an o-nesyo sheet may be used with a new hard infant mattress if necessary.


Prospective randomized clinical trial comparing the effectiveness of immediate arthroscopic stabilization versus immobilization and rehabilitation in first traumatic anterior dislocations of the shoulder.
Our purpose was to compare the effectiveness of traditional treatment with immediate arthroscopic stabilization in young patients who have sustained a first traumatic anterior dislocation of the shoulder. Forty skeletally mature patients younger than 30 years of age were randomly allocated to immobilization for 3 weeks followed by rehabilitation (group T) or arthroscopic stabilization (within 4 weeks of injury) followed by an identical immobilization and rehabilitation protocol (group S). A blinded research assistant performed all follow-up evaluations. The dominant arm was involved in 35% of subjects. The injury occurred in a sporting event in 70% of subjects. At 24 months, there was a statistically significant difference in the rate of redislocation (T = 47%, S = 15.9%, P = .03). An intention-to-treat analysis comparing disease-specific quality of life using the validated Western Ontario Shoulder Instability (WOSI) index showed statistically significantly better results in the surgically treated group at the 33 months (T = 633.93 v S = 287.1, P = .03) and no significant difference in range of motion. At an average 32 months follow-up, a significant reduction in redislocation and improvement in disease-specific quality of life is afforded by early arthroscopic stabilization in patients less than 30 year of age with a first, traumatic, anterior dislocation of the shoulder.


Nutritional composition of dishes commonly consumed by Japanese Brazilians in São Paulo, Brazil.
To calculate the nutritional composition of commonly consumed Brazilian foods and beverages to analyze dietary intake data obtained with a quantitative food frequency questionnaire in a colorectal adenoma case-control study in Japanese Brazilians. Weighed recipes were collected in São Paulo, Brazil and analyzed using NutriBase Clinical Nutrition Manager. A total of 387 recipes for 76 dishes commonly consumed by Japanese Brazilians were collected: 30 composite main course dishes, 26 composite vegetable dishes, 19 snack foods and desserts, and one beverage. The nutritional composition (energy and 32 macronutrients and micronutrients) was calculated per 100 g for each dish. We provided, for the first time, complete and up-to-date calculated nutritional composition data for commonly consumed Brazilian food items, which are essential to assess the current dietary intake among Japanese Brazilians.


Investigation of elastic features of aorta and color M-mode flow propagation velocity (APV) of descending aorta in the patients with ischemic and non-ischemic dilated cardiomyopathy.
Aortic flow propagation velocity (APV) is a novel echocardiographic parameter used in coronary artery disease. It has also been used for the evaluation of aortic stiffness. In the present study, APV was measured in patients with ischemic and non-ischemic dilated cardiomyopathy (DCM) and was compared with the parameters of aortic stiffness such as aortic distensibility (AD) and aortic strain (AS). A total of 140 patients who had undergone coronary angiographic imaging were included in the study. Out of these patients, 44 had ischemic DCM, 46 had non-ischemic DCM, and 50 had normal coronary angiography (control group). AS, AD, and APV were calculated echocardiographically. One-way analysis of variance (ANOVA) and the Kruskal-Wallis test were used to compare continuous variables between the groups, while the categorical variables were compared using Pearson's Chi square test. Pearson's correlation test was used to investigate the parameters associated with APV, AS, and AD. Ischemic DCM and non-ischemic DCM groups differed significantly. The comparison of these groups with the control group, in terms of AS, AD, and APV values (ANOVA p < 0.001 for all) also showed a significant difference. APV was found to be significantly correlated with AS (r = 0.645, p < 0.001) and AD (r = 0.604, p < 0.001). In ROC analysis, the area under the curve (AUC) value for APV was 0.999 (p = 0.000) for detection of patients ischemic DCM and non-ischemic DCM. APV may be considered to be a novel and a simple echocardiographic marker, for both, distinguishing ischemic from non-ischemic DCM as well as for the presence of dilated cardiomyopathy with or without critical coronary artery disease.


The impact of oral anticoagulation on time to surgery in patients hospitalized with hip fracture.
Current clinical guidelines recommend expedited repair of hip fracture to reduce morbidity and mortality. A significant number of hip fracture patients have concomitant cardiovascular disease requiring anticoagulation. Vitamin K antagonists (VKAs), which have been traditionally used, might be associated with an increased time to surgery (TTS) and it remains unknown what effect direct oral anticoagulants (DOACs) have on this metric. Our objective is to determine how anticoagulation with a VKA or DOAC affects TTS. This is a case control study comparing TTS in consecutively admitted hip fracture patients receiving either a DOAC or VKA with age- and gender-matched controls between January 1, 2010 and March 24, 2014. The primary end point is TTS, which is defined as the time elapsed from admission to surgery. Secondary end points include the rate of stroke, death, bleeding and VTE during admission. Of 2258 patients, 233 were on a VKA while 27 were on a DOAC. Median TTS seems to be longer in patients receiving a DOAC or a VKA when compared to controls. (40 h vs. 26.2h). The DOAC group tended to have longer median TTS when compared to the VKA groups (66.9h vs. 39.4h) There was no difference in the rate of stroke, death, bleeding and VTE during admission. Patients on anticoagulation prior to admission for hip fracture experienced longer delays in surgery when compared to patients not receiving anticoagulation. Patients on a DOAC experienced the longest surgical delay.