Need for electroencephalogram video confirmation of atypical absence seizures in children with Lennox-Gastaut syndrome.
Children with childhood epileptic encephalopathy (Lennox-Gastaut syndrome) frequently have both multiple seizure types and nonepileptic stereotyped events that are difficult to differentiate. We hypothesize that electroencephalogram (EEG) video monitoring is essential for correct identification of atypical absence seizures in this population. All video/EEG monitoring records on patients with confirmed Lennox-Gastaut syndrome between September 1992 and December 1996 were reviewed for clinical events and EEG changes. A subset of patients with suspected atypical absence seizures during the video/EEG formed the cohort for analysis. Thirty-eight patients had 48 monitoring periods ranging from 1 to 4 days (mean, 2.2 days). Twenty-six monitoring periods captured suspected atypical absence seizures and formed the study cohort. Suspected atypical absence seizures were epileptic seizures in only 27% (7 of 26) of the study cohort. By contrast, parents reliably and correctly identified tonic, atonic, and tonic-clonic seizures in the study cohort. Reliable diagnosis and subsequent counting of atypical absence seizures in patients with Lennox-Gastaut syndrome cannot be made on the basis of observation and/or history alone. Future outpatient studies of investigational anticonvulsant medications for patients with Lennox-Gastaut syndrome should consider parental counts of atypical absence seizures unreliable. We recommend that video/EEG monitoring be done on all Lennox-Gastaut syndrome patients with suspected atypical absence seizures not controlled by medication.


Ethical issues in the treatment of severe psychopathology in university and college counseling centers.
Increasing numbers of students with severe personality disorders are presenting for psychological services at college and university counseling centers. The influx of these students poses a number of ethical dilemmas for counseling centers. Clinical decisions about appropriate treatment modalities, philosophical decisions about agency mission, and available resources to carry defined missions converge and influence ethical decisions in this area. It is misguided kindness, as well as being ethically unwise and legally risky, to attempt to carry out a treatment mission with inadequate resources. It is not abandonment to have selection criteria grounded in the treatment literature and executed with fairness if the duty to refer is upheld.


Formaldehyde oxime <--> nitrosomethane tautomerism.
Formaldehyde oxime <--> nitrosomethane tautomerism, isomeric nitrone, and their common cations and anions are studied with Gaussian-2 theory using MP2(full)/6-31G geometries and with density functional theory using B3LYP/6-311+G**. Geometrical parameters, harmonic vibrational frequencies, relative stabilities, conformational stabilities, and ionization energies are compared with experimental gas-phase data when available. The formaldehyde oxime <--> nitrosomethane tautomerism is compared with the amide <--> imidol, imine <--> enamine, keto <--> enol, and nitro <--> aci-nitro tautomeric processes. Solvent effects are estimated by the self-consistent isodensity polarizable continuum model (SCIPCM). The influence of hydrogen bonding interactions with the solvent is addressed by including two water molecules. In the final evaluation, formaldehyde oxime is 15.8 kcal/mol more stable than nitrosomethane when the aqueous solvation correction of 3.8 kcal/mol is applied to the G2 energies. Unsolvated formaldehyde oxime is estimated to be 11.1 kcal/mol more stable than nitrone. The estimated gas-phase ionization energies (G2) are 362.5 kcal/mol for formaldehyde oxime, 350.6 kcal/mol for nitrosomethane, and 351.4 kcal/mol for nitrone.


Monocyte adhesion to xenogeneic endothelium during laminar flow is dependent on alpha-Gal-mediated monocyte activation.
Monocytes are the predominant inflammatory cell recruited to xenografts and participate in delayed xenograft rejection. In contrast to allogeneic leukocytes that require up-regulation of endothelial adhesion molecules to adhere and emigrate into effector tissues, we demonstrate that human monocytes adhere rapidly to unstimulated xenogeneic endothelial cells. The major xenoantigen galactosealpha(1,3)galactosebeta(1,4)GlcNAc-R (alpha-gal) is abundantly expressed on xenogeneic endothelium. We have identified a putative receptor for alpha-gal on human monocytes that is a member of the C-type family of lectin receptors. Monocyte arrest under physiological flow conditions is regulated by alpha-gal, because cleavage or blockade results in a dramatic reduction in monocyte adhesion. Recruitment of human monocytes to unactivated xenogeneic endothelial cells requires both alpha(4) and beta(2) integrins on the monocyte; binding of alpha-gal to monocytes results in rapid activation of beta(2), but not alpha(4), integrins. Thus, activation of monocyte beta(2) integrins by alpha-gal expressed on xenogeneic endothelium provides a mechanism that may explain the dramatic accumulation of monocytes in vivo.


Derivation of human embryonic stem cell lines after blastocyst microsurgery.
Embryonic stem cells (ESCs) are derived from the inner cell mass (ICM) of the blastocyst. Because of their ability to differentiate into a variety of cell types, human embryonic stem cells (hESCs) provide an unlimited source of cells for clinical medicine and have begun to be used in clinical trials. Presently, although several hundred hESC lines are available in the word, only few have been widely used in basic and applied research. More and more hESC lines with differing genetic backgrounds are required for establishing a bank of hESCs. Here, we report the first Canadian hESC lines to be generated from cryopreserved embryos and we discuss how we navigated through the Canadian regulatory process. The cryopreserved human zygotes used in this study were cultured to the blastocyst stage, and used to isolate ICM via microsurgery. Unlike previous microsurgery methods, which use specialized glass or steel needles, our method conveniently uses syringe needles for the isolation of ICM and subsequent hESC lines. ICM were cultured on MEF feeders in medium containing FBS or serum replacer (SR). Resulting outgrowths were isolated, cut into several cell clumps, and transferred onto fresh feeders. After more than 30 passages, the two hESC lines established using this method exhibited normal morphology, karyotype, and growth rate. Moreover, they stained positively for a variety of pluripotency markers and could be differentiated both in vitro and in vivo. Both cell lines could be maintained under a variety of culture conditions, including xeno-free conditions we have previously described. We suggest that this microsurgical approach may be conducive to deriving xeno-free hESC lines when outgrown on xeno-free human foreskin fibroblast feeders.


Reduced TCOF1 mRNA level in a rhesus macaque with Treacher Collins-like syndrome: further evidence for haploinsufficiency of treacle as the cause of disease.
Mutations in the human gene TCOF1 cause a mandibulofacial dysostosis known as Treacher Collins syndrome (TCS). An infant rhesus macaque (Macaca mulatta) that displayed the TCS phenotype was identified at the California National Primate Research Center. The TCOF1 coding region was cloned from a normal rhesus macaque and sequenced. The rhesus macaque homolog of TCOF1 is 91.6% identical in cDNA sequence and 93.8% identical in translated protein sequence compared to human TCOF1. Sequencing of TCOF1 in the TCS-affected rhesus macaque showed no mutations within the coding region or splice sites; however, real-time quantitative PCR showed an 87% reduction of spleen TCOF1 mRNA level in the TCS affected macaque when compared with normal macaque spleen.


Synthesis of antimitotic analogs of the microtubule stabilizing sponge alkaloid ceratamine A.
Antimitotic analogs of the microtubule stabilizing sponge alkaloid ceratamine A (1) have been synthesized starting from tribromoimidazole. A key step in the synthesis is the formation of the azepine ring via an intramolecular Buchwald coupling between a vinyl bromide and a N-methyl amide. This represents the first synthesis of a fully unsaturated imidazo[4,5,d]azepine. NMR data obtained for the synthetic ceratamine analogs has provided support for the structure assigned to the natural product.


Ultrastructure of the paraphysis in Bufo bufo larvae.
A study of the ultrastructure and function of the paraphysis in Bufo bufo larvae was carried out. The structure is a tubular-ramified gland made up of numerous tubules with monolayered epithelial walls surrounded by connective tissue and sinusoids. The epithelial cells secrete glycoprotein to contribute to production of the cephalorachidian fluid. The role of the paraphysis in the transport of fluids and electrolytes from the blood to the cephalorachidian fluid in regulation of ionic and osmotic homeostasis is discussed.


Can pentoxifylline prevent renal disease?
The characteristics of pentoxifylline(Trental) suggest that it is an ideal agent to be used as adjunct in the therapy of chronic proliferative glomerulonephritides. Theoretical considerations suggest that pentoxifylline should also protect against and even ameliorate tubulo-interstitial fibrosis of affected kidneys.


Implanted islets in the anterior chamber of the eye are prone to autoimmune attack in a mouse model of diabetes.
Type 1 diabetes is an autoimmune disease resulting from the destruction of insulin-producing beta cells. Along with advances in generating replacement beta cells for treating diabetes, there is also increasing demand for non-invasive tools to evaluate the recurrence of autoimmune attack on transplanted tissue. Here, we examined the anterior chamber of the eye as a potential islet transplant site, and also evaluated whether in vivo imaging of the islets transplanted in the eye could enable real-time visualisation of autoimmune processes underway in the pancreas. Syngeneic islet equivalents were transplanted into the eye or kidney capsule of streptozotocin-induced diabetic C57BL/6 mice to compare islet dose (25-125 islet equivalents) and function across transplant sites. Autoimmune attack of syngeneic islets was evaluated in the pancreas and eye tissues of NOD and NOD-severe combined immunodeficient (SCID) mice given diabetogenic splenocytes. Islet transplantation in the eye decreased fasting plasma glucose levels and increased weight gain and survival in an islet-dose-dependent manner. Even 50 islets in the eye reduced blood glucose levels, whereas ≥ 200 islets were required in the kidney for a similar effect. Autoimmune destruction of pancreatic islets in the eye mirrored that in the pancreas and could be visualised in real time by non-invasive imaging. We found that far fewer islets were required to restore normoglycaemia when transplanted into the anterior chamber of the eye vs the kidney capsule. However, our results suggest that islets are not protected against autoimmune attack in the eye, making this a suitable site for visualising autoimmune processes against transplanted tissue.


Calcium influx pathways in rat CNS pericytes.
In central nervous system (CNS), pericytes have been proposed to play a role in broad functional activities including blood-brain barrier, microcirculation, and macrophage activity. However, contractile responses and Ca2+ signaling in CNS pericytes have not been elucidated. The aim of the present study is to investigate contractility and Ca2+ influx pathway in CNS pericytes. CNS pericytes were cultured from rat brain. Contraction of the pericytes in response to various stimuli was evaluated by the change in surface area measured by a light microscope with a digital camera. Reverse transcription and polymerase chain reaction (RT-PCR) was performed to examine the expression of mRNA of alpha-smooth muscle actin. Intracellular Ca2+ was measured using fura-2 fluorescence spectroscopy. A23187 (Ca2+ ionophore), high external K+ (4 x 10(-2) mol/l), endothelin-1, and serotonin induced contraction of CNS pericytes. RT-PCR analysis revealed the expression of alpha-smooth muscle actin in CNS pericytes. Cytosolic Ca2+ ([Ca2+]i) increased after application of high concentration of external K+, tetraethylammonium, and charybdotoxin, which was inhibited by nicardipine and removal of external Ca2+. Angiotensin-II, serotonin, acetylcholine, ATP, and endothelin-1 caused biphasic response in [Ca2+]i. In response to these agents, [Ca2+]i rapidly increased and then decayed to a relatively constant Ca2+ plateau. The Ca2+ plateau was partially inhibited by nicardipine and completely abolished by omission of external Ca2+. After intracellular Ca2+ store was depleted by the removal of external Ca2+ and addition of thapsigargin, reapplication of external Ca2+ evoked increases in [Ca2+]i. These results indicate that CNS pericytes express mRNA of alpha-smooth muscle actin and possess contractile ability. In CNS pericytes, resting membrane potential is regulated by large conductance Ca2+-activated K+ channels and Ca2+ enters into the cells via L-type voltage-dependent Ca2+ channels, agonist-activated Ca2+ permeable channels, and capacitative Ca2+ entry pathways.


Factors associated with severity of injury resulting from acute releases of hazardous substances in the manufacturing industry.
Data from the Hazardous Substances Emergency Events Surveillance system was used to identify factors associated with the severity of injuries of victims (an ordinal outcome variable) harmed in acute chemical release events in the manufacturing industry. We used proportional odds models to account for the order of severity in the outcome, with the general estimation equation. There were 659 events involving 2826 victims. More severe injuries were associated with explosion (adjusted OR aOR = 6.45), multiple chemicals (aOR = 1.75), multiple chemical categories (aOR = 1.70), the chemical group acids (aOR = 1.6), multiple injuries to an individual (aOR = 1.38-1.56) (ranges represent several models), confinement within a structure in a fixed facility (aOR = 1.76-1.90), and being located in the midwest region (aOR = 1.76-1.90). The summer was less likely than all other seasons to be associated with more severe outcome. The results provide information beneficial for preventive activities.


Diet models with linear goal programming: impact of achievement functions.
Diet models based on goal programming (GP) are valuable tools in designing diets that comply with nutritional, palatability and cost constraints. Results derived from GP models are usually very sensitive to the type of achievement function that is chosen.This paper aims to provide a methodological insight into several achievement functions. It describes the extended GP (EGP) achievement function, which enables the decision maker to use either a MinSum achievement function (which minimizes the sum of the unwanted deviations) or a MinMax achievement function (which minimizes the largest unwanted deviation), or a compromise between both. An additional advantage of EGP models is that from one set of data and weights multiple solutions can be obtained. We use small numerical examples to illustrate the 'mechanics' of achievement functions. Then, the EGP achievement function is demonstrated on a diet problem with 144 foods, 19 nutrients and several types of palatability constraints, in which the nutritional constraints are modeled with fuzzy sets. Choice of achievement function affects the results of diet models. MinSum achievement functions can give rise to solutions that are sensitive to weight changes, and that pile all unwanted deviations on a limited number of nutritional constraints. MinMax achievement functions spread the unwanted deviations as evenly as possible, but may create many (small) deviations. EGP comprises both types of achievement functions, as well as compromises between them. It can thus, from one data set, find a range of solutions with various properties.


Sound radiation from impact-driven raked piles.
Sound emissions from impact pile driving of raked piles present a significant azimuthal dependence in the radiated sound field due to the non-axisymmetric orientation of the pile. In this work the sound radiation from raked piles is modeled using a finite element method (FEM) model of the pile and near-field region. The near-field model of the sound field is then used as input into a normal mode model to predict the sound radiation in the far-field. The azimuthal dependence of the radiated sound field is shown to be accurately predicted using an equivalent axisymmetric FEM model of the pile configuration, thus negating the need to construct a fully three-dimensional model (3D) of the raked pile. This is achieved by matching the radiated field from the equivalent axisymmetric pile model to a vertical array of phased point sources, and then horizontally offsetting the source locations to match the incline of the raked pile. The resulting sound field closely matches the numerical predictions from a fully 3D FEM model of the raked pile. The results of numerical modeling are compared to corresponding acoustic measurements taken on the North West shelf of Western Australia.


Approximation of a foreign object using x-rays, reference photographs and 3D reconstruction techniques.
This case study describes how a 3D animation was created to approximate the depth and angle of a foreign object (metal bar) that had become embedded into a patient's head. A pre-operative CT scan was not available as the patient could not fit though the CT scanner, therefore a post surgical CT scan, x-ray and photographic images were used. A surface render was made of the skull and imported into Blender (a 3D animation application). The metal bar was not available, however images of a similar object that was retrieved from the scene by the ambulance crew were used to recreate a 3D model. The x-ray images were then imported into Blender and used as background images in order to align the skull reconstruction and metal bar at the correct depth/angle. A 3D animation was then created to fully illustrate the angle and depth of the iron bar in the skull.


Effect of lipids in milk replacers on calf performance and lipids in blood plasma, liver, and perirenal fat.
Various fats (20% of dry matter) were fed in milk replacer to calves, from 3 to 31 d of age, to compare their effect on calf performance, feed efficiency, and lipids in blood plasma, liver, and perirenal fat. Dietary fats tested were tallow (control), canola oil, canola soapstocks, corn oil, reclaimed restaurant cooking fat, and a high phospholipid waste product. Corn oil plus tallow (1:1) diet promoted scours and poor calf gains, but canola oil diet, despite a high content of unsaturated fatty acids, gave excellent calf performance and feed utilization and no scours. Canola soapstocks plus tallow (1:1) and restaurant waste cooking fat lowered gains by 25 and 15% and reduced diet intake. Calves effectively utilized high phospholipid (23%) in dietary lipids. Main lipid classes in blood plasma were cholesterol esters and phosphatidylcholine, and in liver phosphatidylethanolamine and phosphatidylcholine. Fatty acid composition of the major blood plasma and liver lipids, and of perirenal fat, tended to reflect dietary fatty acid concentrations.


Quality of life as an independent predictor for cardiac events and death in patients with heart failure.
Little is known about health-related quality of life (QOL) in Japanese patients with heart failure. The purpose of this study was to identify factors related to QOL using a disease-specific QOL instrument, and to clarify whether QOL independently predicts clinical outcomes among Japanese patients with heart failure. A total of 114 outpatients with heart failure were enrolled (mean age 64.7 ± 15.8 years; 73.7% males). The Minnesota Living with Heart Failure Questionnaire (MLHFQ) to assess patient's QOL was used. At baseline, depressive symptoms and chronic kidney disease were significantly associated with worse QOL in multiple regression analysis. During a 2-year follow up, patients with a MLHFQ score ≥ 26, indicating worse QOL, had a higher incidence of the combined endpoint of cardiac death or hospitalization for heart failure, and a higher all-cause mortality than those with a score < 26 (25.3% vs. 7.5%, P = 0.011; 18.5% vs. 6.4%, P = 0.018; respectively). Multivariate Cox proportional hazard models demonstrated that a higher MLHFQ score was significantly associated with increased risks of cardiac events (hazard ratio, 1.02, 95% confidential interval, 1.001-1.05, P = 0.038) and of all-cause death (hazard ratio, 1.04, 95% confidential interval, 1.02-1.07, P = 0.001). Depressive symptoms and chronic kidney disease are major determinants of impaired QOL, and the MLHFQ score is an independent predictor of both cardiac events and death among Japanese patients with heart failure.


Human liver and plasma aspirin esterase.
The plasma, in addition to the liver, is a major site of hydrolysis of aspirin. Human plasma and liver aspirin esterase activities in samples from a group of patients varied over a two fold range and there was a significant correlation between individual plasma and liver activities. Human liver aspirin esterase was present in the cytosolic and microsomal fractions. Cytosolic and microsomal enzymes had different activities and apparent affinities for aspirin.


Management of irradiated and contaminated casualty victims.
This article attempts to put into perspective the serious concerns regarding a radiation accident and to provide guidelines for the management of casualties arising from a radiation accident. It is intended primarily for the medical facility that does not have a specific requirement for a radiation accident treatment capability but wishes to be prepared should it be called upon to respond. A review of radiation effects is provided as well as guidelines for the management of irradiated or contaminated casualties. Psychological, public relations, and training concerns are also addressed.


Serum free levels and evaluation anticonvulsant drug interactions.
In clinical practice, serum level monitoring of anticonvulsant drugs is usually adequate. When there is an alteration in the binding of the anticonvulsant drug to the plasma proteins, however, the relationship between the serum concentration and therapeutic efficacy or toxicity becomes difficult to interpret. This can occur with combinations such as non-steroidal anti-inflammatory drugs (NSAIDs), phenytoin (Dilantin), carbamazepine (Tegretol), and valproic acid (Depakene) or when the albumin level is low. A failure to rely on serum free levels of the anti-convulsant under these circumstances can easily result in poor clinical decisions. The technique of serum free level measurement and illustrative examples of specific cases are provided to document the usefulness of this invaluable laboratory test.


Photolysis of an iodoplatinum(IV) diamine complex to cytotoxic species by visible light.
The feasibility of photolyzing the Pt(IV) complex trans,cis-[PtCl2I2(en)] to cytotoxic species by visible light was evaluated. The synthesis of trans, cis-[PtCl2I2(en)] was achieved by the oxidation of [PtI2(en)] with PCl5 in tetrahydrofuran at room temperature for 30 min in the dark. The UV-Vis spectrum of trans, cis-[PtCl2I2(en)] in water showed a broad ligand-to-metal charge-transfer (LMCT) band with lambda(max) = 396 nm (epsilon = 1191/M/cm). Although trans,cis-[PtCl2I2(en)] was relatively stable in water in the dark, irradiation at lambda(irr) = 410 nm brought about its rapid decomposition. A detailed analysis of the photodecomposition products was not carried out, but two lines of evidence suggest that I2 and [PtCl2(en)], a known antitumor agent, may be formed as a result of a reductive-elimination type reaction: (i) irradiation of trans, cis-[PtCl2I2(en)] in water at lambda(irr) = 410 nm led to the same spectral changes as when [PtCl2(en)] and I2 together were irradiated at the same wavelength; (ii) the photoinduced loss of trans,cis-[PtCl2I2(en)] was accompanied by the covalent binding of Pt to DNA at a rate comparable to that of [PtCl2(en)] at 37 degrees C, and the presence of 100 mM chloride suppressed this DNA platination. On the other hand, the combined photolysis products, formed when trans,cis-[PtCl2I2(en)] was irradiated in culture medium at lambda(irr) > 375 nm for 60 min, were less potent than [PtCl2(en)] at inhibiting the growth of two human cancer cell lines. Two limitations make the use of trans,cis-[PtCl2I2(en)] in the therapy of cancer impractical: (i) trans,cis- [PtCl2I2(en)] was relatively unstable in the presence of serum: however, [PtI2(en)] did not appear to be a product of the reaction; (ii) the LMCT band extends only weakly into the region of the electromagnetic spectrum (i.e. lambda > 600 nm) where maximal tissue penetration would be expected. In conclusion, these investigations demonstrate that iodo-Pt(IV) diamines can be photolyzed to cytotoxic species by visible light, but the aforementioned limitations must be overcome before this new class of Pt(IV) complexes can be used as antitumor agents.


Flow to a well in a five-layer system with application to the Oxnard Basin.
Nearly 40 years ago, Neuman (1968) developed an analytical solution for drawdown in a system of three aquifers separated by two aquitards when one of the aquifers is pumped at a constant rate. Whereas the simpler case of two aquifers separated by one aquitard has been presented by Neuman and Witherspoon (1969a), the full five-layer solution has not been previously evaluated. We do so here using numerical inversion of its Laplace-transformed version and present selected results graphically in dimensionless form. The solution demonstrates that the effect of pumping propagates across all five layers, adding emphasis to a question previously raised by Neuman and Witherspoon about the validity of leaky aquifer theories that disregard drawdowns in unpumped aquifers. A large-scale, long-term pumping test spanning three aquifers separated by two aquitards near Oxnard, California, has been conducted and analyzed by Neuman and Witherspoon (1972). They evaluated the vertical hydraulic diffusivities of the aquitards using the Neuman-Witherspoon ratio method and their specific storage values on the basis of laboratory consolidation tests. We reinterpret the Oxnard pumping test by coupling the five-layer analytical solution of Neuman (1968) with the parameter estimation code PEST (Doherty 2002) and validate our results against drawdowns from a subsequent pumping test at the site. Our parameter estimates compare favorably with those of Neuman and Witherspoon (1972).


A DNA-binding protein defines the precise region of chromosome capture during Bacillus sporulation.
During sporulation, Bacillus subtilis divides around the nucleoid near one cell pole, initially capturing approximately one quarter of one chromosome in the newly formed forespore compartment. While it is known that a specific region of the nucleoid is reproducibly captured in the forespore, the mechanism underlying the precision of capture is unknown. Here we describe a role for RefZ, a DNA-binding protein that regulates FtsZ, and its cognate binding motifs (RBMs) in defining the specific region of chromosome initially captured in the forespore. RefZ is conserved across the Bacillus genus and remains functional as an inhibitor of cell division in a species-swapping experiment. The RBMs are also conserved in their positioning relative to oriC across Bacillus, suggesting that the function of the RBMs is both important and position-dependent in the genus. In B. subtilis, the RBMs flank the region of the chromosome captured at the time of cell division, and we find that RefZ binds the five oriC-proximal RBMs with similar apparent affinity in units of two and four. refZ and RBM mutants capture chromosomal regions normally excluded from the forespore, suggesting that RefZ-RBM complexes play a role in regulating the position of cell division relative to the chromosome during sporulation.


Receptive field mechanism in the vertebrate retina.
In the catfish retina there are two types of ganglion cells: in one type (type A cell) a spot of light at the center of its receptive field gives rise to a sustained discharge whereas an annulus gives rise to a transient response, and in the other type (type B cell) the response pattern is reversed for a spot and an annulus. Current injected into the horizontal cell induces spike discharges of the ganglion cell very similar to that elicited by a spot of light or by an annulus. In both types of receptive fields, depolarization of the horizontal cell gives rise to a response of the ganglion cell similar to that elicited by a spot of light, whereas hyperpolarization of the cell gives rise to a response of the ganglion cell similar to that elicited by an annulus. Current through a single injecting electrode could drive two types of cells simultaneously. Interaction between a spot of light and an annulus can also be simulated by replacing one light stimulus by current of the proper polarization injected into the horizontal cells. Results suggest that interactions among three neuronal structures, the receptor, the horizontal cell, and the bipolar cell, produce the basic receptive field organization in the channel catfish.


Toward the discovery and development of effective modulators of α-synuclein amyloid aggregation.
A host of human diseases, including Parkinson's disease and Dementia with Lewy bodies, are suspected to be directly linked to protein aggregation. Amyloid protein aggregates and oligomeric intermediates of α-synuclein are observed in synucleinopathies and considered to be mediators of cellular toxicity. Hence, α-synuclein has seen as one of the leading and most compelling targets and is receiving a great deal of attention from researchers. Nevertheless, there is no neuroprotective approach directed toward Parkinson's disease or other synucleinopathies so far. In this review, we summarize the available data concerning inhibitors of α-synuclein aggregation and their advancing towards clinical use. The compounds are grouped according to their chemical structures, providing respective insights into their mechanism of action, pharmacology, and pharmacokinetics. Overall, shared structure-activity elements are emerging, as well as specific binding modes related to the ability of the modulators to establish hydrophobic and hydrogen bonds interactions with the protein. Some molecules with encouraging in vivo data support the possibility of translation to the clinic.


Histopathology of the endoscopic esophagogastric junction in patients with gastroesophageal reflux disease.
Discrepancy exists between the endoscopic (rugal folds) and the histopathologic (oxyntic mucosa) definition of proximal stomach. We compared endoscopy and histopathology of the esophagogastric junction in patients with gastroesophageal reflux disease. A total of 102 consecutive patients (60 women) with gastroesophageal reflux disease prospectively underwent endoscopy including multilevel biopsy sampling at the level of the rise of rugal folds (level 0), and also 0.5 cm and 1.0 cm distal and 0.5 cm and > or = 1 cm proximal to this point. Columnar lined esophagus (CLE) was cataloged according to the histopathologic Paull-Chandrasoma classification and esophagitis according to the endoscopic Los Angeles classification. Hiatal hernia was diagnosed if the endoscopic rugal folds commenced > or = 2 cm above the diaphragm; competency of the esophagogastric valve was graded according to the Hill classification. All patients had histopathologic CLE with maximal presence at level 0 (97%) and a decrease towards proximal and distal biopsy levels (level -0.5 cm, 81%; level -1.0, 28%; level + 0.5 cm, 40%; level + 1.0 cm, 18%). Histopathologic CLE (distance between CLE-positive biopsy levels) was longer than endoscopic CLE (P < 0.001). All 19 patients with intestinal metaplasia (18.6%) were identified from 4-quadrant biopsies obtained at the squamocolumnar junction and at 0.5 cm distal from it. Persons with intestinal metaplasia were significantly older, had increased frequency of endoscopic hiatal hernia, higher Hill grade and presence of endoscopic CLE (P < 0.05); no significant difference was observed regarding sex, endoscopic esophagitis or length of endoscopic and histopathologic CLE (P > 0.05). None of the patients had dysplasia or carcinoma. In patients with gastroesophageal reflux disease the esophagogastric junction cannot be identified by endoscopy but requires histopathology of multilevel biopsies. The squamocolumnar junction harbors the highest yield of intestinal metaplasia.


Genetic modulation of ethylene biosynthesis and signaling in plants.
With the isolation and characterization of the key enzymes and proteins, and the corresponding genes, involved in ethylene biosynthesis and sensing it has become possible to manipulate plant ethylene levels and thereby alter a wide range of physiological processes. The phytohormone ethylene is an essential signaling molecule that affects a large number of physiological processes; plants deprived of ethylene do not grow and develop normally. In a search for flexible on-off ethylene control, scientists have used inducible organ- and tissue-specific promoters to drive expression of different transgenes. Here, the various strategies that have been used to genetically engineer plants with decreased ethylene biosynthesis and sensitivity are reviewed and discussed.


[Several approaches to purifying rat liver G2-chalone].
An attempt was made to isolate the liver tissue chalone blocking the transition of hepatocytes from G2 period of the cell cycle into mitosis/g2-chalone/. The purification was carried out using gel filtration through Sephadex G-75 and hydroxyapatite chromatography as well as by means of ultrafiltration through Diaflo membranes XM-300, XM-100 and PM-10. The biologically active preparation, obtained by these two procedures, was purified 100-fold. Molecular mass of G2 chalone was apparently less then 10,000; it penetrated through PM-10 membrane. The chalone appears to form complexes with high molecular carriers.


Psychologic and psychophysiologic response to 105 days of social isolation.
The responses of nine subjects to 105 d of social isolation are reported. The study reveals that crew selection plus ongoing support by psychiatric staff permits continued function in an exotic milieu. Prediction of psychophysiologic symptoms was possible using paper and pencil tests. Trait anxiety was altered by the isolation in a psychologically healthy direction. Sudden time shifts of 8 h led to an immediate significant increase in depression, aggression, and hostility, and are accompanied by marked increases in physical symptoms. During the first free-running phase of the experiment, significant shifts were found on four psychological measures. The shifts indicate that subjects became less trusting, more orderly, more routinized, less energetic, and more depressed. A reducer-augmenter scale predicted the number of psychophysiologic complaints reported by individual subjects while isolated. A group interaction effect on circadian rhythms was isolated but needs further examination.


Enhancing Membrane Protein Identification Using a Simplified Centrifugation and Detergent-Based Membrane Extraction Approach.
Membrane proteins may act as transporters, receptors, enzymes, and adhesion-anchors, accounting for nearly 70% of pharmaceutical drug targets. Difficulties in efficient enrichment, extraction, and solubilization still exist because of their relatively low abundance and poor solubility. A simplified membrane protein extraction approach with advantages of user-friendly sample processing procedures, good repeatability and significant effectiveness was developed in the current research for enhancing enrichment and identification of membrane proteins. This approach combining centrifugation and detergent along with LC-MS/MS successfully identified higher proportion of membrane proteins, integral proteins and transmembrane proteins in membrane fraction (76.6%, 48.1%, and 40.6%) than in total cell lysate (41.6%, 16.4%, and 13.5%), respectively. Moreover, our method tended to capture membrane proteins with high degree of hydrophobicity and number of transmembrane domains as 486 out of 2106 (23.0%) had GRAVY > 0 in membrane fraction, 488 out of 2106 (23.1%) had TMs ≥ 2. It also provided for improved identification of membrane proteins as more than 60.6% of the commonly identified membrane proteins in two cell samples were better identified in membrane fraction with higher sequence coverage. Data are available via ProteomeXchange with identifier PXD008456.


Effects of television content on physical risk-taking in children.
This study is an investigation of effects of risk-taking by characters in television programs on children's self-reported willingness to take physical risks. Twenty-four boys and 26 girls, ages 6 to 9 years, were assigned to view TV stimulus programs with infrequent physical risk-taking. TV stimulus programs with frequent risk-taking, or no TV stimuli. A self-report measure was used to assess children's willingness to take physical risks in several common injury-relevant situations. Five of the items were administered as a pretest before children watched the stimulus programs and five items were used as a post-test after they viewed the programs. A validation assessment on an independent sample of children indicated that the risk-taking measure was positively correlated with other measures of risk-taking as well as physical injuries. Results indicated that children who viewed the high-risk TV programs increased their self-reported risk-taking significantly more than children in the low-risk TV and no-TV control conditions. Findings are discussed within a theoretical context of observational learning processes, with implications for childhood injury.


Nitric oxide is a regulator of bone remodelling.
Nitric oxide (NO) is known to be implicated in the metabolism of bone, especially as a mediator of cytokine effects on the remodelling of bone tissue. In this study we examine whether NO affects the osteoblast activation or the osteoclast differentiation of primary mouse osteoblast-like and osteosarcoma ROS 17/2.8 cell lines. Primary osteoblast and ROS 17/2.8 cells released NO upon stimulation of interleukin-1 beta, tumour necrosis factor-alpha, and interferon-gamma. Sodium nitroprusside, a donor of nitric oxide, increased the activity of alkaline phosphatase in ROS 17/2.8 cells as well as the number of calcified nodule formations in primary mouse osteoblast-like cells. Sodium nitroprusside also completely inhibited 1 alpha, 25-(OH)2D3-induced osteoclast generation in a high concentration (100 microM). However, a low concentration of sodium nitroprusside (3-30 microM) significantly increased the generation of osteoclasts. These results indicated that NO appears to be an important regulatory molecule in the processes of bone formation and resorption. Hence, NO may be involved in the pathogenesis of bone loss in diseases associated with cytokine activation, such as periodontal disease and rheumatoid arthritis.


Fibronectin and proteolytic fragments of fibronectin interfere with the adhesion of Staphylococcus epidermidis to plastic.
The adhesion of five strains of slime-positive Staphylococcus epidermidis to plastic microwells was significantly diminished (P < 0.005) in a concentration-dependent fashion when wells were previously coated with increasing concentrations (1.6-13.1 micrograms cm-2) of human fibronectin (FN). The adhesion of four of five strains was significantly reduced when wells were coated with 3.2 micrograms cm-2 of FN and at concentrations > or = 6.5 micrograms cm-2 the adhesion of all slime-positive strains was significantly reduced. The coating of microwells with chymotryptic fragments of FN containing the heparin-binding, gelatin-binding, or cell-binding domains also reduced bacterial adhesion but none of the fragments exceeded the anti-adhesive activity of intact FN. A comparison of FN-coated or albumin-coated microwells showed that both proteins caused a significant reduction in the adhesion of test strains to plastic but that the anti-adhesive activity of FN was greater than albumin at all concentrations tested. The adhesion of the slime-negative phase variant of one of the test strains to plastic was neither enhanced nor reduced by FN coating indicating that the production of an exopolysaccharide by Staph. epidermidis influences interactions with protein-coated surfaces. These results support the contention that FN does not mediate the adhesion of all strains of Staph. epidermidis to plastic surfaces.


Sibling conflict in middle childhood predicts children's adjustment in early adolescence.
Associations between sibling conflict in middle childhood and psychological adjustment in early adolescence were studied in a sample of 80 boys and 56 girls. Parents and children provided self-report data about family relationships and children's adjustment. Parents' hostility to children was assessed from videotaped interactions. Results showed that sibling conflict at Time 1 predicted increases in children's anxiety, depressed mood, and delinquent behavior 2 years later. Moreover, earlier sibling conflict at Time 1 accounted for unique variance in young adolescents' Time 2 anxiety, depressed mood, and delinquent behavior above and beyond the variance explained by earlier maternal hostility and marital conflict. Children's adjustment at Time 1 did not predict sibling conflict at Time 2. Results highlight the unique significance of the earlier sibling relationship for young adolescents' psychological adjustment.


Laparoscopic redo paraesophageal hernia repair with collis gastroplasty for shortened esophagus.
Esophageal shortening can be seen in patients with chronic inflammation associated with gastroesophageal reflux disease and paraesophageal hernias. During surgical treatment of these conditions, it is important to address the esophageal shortening during the operation for optimal outcomes. Ideally, 2.5-3 cm of tension-free intraabdominal esophagus is recommended. During this video, we show a redo paraesophageal hernia repair in which we were unable to achieve adequate esophageal lengthening despite extensive mediastinal dissection. We therefore proceeded with Collis gastroplasty with Toupet fundoplication.


[The complications of nerve injury after the Le Fort I osteotomy].
To investigate the incidence of the temporary and permanent sensory disturbance of the inferorbital nerve (ION) after Le Fort I osteotomy. Thirty patients with 60 inferorbital nerves were examined preoperatively, 1 week, 1 month, 3 months and 6-months after the operation of the Le Fort I osteotomy by using sharp-blunt testing, 2-point discrimination, electric pain response test (ZGK-1 electrometer). The incidence of the temporary nerve impairment was 75% (45 of 60) and the obvious recovery was found after 1 to 3 months after the operation. No permanent sensory disturbance was found in the patients. The inferorbital nerve injury after Le Fort I osteotomy is usually temporary and the sensory recovery was in 1 to 3 months after the operation.


[Effect of Electroacupuncture Intervention on Rehabilitation of Upper Limb Motor Function in Patients with Ischemic Stroke].
To observe the effect of electro-elongated needle intervention on rehabilitation of upper limb motor function in patients with ischemic stroke. A total of 100 ischemic stroke patients were equally and randomly divided into manual acupuncture group and electro-elongated needle group (n=50 cases/group). For patients of the manual acupuncture group, filiform needles were respectively inserted into Jianyu (LI 15), Jiquan (HT 1), Shousanli (LI 10), Neiguan (PC 6) and Hegu (LI 4) on the affected side, manipulated with lifting-thrusting reinforcing or reducing method for 40 min, once daily for two weeks except the weekends, and for those of the electro-elongated needle group, elongated needles were repeatedly penetrated from LI 15 to Binao (LI 14), and from LI 10 to Waiguan (TE 5) on the affected side, followed by electrical stimulation for 40 min, once daily for two weeks except weekends. The therapeutic effect of manual acupuncture and electro-elongated needle for upper extremity rehabilitation was assessed according to the modified upper-extremity Fugl-Meyer Assessment (FMA) and Wolf Motor Function Test (WMFT) separately. The surface electromyogram (sEMG) of the deltoid muscle was recorded by using a Megawin Surface Electrogram System and the root mean square (RMS) of the amplitude of sEMG was used to evaluate the functional state of the deltoid muscle. After the treatment, the score of FMA and WMFT in both manual acupuncture and electro-elongated needle groups were significantly increased compared with pre-treatment in the same one group (P<0.01), suggesting an improvement of the motor function of the upper limbs, but RMS ratios of the amplitude of sEMG were evidently decreased in both groups (P<0.05, P<0.01), suggesting a relief of the abnormal muscular tension. The therapeutic effects of the electro-elongated needle were obviously superior to those of manual acupuncture in up-regulating FMA and WMFT scores and down-regulating RMS ratio (P<0.01). Electro-elongated needle therapy can effectively improve the motor function of upper limb in ischemic stroke patients and has a better effect in comparison with simple manual acupuncture.


Herbivorous snails can increase water clarity by stimulating growth of benthic algae.
Eutrophication in shallow lakes is characterized by a switch from benthic to pelagic dominance of primary productivity that leads to turbid water, while benthification is characterized by a shift in primary production from the pelagic zone to the benthos associated with clear water. A 12-week mesocosm experiment tested the hypothesis that the herbivorous snail Bellamya aeruginosa stimulates the growth of pelagic algae through grazing on benthic algae and through accelerating nutrient release from sediment. A tube-microcosm experiment using 32P-PO4 as a tracer tested the effects of the snails on the release of sediment phosphorus (P). The mesocosm experiment recorded greater total nitrogen (TN) concentrations and a higher ratio of TN:TP in the overlying water, and a higher light intensity and biomass of benthic algae as measured by chlorophyll a (Chl a) in the snail treatment than in the control. Concentrations of total phosphorus (TP), total suspended solids (TSSs), and inorganic suspended solids (ISSs) in the overlying water were lower in the snail treatment than in the control, though no significant difference in Chl a of pelagic algae between the snail treatment and control was observed. In the microcosm experiment, 32P activity in the overlying water was higher in the snail treatment than in the control, indicating that snails accelerated P release from the sediment. Our interpretation of these results is that snails enhanced growth of benthic algae and thereby improved water clarity despite grazing on the benthic algae and enhancing P release from the sediment. The rehabilitation of native snail populations may therefore enhance the recovery of eutrophic shallow lakes to a clear water state by stimulating growth of benthic algae.


Activation of liver X receptor protects inner retinal damage induced by N-methyl-D-aspartate.
To investigate whether activation of liver X receptors (LXRs) protects N-methyl-D-aspartic (NMDA)-induced retinal neurotoxicity in mice and to explore the underlying mechanism. Inner retinal damage was induced by intravitreal injection of NMDA. A synthetic LXR ligand TO901317 (TO90, 50 mg/kg/d) or vehicle was intragastrically administrated from 3 days before to 1 day or 7 days after NMDA injection. The severity of retinal damage was evaluated with histological analysis and TUNEL staining, and retinal functions were evaluated by ERG. The expressions of caspase-3, bax, bcl-2, TNF-α, and BACE1, the rate-limiting enzyme in the formation of amyloid β (Aβ), in the retina were examined by real-time PCR and ELISA. The levels of LXRs, NF-κB subunit p65, p-p38 mitogen-activated protein kinase (MAPK), and an LXR target gene ABCA1 were detected with real-time PCR and Western blotting. The localization and protein expression of Aβ in the retina was assessed by immunohistochemistry and Western blotting. The NMDA enhanced the expression of LXRβ but not LXRα and ABCA1 in mouse retina. Nevertheless, administration of TO90 after NMDA injection not only enhanced the expression of LXRβ but also upregulated the level of ABCA1, suggesting retinal LXRs were activated in a ligand-dependent manner. The LXRα expression was unchanged in the vehicle and the TO90-treated groups. Activation of LXRβ with TO90 inhibited cell death in the ganglion cell layer (GCL) and inner nuclear layer (INL), preserved ERG b- and a-wave amplitudes, and the b/a ratio in the NMDA-treated mice. Meanwhile, TO90 suppressed the elevation of apoptosis factors caspase-3 and bax induced by NMDA and upregulated the level of an antiapoptotic factor bcl-2. The TO90 also inhibited the increase of p-p38 MAPK and proinflammatory cytokine TNF-α after NMDA injection. Furthermore, activation of LXR attenuated the activation of NF-κB, and reduced gene expression of BACE1 and accumulation of Aβ induced by NMDA. Activation of LXRβ with a synthetic LXR ligand TO90 protects the inner retinal damage induced by NMDA in mice. We speculate the protective effect is associated with inhibition of the NF-κB signaling pathway and reduction of Aβ formation in retina. The LXR agonists may become a new class of neuroprotective agent for retinal diseases associated with glutamate-induced excitotoxicity.


Reduced expression of sialoglycoconjugates in the outer hair cell glycocalyx after systemic aminoglycoside administration.
In this study we investigated the effect of systemic aminoglycoside administration on the expression of sialoglycoconjugates in the outer hair cell (OHC) glycocalyx of the adult guinea pig. Sialoglycoconjugates were visualized by means of ultrastructural lectin cytochemistry, using Limax flavus agglutinin (LFA) and wheat germ agglutinin (WGA) as probes. Labelling densities were determined for the apical membranes (including the stereocilia and stereociliary cross-links) and basolateral membranes of OHCs in the respective (basal, middle and apical) cochlear turns from animals that had been treated with gentamicin or neomycin for 5 or 15 consecutive days. Our results indicate that: (1) sialoglycoconjugate expression in the OHC glycocalyx demonstrates an intracochlear gradient decreasing towards the apical turn; (2) OHCs demonstrate a polarity in sialoglycoconjugate expression, in that the basolateral membranes contain more sialoglycoconjugates per surface area than the apical membranes; (3) aminoglycoside administration results in reduced expression of sialoglycoconjugates in the OHC glycocalyx; in this respect, basal-turn OHCs are more susceptible than those in the middle and apical turns; (4) reduction in sialoglycoconjugate expression after aminoglycoside administration is more prominent in the basolateral membranes; and (5) the difference in ototoxic potencies between gentamicin and neomycin is not reflected at the level of sialoglycoconjugate expression. The present data support our earlier hypothesis that aminoglycosides, already at an early phase of intoxication, interfere with the function of the endoplasmic reticulum and/or the Golgi apparatus, implying that these organelles play a crucial role in the initial phase of aminoglycoside-induced OHC degeneration.


[Preparation and luminescence properties of transparent Gd2O3 : Eu thick film].
High-resolution X-ray imaging systems require materials with good scintillation performances, especially X-ray absorption performance. Compared with powder phosphors display devices, those with transparent crystalline phosphors are very interesting due to their higher contrast and resolution for having no optical scattering, superior thermal conductivity as well as high degree of uniformity and better adhesion. Europium-doped gadolinlum oxide is a promising candidate due to its high density (7.62 g x cm(-3)), good light yield (18.5 x 10(3) photons/MeV), and the red emission of Eu3+ ion. The sol-gel method is one of the most important techniques for deposition of functional films, because it possesses a number of advantages over conventional film formation techniques, such as low processing temperature, easy coating of large surfaces, and homogenous multicomponent oxide films. In X-ray imaging application, the thickness of the film is the most important factor for commercial use, which can increase X-ray absorption of the film and then strengthen its luminescence yield. In the present work, transparent Gd2 O3 : Eu3+ thick film was successfully prepared using sol-gel method and spin-coating technique by choosing Ln2 O3 (Ln = Gd, Eu) as raw materials, 2-methoxyethanol as solvent, PVP as adhesive and PEG200 as surface modifier. The film was homogeneous and crack free. The thickness of the film could achieve 1.5 microm after 2 times of coating, and its transmittance was approximately 80% in visible region. It was shown that PVP played an important role in film preparation, which could suppress stress and increase viscidity of the sol. In addition, the excitation, emission and decay time of the Gd2 O3 : Eu3+ scintillator film were studied. Their performances were quite good, which implied that the film would have promising applications in high-spatial-resolution X-ray imaging and flat panel display devices.


Steric, electronic, and secondary effects on the coordination chemistry of ionic phosphine ligands and the catalytic behavior of their metal complexes.
The effects of introducing ionic functionalities in phosphine ligands on the coordination chemistry of these ligands and the catalytic behavior of the corresponding metal complexes are reviewed. The steric and electronic consequences of such functionalizations are discussed. Apart from these steric and electronic effects, the presence of charged groups often leads to additional, supramolecular interactions that occur in the second coordination sphere of the metal complex, such as intramolecular, interligand hydrogen bonding and Coulombic repulsion. These interactions can significantly alter the behavior of the phosphine ligand in question. Such effects have been observed in phosphine-metal association/dissociation equilibria, ligand substitution reactions, and stereoisomerism in phosphine-metal complexes. By drawing general conclusions, this review offers an insight into the coordination and catalytic behavior of phosphine ligands containing ionic functionalities and their corresponding metal complexes.


[The mechanism of carbofuran interacts with calf thymus DNA].
Carbofuran is an insecticide used on a variety of corps. Acute and chronic occupational exposure of humans to carbofuran has been observed to cause cholinesterase inhibition, but little is known about the interaction of carbofuran with DNA. Using the technique of UV spectrum and fluorescence quenching respectively, the interaction between carbofuran and ct DNA was studied. The UV spectrum showed that ct DNA can lead to the hypochromic effect and red shift of the UV spectrum of carbofuran. The quenching process was proved to be the single static quenching and quenching constant decreases with temperature increasing. The basis of this specificity is intercalation of insecticide between base pairs to produce ct DNA-carbofuran adducts. Furthermore, ethanol can produce Franck-condon effect on the ct DNA-carbofuran adducts. At different sodium chloride concentrations, quenching constant had no significant change, which appeared that there was little electrostatic interaction between ct DNA and carbofuran and it was intercalation.


Benefits and costs of MR imaging of prostate cancer.
This article answers several important questions about the ultimate clinical usefulness of prostate MR imaging. How accurate is prostate MR imaging? What are the optimal methods for performance and interpretation of the study, considering the tradeoffs between false-positive and false-negative results? Is endorectal-coil imaging a cost-effective part of the prostate examination? And, which men are likely to benefit the most from an endorectal prostate examination?


Coronary prevention and regression studies updated.
There have been a multitude of clinical, animal and epidemiology studies which prove that high serum cholesterol and low density lipoprotein (LDL) cholesterol concentrations are specific causes of coronary artery disease (CAD). Although the variations in experimental design make comparisons difficult, the aggregate results of many human prevention trials since 1960 lead to the definite conclusion that a 10% lowering of serum cholesterol reduces the risk of CAD by one-sixth. Recently, other factors for CAD risk have been identified that will be useful in guiding treatment, namely serum high density lipoprotein (HDL) cholesterol, apolipoproteins B and AI, HDL triglycerides and phosphatidylcholine to free cholesterol ratio. Studies have shown that aggressive drug and diet therapy slows progression and causes regression of atheromas. Primary prevention of CAD is obviously preferable to secondary prevention. Also, the evidence to date indicates that prevention of CAD through lifestyle changes should begin in childhood.


Thyroid-stimulating hormone (TSH) is associated with 30-day mortality in hip fracture patients.
The aim of this study is to assess the possible association between thyroid-stimulating hormone (TSH) and mortality in hip fracture patients. The study is based on a hip fracture database from Bispebjerg University Hospital (Copenhagen, Denmark). This database includes all hip fracture patients (ICD-10 codes DS720 (femoral neck), DS721 (pertrochanteric), and DS722 (subtrochanteric)) admitted to Bispebjerg Hospital from 1996 to 2012. From this database, we identified all surgically treated hip fracture patients aged > 60 years with available plasma TSH-measurements at admission. Of the 914 included patients (24% men and 76% women), 10.5% died within 30 days. At inclusion, 161 (17.6%) of the patients were hyperthyroid (TSH < 0.65 mIU/L), 58 (6.4%) were hypothyroid (TSH > 4.8 mIU/L), while 695 (76.0%) were euthyroid (0.65 < TSH < 4.80 mIU/L), p = 0.03. Mortality was significantly higher in the two higher quartiles of TSH [Q3 (13.0%) and Q4 (15.4%)] compared to the two lower quartiles [Q1 (7.4%) and Q2 (6.2%), p = 0.0003. After adjustment for age, sex and Charlson Comorbidity Index (CCI) in a Cox proportional hazard model, the risk of 30-day mortality continued to be increased in patients with TSH above the median as compared to patients with TSH below the median (HR 2.1 (1.4-3.3), p = 0.0006]. The study demonstrates increased 30-day mortality in surgically treated hip fracture patients with plasma TSH levels above the median (1.41 mIU/L) at admission, even after adjusting for age, sex and CCI.


The health benefits following regular ongoing exercise lifestyle in independent community-dwelling older Taiwanese adults.
To examine the effect of regular ongoing exercise lifestyle on mental and physical health in a group of independent community-dwelling Taiwanese older adults over a 2-year period. 197 older adults (mean age 72.5 years; 106 men and 91 women) who were independent in walking, instrumental and basic activities of daily living completed the baseline and a 2-year follow-up assessment. Older adults regularly performing exercises during the 2-year study period were grouped into regular exercise group; otherwise in the irregular exercise group. Baseline and follow-up assessments included a face-to-face interview and a battery of performance tests. The regular exercise group showed significantly less depression (P = 0.03) and tended to regress less on the performance tests (P = 0.025-0.410) across 2 years compared to the irregular exercise group. Regular exercise is important for maintaining or even improving mental and functional health, even for independent community-dwelling older adults.


Influence of growth hormone on bone marrow adipogenesis in hypophysectomized rats.
The hypophysectomized rat has been used as a model to study the effects of growth hormone deficiency on bone. Here, we have investigated the influence of growth hormone administration to hypophysectomized rats (HX) for 6 wk on accumulation of triglycerides in bone marrow and on the differentiation of primary marrow stromal cells into adipocytes under in vitro conditions. We found that hypophysectomy significantly increased triglyceride concentration in bone marrow, which was attenuated by growth hormone administration. Primary bone marrow stromal cells derived from HX rats also had more adipocytes at confluence compared with growth hormone-treated hypophysectomized (GH) rats. When stimulated with 3-isobutyl-1-methylxanthine plus dexamethasone (IBMX-Dex), preadipocyte colony counts increased more significantly in GH rats. Markers of adipocyte differentiation were higher in HX than in control or GH rats at confluence. However, after stimulation with IBMX-Dex, increased expression of markers was seen in GH compared with HX rats. In conclusion, growth hormone administration to hypophysectomized rats attenuated triglyceride accumulation in bone marrow and inhibited the differentiation of stromal cells into adipocytes in vitro.


Laryngotracheoesophageal cleft. An easily missed malformation.
Laryngotracheoesophageal cleft is a rare congenital anomaly characterized by a midline defect of variable length between the posterior larynx and trachea and the anterior wall of the esophagus. This report concerns the clinical course and follow-up of three patients with this anomaly and a review of the literature. Only one of these patients had a successful repair on the first attempt. The difficulty in making the diagnosis is stressed. This anomaly is associated with a high morbidity and mortality.


[Effect of successive cyclic administration of oleandomycin and tetracycline on the immunogenic reactivity and indices of non-specific bodily resistance in experimental staphylococcal sepsis].
The effect of subsequent cyclic administration of oleandomycin and tetracycline on the titer of the complement, the content of lysozyme, the bactericidal properties of the serum and the presence of the antibiotic specific antibodies in the blood serum found in the Hoigne reaction were studied on rabbits. It was found that the subsequent cyclic administration of the antibiotics to both the intact animals and the animals with experimental staphylococcal sepsis was accompanied by an increase in the titer of the complement only on the 7th day of administration of oleandomycin, the first antibiotic. The subsequent administration of tetracycline and especially discontinuation of the antibiotics use resulted in a significant, stable and prolonged decrease in the complement titer. The cyclic subsequent administration of oleandomycin and tetracycline for 7 days was accompanied by an increase in the lysozyme content and serum bactericidal properties. Changes in the factors of non-specific resistance under the effect of the subsequent cyclic administration of oleandomycin and tetracycline on both the intact animals and the animals with experimental staphylococcal sepsis were accompanied by an appearance, progressive increase and prolonged preservation in the serum of the antibiotic specific antibodies found in the Hoigne reaction. A possibility of producing specific antibodies simultaneously to the 2 antibiotics, i. e. oleandomycin and tetracycline in their administration in subsequent 7-day cycles was shown.


Efficacy of chlorine dioxide gas against Alicyclobacillus acidoterrestris spores on apple surfaces.
Alicyclobacillus acidoterrestris is a thermophilic spore-forming bacterium that spoils acidic juices. In the orchard, apples may be contaminated with spores which can potentially grow in the resulting juice and cause spoilage. This study was undertaken to evaluate the efficacy of gaseous chlorine dioxide against A. acidoterrestris spores on apple surfaces. A. acidoterrestris spores were inoculated onto apple surfaces and were placed at room temperature, in a tightly sealed chamber containing a chlorine dioxide generating sachet, low, medium, or high release, for 30 min, 1, 2, and 3 h. After exposure, surviving spores were enumerated on K agar. Chlorine dioxide treated apples were stored at 4 degrees C for 7 days to assess the effect on visual quality. Inoculated, untreated apples served as the visual quality control. After exposure to high and medium release sachets for 1 h, spores were reduced to an undetectable level, a 5 log10 reduction; however, visual quality was compromised. After 1, 2, and 3 h of exposure to low release sachets, spore reductions were 2.7, 3.7, and 4.5 log10, respectively. And, after 7 days of storage, there were no significant visual quality differences between the apples exposed to low release sachet for all treatment times when compared to the control. Gaseous chlorine dioxide can effectively reduce viable A. acidoterrestris spores on apple surfaces. Due to the efficacy and easy of use, chlorine dioxide gas sachets may be useful to maintain apple quality during storage and shipping.


Effect of shortening replacement with oleogels on the rheological and tomographic characteristics of aerated baked goods.
A great deal of effort has been made to reduce the use of shortening owing to the high level of saturated fats as well as the presence of trans fats. Grape seed oil high in unsaturated fats was structured with candelilla wax to form solid-like oleogels that were utilized as a shortening replacer in aerated baked goods, specifically muffins. Muffin batters with greater amounts of oleogels exhibited lower viscosity, greater shear-thinning behavior and less elastic nature. The shortening replacement with oleogels significantly increased the specific gravity of the batters, consequently affecting the muffin volume after baking. X-ray tomography indicated a lower fragmentation index (i.e. a more connected solid structure) in the oleogel-incorporated muffins, which was correlated with more enclosed and isolated air cells. A stress relaxation test showed that the shortening replacement with oleogels produced muffins with a firmer and springier texture. Based on fatty acid compositions, the ratio of saturated to unsaturated fatty acids was significantly reduced from 2.81 to 0.41. Use of the oleogels as a shortening replacer at a ratio of 1:3 by weight was effective in producing muffins with comparable quality attributes to the control with shortening. © 2017 Society of Chemical Industry.


Membrane connexin 43 acts as an independent prognostic marker in oral squamous cell carcinoma.
The aim of the present study was to evaluate the expression and localization of connexin (Cx) 26, -43 and -45 in a group of 35 patients with primary oral squamous cell carcinoma (OSCC) with the objective of making a more accurate disease prognosis. We analysed the expression of connexins in tissue samples of primary OSCC, matching oral mucosa free of dysplasia, and its associated lymph node metastases (LNM) by semi-quantitative immunohistochemistry of membrane, cytoplasmic and nuclear connexin expression. The levels of expression were correlated with the overall survival time (OS). Cx43 was overexpressed in tumour cells compared to epithelia in dysplasia-free mucosa. High membrane expression of Cx43 on tumour cells was the only statistically significant and independent prognostic factor of short OS (P=0.0088). Membrane expression of Cx43 in matching dysplasia-free mucosa acted similarly, but did not reach statistical significance (P=0.059). No correlation was found between the Cx26, Cx45 expression and OS. We conclude that Cx43 expression in dysplasia-free mucosa may indicate a very early stage of tumour promotion. Although overexpression of Cx43 is found in invasive tumours we only found membrane Cx43 expression to correlate with OS. This observation suggests that cytoplasmic Cx43 serves as storage and only membrane translocation may promote the formation of gap junctions and gap junctional intercellular communication (GJIC) with prognostic relevance.


miR-153 silencing induces apoptosis in the MDA-MB-231 breast cancer cell line.
MicroRNAs (miRNAs) are small, non-coding RNAs (18-25 nucleotides) that post-transcriptionally modulate gene expression by negatively regulating the stability or translational efficiency of their target mRNAs. In this context, the present study aimed to evaluate the in vitro effects of miR-153 inhibition in the breast carcinoma cell line MDA-MB-231. Forty-eight hours after MDA-MB-231 cells were transfected with the miR-153 inhibitor, an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was utilized to determine the effects of miR-153 on cell viability. Flow cytometry analysis and assessment of caspase 3/7 activity were adopted to determine whether miR-153 affects the proliferation rates and apoptosis levels of MDA-MB-231 cells. Our results showed that silencing of miR-153 significantly inhibited growth when compared to controls at 48 hours, reducing proliferation by 37.6%, and inducing apoptosis. Further studies are necessary to corroborate our findings and examine the potential use of this microRNA in future diagnostic and therapeutic interventions.


Tissue distribution, cellular source, and structural analysis of rat immunoreactive uroguanylin.
Uroguanylin, a member of the guanylin peptide family, acts on guanylyl cyclase C (GC-C) to regulate intestinal and renal fluid and electrolyte transport through the second messenger, cGMP. Using an antiserum raised against synthetic rat uroguanylin, we established an RIA and identified three endogenous molecular forms in the intestine and kidney: a 15-amino acid uroguanylin, an 18-amino acid uroguanylin that is a monobasic processing product, and a 9.4-kDa prouroguanylin. Prouroguanylin is the major molecular form in these two tissues, whereas only 15-amino-acid uroguanylin is present in the urine. Rat uroguanylin is most abundant in the proximal small intestine, its content decreasing toward the colon. Uroguanylin is present immunohistochemically in the endocrine cells in the intestine and stomach, B cells in the pancreatic islets, and tubular epithelial cells in the kidney. Uroguanylin has a widespread tissue distribution and is located in cells that function in an endocrine, paracrine, and/or luminocrine (luminal secretion) fashion. Uroguanylin may have physiological functions other than the regulation of fluid and electrolyte transport in the intestine and kidney.


Mechanism and Effect of Polar Styrenes on Scandium-Catalyzed Copolymerization with Ethylene.
Copolymerization of ethylene (E) and polar vinyl monomers remains a problem because E propagation is hindered. Herein, for the first time, we report the copolymerization of E and polar styrenes (SR ) by using an oxophilic scandium catalyst that exhibits higher turnover frequencies than both E and SR homopolymerizations when R is an electron-withdrawing group. This positive comonomer effect was elucidated through computing reaction profiles of E/SF copolymerization at the DFT (B3PW91) level of theory. It reveals that the secondary interaction between Sc3+ and phenyl of the last and penultimate inserted SF units leads to a decrease of the E insertion barrier, because the electron-withdrawing substituent enhances the electrophilicity of Sc3+ by an inductive effect mediated by the secondary interaction. After three consecutive insertions of the E units, the secondary interaction is lost and the SF insertion is kinetically preferred over the E insertion. This process is in line with the NMR spectrum analyses which show that the resultant copolymers mainly contain SR (E)x SR sequences where x≤3.


Differences in predominant enhancement mechanisms of superparamagnetic iron oxide and ultrasmall superparamagnetic iron oxide for contrast-enhanced portal magnetic resonance angiography. Preliminary results of an animal study original investigation.
To determine the effect of particle size of superparamagnetic iron oxide (SPIO) contrast agents on magnetic resonance angiography of the portal venous system. We studied eight beagle dogs by a T1-weighted 3D turbo-gradient echo magnetic resonance (MR) angiography sequence (TE 4 milliseconds, TR 11 milliseconds, flip angle 25 degrees, coronal imaging plane) before and after administration of either Resovist (SHU555A), a superparamagnetic iron oxide contrast agent with a mean particle size of 60 nm and a relaxivity ratio R2/R1 of approximately 7, or a new ultrasmall superparamagnetic iron oxide (USPIO) contrast agent with a mean particle size of approximately 20 nm and a R2/R1 ratio of approximately 2. Images were acquired on a 1.5-T MR body scanner. Both agents were injected as a peripheral bolus of 40 mumol Fe/kg body weight. Repeated scans were acquired before, immediately after, and 10, 20, 30, and 40 minutes after administration of the agent. After administration of Resovist, portal venous signal increased to 237% of control immediately after injection, while hepatic parenchymal signal intensity decreased to 86% of control. The maximal CNR increase to 177% was achieved immediately after injection of the agent. After USPIO, portal venous signal increased to 401% of the precontrast value immediately after injection, while hepatic parenchymal signal intensity also increased to 131% of control at this time. Hepatic signal then decreased progressively to 49% of control after 40 minutes. The maximal CNR increase to 326% was achieved 10 minutes after injection of the agent. It is concluded that superparamagnetic iron oxide particles of different sizes have different R2/R1 ratios and, consequently, different mechanisms of contrast improvement in T1-weighted portal MR angiograms.


The involvement of P2Y12 receptors, NADPH oxidase, and lipid rafts in the action of extracellular ATP on synaptic transmission at the frog neuromuscular junction.
Adenosine 5'-triphosphate (ATP) is the main co-transmitter accompanying the release of acetylcholine from motor nerve terminals. Previously, we revealed the direct inhibitory action of extracellular ATP on transmitter release via redox-dependent mechanism. However, the receptor mechanism of ATP action and ATP-induced sources of reactive oxygen sources (ROS) remained not fully understood. In the current study, using microelectrode recordings of synaptic currents from the frog neuromuscular junction, we analyzed the receptor subtype involved in synaptic action of ATP, receptor coupling to NADPH oxidase and potential location of ATP receptors within the lipid rafts. Using subtype-specific antagonists, we found that the P2Y13 blocker 2-[(2-chloro-5-nitrophenyl)azo]-5-hydroxy-6-methyl-3-[(phosphonooxy)methyl]-4-pyridinecarboxaldehyde did not prevent the depressant action of ATP. In contrast, the P2Y12 antagonist 2-methylthioadenosine 5'-monophosphate abolished the inhibitory action of ATP, suggesting the key role of P2Y12 receptors in ATP action. As the action of ATP is redox-dependent, we also tested potential involvement of the NADPH oxidase, known as a common inducer of ROS. The depressant action of extracellular ATP was significantly reduced by diphenyleneiodonium chloride and 4-(2-aminoethyl)-benzenesulfonyl fluoride hydrochloride, two structurally different inhibitors of NADPH oxidase, indicating that this enzyme indeed mediates the action of ATP. Since the location and activity of various receptors are often associated with lipid rafts, we next tested whether ATP-driven inhibition depends on lipid rafts. We found that the disruption of lipid rafts with methyl-beta-cyclodextrin reduced and largely delayed the action of ATP. Taken together, these data revealed key steps in the purinergic control of synaptic transmission via P2Y12 receptors associated with lipid rafts, and identified NADPH oxidase as the main source of ATP-induced inhibitory ROS at the neuromuscular junction. Our data suggest that the location of P2Y receptors in lipid rafts speeds up the modulatory effect of ATP. Uncovered mechanisms may contribute to motor dysfunctions and neuromuscular diseases associated with oxidative stress.


Effect of practice on visual backward masking.
Five experiments studied practice effects for 4, 7, 11 subjects on visual backward masking using a signal-detection procedure under various conditions. Exp. I determined the minimum perceptible critical stimulus duration (CSD) for criterion identification of a target stimulus, the letter T or A. In Exp. II, the stimulus was presented at the critical stimulus duration (CSD) followed by a pattern mask at intervals of 20 to 120 msec. for 15 separate sessions. In Exp. III (N = 4) the mask followed the CSD in intervals of 2-msec. increments until subjects reached criterion accuracy. Exps. IV and V (Ns = 4, 7) provided partial replications of Exps. II and III. Naive subjects were used, and the stimulus duration was constant for all subjects. When masking functions were obtained at a threshold, considerable variability was found and subjects improve slowly or not at all over sessions. With a fixed supra-threshold stimulus, all subjects improve with practice. The inportance of these findings is discussed as they relate to common (and largely untested) assumptions made in the backward masking and perception literature.


Dynamic increase of a 45,X cell line in a patient with multicentric ring Y chromosomes.
Because ring Y chromosomes are unstable during cell division most reported patients are mosaics, usually including a 45,X cell line. The phenotype varies from normal males or females with streak gonads to sexual ambiguities. We present here the case of a 23-year-old man who was referred at 11 years for growth delay. The GTG-banded karyotypes of lymphocytes revealed two cell lines: 46,X,dic r(Y) seen in 76% of the metaphases analyzed and 45,X (24%). Karyotypes and FISH were performed eight years later with the following probes: DYZ3 (Y centromere), SRY (sex-region of the Y), DYZ1 (Yq heterochromatin), CEPX/Y (X centromere and Yq heterochromatin), TelVysion Xp/Yp, Xq/Yq (X and Y subtelomeres), pan-telomeric, cosmid clones LLycos130G04 and LLycos37C09 (PARII), and BAC clone RP11-5C5 (Yq11.223). The results showed an increase in the 45,X cell line (60%) and a reduction in the 46,X,dic r(Y) cell line (36.4%). The use of Yq probes showed that the ring Y chromosome was dicentric. In addition, other ring Y structures were observed. The breakpoints occurred in proximal Yp11.32 or in Yp11.31 distal to SRY and in Yq12 distal to the PARII region. Therefore, most of the Y remained intact and all genes, with the exception of those in PARI, are present in double dosage in the dic r(Y). The level of mosaicism was important in defining the phenotype.


Primitive neuroectodermal tumor after radiation therapy for craniopharyngioma.
The authors report a case of primitive neuroectodermal tumor induced by radiation therapy of craniopharyngioma. This African-American male patient originally presented with craniopharyngioma, for which he underwent resection and whole-brain radiation therapy. Eight years later, at the age of 20 years, he returned with a left facial droop and left hemiparesis. A right basal ganglia mass was identified and resected. Histopathological examination identified the lesion as primitive neuroectodermal tumor. Although radiation therapy has shown to be beneficial in decreasing the recurrence rate in subtotally resected craniopharyngioma, the risks of radiation treatment should be clearly communicated to the patients, their families, and neurosurgeons before starting such treatment. This report expands the spectrum of reported radiation-induced neoplasms in the CNS.


Predictive value of non-invasive parameters in patients with left ventricular hypertrophy during a five-year follow-up period.
Regardless of other known factors, left ventricular hypertrophy is considered to be a significant factor which correlates with the risk of cardiovascular complications. In practice, it is very important to predict the outcome for every patient at the beginning of the treatment. The aim of the study was to follow the predictive value of non-invasive parameters obtained at the beginning of the study in patients with essential arterial hypertension and left ventricular hypertrophy who were treated by regular therapy through a five year follow-up period. Ninety patients (average age 55) with essential hypertension and left ventricular hypertrophy were examined. All patients were studied at baseline after temporary discontinuation of previous antihypertensive therapy. The follow-up period started at the baseline examination and lasted for five years. Adverse cardiovascular events occurred in 15 (16.7%) patients. Non-invasive parameters were tested by stepwise multiple regression analysis. Three examined parameters had predictive value: QTc interval dispersion (beta = 0.325, p = 0.001), septal wall thickness (beta = 0.294, p = 0.003) and low increase of the heart rate during exercise testing (beta = -0.202, p < 0.04). For this model, adjusted R square = 0.203; F3,84 = 8.406, p < 0.0001. In spite of regular medical treatment, patients with larger QTc dispersion, greater septum thickness and lower increase of heart rate during exercise testing showed worse outcome through the follow-up period. These patients should be recognized as early as possible and treated more aggressively.


Diagnostic transcranial magnetic stimulation as a method of objective evaluation of motor pathways in patients with neoplastic and infectious brain damage.
The aim of our study was to evaluate validity of transcranial magnetic stimulation as evaluation tool of motor pathways condition dynamics in patients with gliomas and meningitis. There were included 91 patients: 40 children with aseptic meningitis, 26 matching age controls, 10 adults with gliomas and 16 matching controls. All patients underwent transcranial magnetic stimulation (TMS) before and after the treatment. TMS showed good tolerability in all groups. Significant improvement of central motor pathways conductivity (MEPs amplitudes) was seen in both groups. In meningitis group significant rising of functional state of motoneurons was seen as well. We propose that TMS proved to be effective evaluation tool of motor pathways condition dynamic in patients with gliomas and meningitis.


Randomised double-masked placebo-controlled trial of a treatment for congenital nystagmus.
Several therapies have been developed for congenital nystagmus (CN) but without placebo-controlled trials. We investigated a treatment which combined two therapies that had been advocated by several authors and were reported to improve visual acuity (VA). A placebo treatment was designed to mimic the time, attention, 'high tech' apparatus, and the explanation used in the experimental treatment. To each group, 38 subjects with CN were randomly allocated. Their VA and contrast sensitivity (CS) were assessed three times before undergoing treatment for 6 weeks and then once more. An improvement in VA occurred, however, this was not significantly different in the two groups. The improvement in CS was greater in the experimental than in the control group, but the difference failed to reach significance in most statistical tests. We conclude that putative therapies for CN should be assumed to be placebos until proven otherwise with randomized controlled trials.


Characterization of alpha1-adrenoceptor subtypes mediating noradrenaline-induced contraction of rat epididymal vas deferens in calcium-free medium.
The alpha1-adrenoceptor subtype mediating noradrenaline (NA)-induced contractions of rat epididymal vas deferens in Ca2+-free/EGTA (1 mM) medium was studied using competitive antagonists. The effects of chloroethylclonidine (CEC) was investigated in Ca2+-free and normal Krebs' medium and RT-PCR was used to identify alpha1-adrenoceptor specific mRNA in epididymal vas deferens. In Ca2+-free medium, NA evoked sustained contractions but was less potent (pD2, 5.9) than in normal Krebs' medium (pD2, 7.3). The contractions in Ca2+-free medium were inhibited by prazosin (pA2, 9.3), 5-methylurapidil (pA2, 8.4), spiperone (pA2, 7.6) and BMY 7378 (pK(B), 6.8) consistent with activation of alpha1A-subtype. Repeated pretreatment with CEC (100 microM) reduced the potency of NA and maximum contractions in normal and Ca2+-free media. CEC-sensitivity in normal Krebs' medium was enhanced by prior treatment with phenoxybenzamine. mRNA for alpha1a- and alpha1d- but not alpha1b-adrenoceptors were detected in epididymal vas deferens. These results suggest that NA contracts the tissue in Ca2+-free medium by the stimulation of alpha1A-adrenoceptors. Two factors affecting CEC-sensitivity of NA-induced contractions in this tissue are discussed.


Factors impeding dispatcher-assisted telephone cardiopulmonary resuscitation.
Dispatcher-assisted telephone cardiopulmonary resuscitation (CPR) instruction can increase the proportion of sudden cardiac arrest victims who receive bystander CPR and has been associated with improved survival. Most sudden cardiac arrest victims, however, do not receive bystander CPR. The study objective was to examine factors that may impede implementation of telephone CPR. We reviewed dispatcher audio recordings and emergency medical services reports for 404 cases of sudden cardiac arrest that occurred from July 1, 2000, to June 30, 2002, in the study county to assess the phase (1, instructions not offered; 2, instructions offered but declined; or 3, instructions offered and accepted but CPR not implemented) and specific factors within each phase that potentially impede telephone CPR. Twenty-five percent (99/404) of victims received bystander CPR without dispatch assistance, 34% (139/404) received telephone CPR, and 41% (166/404) did not receive bystander CPR. Each phase of telephone CPR process impeded the implementation of CPR: (1) instructions not offered in 48% (80/166); (2) instructions offered but declined in 31% (52/166); and (3) instructions offered and accepted but CPR not implemented in 21% (34/166). During the first phase, telephone CPR was potentially impeded most frequently because the victim was reported to have signs of life (51/80, 64%); during the second and third phases, telephone CPR was most often impeded because of bystander physical limitation (32/86, 37%). Emotional distress, disease transmission, disagreeable victim characteristics, or medicolegal concerns uncommonly impeded telephone CPR (10/86, 12%). Factors potentially impeding telephone CPR can be identified. Although many are logistically challenging, some may be addressable and hence provide opportunities to strengthen the chain of survival.


Identification, localization and expression of LPXRFamide peptides, and melatonin-dependent induction of their precursor mRNA in the newt brain.
The existence of RFamide peptides with a C-terminal LPXRFamide (X=L or Q) motif has been identified in the brain of various vertebrate species. However, the presence of LPXRFamide peptides in the urodele brain is not yet known. In this study, we cloned a cDNA encoding the precursor of LPXRFamide peptides from the newt brain by a combination of 3' and 5' rapid amplification of cDNA ends. The deduced LPXRFamide peptide precursor consisted of 233 amino acid residues, encoding four putative LPXRFamide peptides. All the peptide sequences were flanked by a glycine C-terminal amidation signal and basic amino acid on each end as an endoproteolytic site. Mass spectrometric analyses detected a nonapeptide, two decapeptides and an octapeptide produced from the precursor polypeptide in the brain as endogenous ligands. In situ hybridization further revealed the cellular localization of newt LPXRFamide (nLPXRFa) precursor mRNA in the suprachiasmatic nucleus (SCN) in the newt hypothalamus. Immunocytochemistry showed a cluster of cell bodies restricted to the SCN and their terminals in the median eminence. To understand the regulatory mechanism of nLPXRFa peptide expression, we further analyzed the effect of melatonin on the expression of nLPXRFa precursor mRNA. Melatonin administration to newts increased the expression of nLPXRFa precursor mRNA in the diencephalon. These results indicate that the urodele hypothalamus possesses LPXRFamide peptides and the expression of LPXRFamide peptides is regulated by melatonin. The localization of nLPXRFa peptides further suggests that these peptides may be involved in the regulation of pituitary hormone release in newts.


Template matching based object recognition with unknown geometric parameters.
In this paper, we examine the problem of locating an object in an image when size and rotation are unknown. Previous work has shown that with known geometric parameters, an image restoration method can be useful by estimating a delta function at the object location. When the geometric parameters are unknown, this method becomes impractical because the likelihood surface to be minimized across size and rotation has numerous local minima and areas of zero gradient. We propose a new approach where a smooth approximation of the template is used to minimize a well-behaved likelihood surface. A coarse-to-fine approximation of the original template using a diffusion-like equation is used to create a library of templates. Using this library, we can successively perform minimizations which are locally well-behaved. As detail is added to the template, the likelihood surface gains local minima, but previous estimates place us within a well-behaved "bowl" around the global minimum, leading to an accurate estimate. Numerical experiments are shown which verify the value of this approach for a wide range of values of the geometric parameters.


Importance, localization and functional properties of the cell-associated form of plasminogen activator in mouse peritoneal macrophages.
In inflammatory macrophages, plasminogen activator exists in two active forms, a soluble form released into the extracellular medium and a cell-associated form. This communication describes some properties of the cellular form of plasminogen activator, in intact macrophages and in cell lysates. Cellular plasminogen activator is a membrane protein, associated with the outer face of the plasma membrane; in intact macrophages, it participates in the activation of exogenous plasminogen and, thus, has to be considered as an ectoenzyme. A plasminogen activator activity can be detected in cell lysates (macrophage monolayers lysed in 0.1% Triton X-100) only when plasmin production is followed by the use of small synthetic substrates because a soluble inhibitor, released during extraction, blocks plasmin fibrinolytic activity. In these lysates, plasminogen activator molecules exist as high molecular weight unstable complexes exhibiting a high affinity for plasminogen.


A combined supplementation of vitamin B12 and n-3 polyunsaturated fatty acids across two generations improves nerve growth factor and vascular endothelial growth factor levels in the rat hippocampus.
Vitamin B12 and n-3 polyunsaturated fatty acid (n-3 PUFA) are known to influence cognition. This study aims to examine if these nutrients affect the protein levels and gene expression of nerve growth factor (NGF) and vascular endothelial growth factor (VEGF) in the cortex and hippocampus in the second-generation offspring at 3 mo of age. Wistar rats were fed the following diets for two generations: Control (CON), vitamin B12 deficient (VBD), vitamin B12 deficient supplemented with n-3 PUFA (VBDO), vitamin B12 supplemented (VBS), vitamin B12 supplemented with n-3 PUFA (VBSO). The VEGF and NGF gene expression and protein levels in the hippocampus were lower (P⩽0.01) in the VBD group as compared to the CON group while the VBDO group restored the VEGF and NGF gene expression (P⩽0.01). The VBS group showed similar levels of NGF and VEGF to that of the CON group. However, the VBSO group demonstrated higher (P⩽0.05) NGF gene expression and protein levels in the hippocampus and higher cortex NGF protein levels as compared to the CON group. In addition, VEGF (in hippocampus) and NGF (in cortex and hippocampus) protein levels were also higher (P⩽0.05) in the VBSO group as compared to the VBS group. Our results indicate that the combined supplementation of vitamin B12 and n-3 PUFA improves NGF and maintains VEGF levels in the brain which may improve neurovascular function.


Prevalence of BRCA1/2 large genomic rearrangements in Chinese women with sporadic triple-negative or familial breast cancer.
The prevalence of BRCA1/2 large genomic rearrangements (LGRs) and their underlying mechanisms have not been fully evaluated in Chinese women with breast cancer. In this study, we determined the prevalence of BRCA1/2 LGRs in 834 patients with familial breast cancer (FBC) and 660 patients with sporadic triple-negative breast cancer (TNBC) who were negative for BRCA1/2 small-range mutations using the multiplex ligation-dependent probe amplification method. We found that 20 index patients (2.4%) in the FBC group carried a BRCA1 or BRCA2 LGR, and the frequencies of BRCA1 and BRCA2 LGRs were 1.6% and 0.8%, respectively. Seven index patients (1.1%) carried a BRCA1 LGR in 660 sporadic TNBC patients, whereas no BRCA2 LGRs were found in these patients. Among the BRCA1/2 LGRs, 48.1% (13/27) were novel, and the breakpoints of the majority of the LGRs were identified. ΨBRCA1-mediated homologous recombination (HR) and Alu-mediated HR/non-homologous end-joining (NHEJ) accounted for 40% and 30% of the BRCA1 LGRs, respectively. Alu-mediated HR accounted for 71.4% of the BRCA2 LGRs, and the remaining one-third was generated through Long interspersed nuclear elements (LINE)-mediated NHEJ. Our findings suggest that both FBC patients and sporadic TNBC patients should be tested for BRCA1/2 LGRs.


Predictive factors of liver injury in blunt multiple trauma.
This study was conducted to clarify whether injuries that are likely to be revealed by initial clinical and conventional radiological examination at the trauma bay (e.g., right-side rib fractures) meaningfully contribute to the prior probability of accompanying hepatic lesions in multiple injured patients. Fifty-five subjects (sampled from a cohort of 218 patients) with liver injury fulfilling the definition of polytrauma were compared with 55 polytrauma patients without liver injury. Controls were individually matched for age, gender, and Injury Severity Scores. Whole-body, helical, contrast-enhanced computed tomography was applied to all participants. We modeled independent predictors of liver involvement by conditional logistic and random-effects regression analysis. In the present sample, the prevalence of hepatic injury was 25.2%. Neither the injury mechanism (car crash, pedestrian accident, fall from height) nor certain accompanying injuries (right-side serial rib fractures, lumbar spine fractures) predicted the presence of hepatic injury. Liver injury was particularly unlikely in bikers [odds ratio (OR) 0.78, 95% confidence interval (CI) 0.59-1.03] and patients with left-side rib fractures (OR 0.80, 95% CI 0.66-0.98). There are no index injuries that will reliably indicate the presence of liver involvement in multiple trauma cases. Also, the absence of these injuries cannot rule out liver damage.


Experimental study on the effects of +Gz. Acceleration under gestational conditions. I. Ultrastructural myocardial lesions.
In the course of a complex experimental study concerning the effects of highly positive acceleration on gestation and development of the neonate, investigations were carried out of ultrastuctural myocardial lesions in the pregnant rat exposed to prolonged gravitational stress (+ 2G). The experimental animals presented various disseminated and partly irreversible myocardial lesions whose pathogeny is discussed.


The importance of social comparisons for high levels of subjective quality of life in chronic schizophrenic patients.
In schizophrenic patients, quality of life (QoL) studies often find high levels of general life satisfaction and satisfaction in various life domains despite deprived living conditions. Therefore, the usefulness of QoL as an outcome indicator has been questioned. Since social comparison processes have been postulated to be related to the level of satisfaction, this hypothesis was analysed empirically by the present study in schizophrenic patients. Satisfaction and social comparisons of 148 schizophrenic inpatients and 66 mentally healthy controls were examined with regard to the domains 'health' and 'family' by means of a standardised interview. The schizophrenic patients had a history of either long-term (n = 75) or short-term (n = 73) restricted and deprived living conditions. Long-term patients showed significantly higher satisfaction levels than short-term patients. They compared themselves predominantly laterally or downwards with fellow inpatients. Significant relationships between the direction of social comparisons and satisfaction ratings were found in all three samples. Social comparisons proved to be important for the level of satisfaction in schizophrenic patients. Results indicate that experiences of restricted and deprived living conditions induce accommodation processes and response-shifts that should be taken into account in the interpretation of quality-of-life data.