Platelet-derived growth factor receptor kinase inhibitor AG1295 and inhibition of experimental proliferative vitreoretinopathy.
Receptor tyrosine kinase (RTK) activation is critical for growth factor-mediated cell proliferation. The present study was designed to determine the effect of tyrphostin AG1295, a selective blocker of platelet-derived growth factor (PDGF) RTK, on proliferative vitreoretinopathy (PVR) development. Rabbit conjunctival fibroblasts cells (1 x 10(4)) were seeded into 96-well plates and maintained in Dulbecco's modified essentialmedium (DMEM) with 0.5% fetal bovine serum. The cells were exposed to 50 ng/mL PDGF-AAor PDGF-BBor phosphate-buffered saline with or without AG1295 (1 microM, 10 microM, and 100 microM). After 3 days, the viable cells in each well were measured by 3,(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Homologous rabbit conjunctival fibroblasts were injected intravitreally, followed by injection of 100 microM of AG1295. The development of tractional retinal detachment (TRD) was assessed to evaluate the effect of AG1295 in vivo. Electroretinography and histologic studies were performed after intravitreal injection of AG1295 into untreated eyes to evaluate toxicity. Two concentrations of AG1295 (10 and 100 microM) significantly inhibited rabbit conjunctival fibroblast cell growth stimulated by PDGF-AA or PDGF-BB in vitro. Development of TRD was significantly attenuated (P <.01) with 100 microM of AG1295 until day 21. No significant histologic or retinal functional damage was found in the AG1295-treated group. PDGF receptor specific inhibitor AG1295 attenuated PVR without significant side effects in rabbits. This reagent could be a useful treatment to prevent PVR.


The chromatic parameters of isoluminant chromatic motion examined with dissimilarity judgements.
A moving edge or contrast between equiluminant colours produces a weaker motion percept than that defined by luminance contrast. However, the specific contrasts that determine chromatic motion have not been explored systematically. Here, rivalrous chromatic motion displays were produced by superimposing two gratings, one drifting from left to right and the other in the opposite direction. Each grating oscillated between equiluminant endpoints chosen from a pool of 16 colours. The rivalrous ambiguity resolved spontaneously for each display as the more-dissimilar colour pair dominated the less-dissimilar pair, and produced a percept of motion in the corresponding direction. These dissimilarity judgements were analysed with multidimensional scaling to represent 'motion salience' as distances in a colour map, to gauge whether chromatic motion is enhanced or weakened if the oscillation aligns with particular directions in the colour plane. Judgements were compared with other control judgements involving standard subjective dissimilarities between the same stimuli. Notably, chromatic motion was strongest when grating endpoints were separated along an orange-blue direction. This does not coincide with either cardinal axis of cone space, (L-M) or S(0) , but rather is a direction that would arise if motion is computed from a combination of the (L-M) and S(0) signals.


Gangliosides modulate proliferation, migration, and invasiveness of human brain tumor cells in vitro.
Gliomas, the most common form of intrinsic brain tumor, are characterized by diffuse local invasion of the normal brain structures, irrespective of their histological grade of malignancy; a feature that is a major obstacle to successful therapy. They generally infiltrate the central nervous system (CNS) as individual tumor cells several centimeters beyond the macroscopic tumor margin and consequently often recur, after subtotal surgical resection. Factors involved in the control of both their proliferation and invasiveness are poorly documented. In this work, the role of gangliosides on proliferation of both human fetal human brain cells and five cell lines derived from human gliomas with different grades of malignancy was investigated. In addition, 8 microns-porosity polycarbonate filters were used to study cell motility. In addition, these filters were coated with the reconstituted extracellular matrix (ECM) composite, Matrigel, to assess invasiveness. The results presented show that gangliosides generally exert a proliferation inhibitory effect on fetal brain cells and glioma cell lines in vitro and play an important role in promoting glioma cell motility and invasiveness. The molecular mechanisms involved in the action of gangliosides may prove useful in identifying new targets for an anti-invasion therapy.


Calretinin expression in specific neuronal systems in the brain of an advanced teleost, the grey mullet (Chelon labrosus).
The distribution of calretinin (CR) in the brain of an "advanced" teleost, the grey mullet, was studied by using immunoblotting and immunocytochemical techniques. In immunoblots of protein extracts of rat and mullet brains, the CR antibody stained a single band of about 29 kDa. CR immunoreactivity was observed in specific neuronal populations of all brain regions. The primary olfactory system, the optic nerve fibers, and some sensory fibers of other cranial nerves exhibited strong CR immunoreactivity. In the forebrain, the CR-immunoreactive (CR-ir) populations were scarce in the telencephalon and hypophysiotrofic hypothalamus, but numerous in many specialized nuclei of the diencephalon (preglomerulosus complex, nucleus glomerulosus, anterior glomerular nucleus, nucleus diffusus) and pretectum (parvocellular and magnocellular superficial pretectal nuclei, central pretectal nucleus), which are related to sensory systems. The two main forebrain bundles, medial and lateral, contained numerous CR-ir fibers. The midbrain sensory centers (optic tectum and torus semicircularis) exhibited numerous CR-ir cells and fibers. Likewise, the secondary gustatory nucleus of the isthmus is one of the nuclei exhibiting more intense CR immunoreactivity. Characteristically, the efferent cerebellar system (eurydendroid cells and brachium conjunctivum) and some afferent cerebellar fibers were CR-ir. In the medulla oblongata, a number of reticular cells, the inferior olive, and the magnocellular octaval nucleus exhibited CR immunoreactivity. CR-ir motoneurons were also observed in the spinal cord and in the oculomotor nucleus. Together with results obtained in other vertebrates, present results suggest that neural systems using calretinin to maintain intracellular calcium concentration have been rather well conserved during vertebrate evolution.


Effects of mixture ratio and hydraulic retention time on single-stage anaerobic co-digestion of food waste and waste activated sludge.
The biochemical methane potential (BMP) test was used to evaluate the anaerobic biodegradabilities of food waste (FW), waste activated sludge (WAS), and the mixtures having the ratios of 10:90, 30:70, 50:50, 70:30, and 90:10 (FW:WAS) on a volatile solid (VS) basis. The carbon/nitrogen (C/N) ratio and the biodegradability of the mixtures improved from 6.16 to 14.14 and increased from 36.6 to 82.6% as the FW proportion of the mixture increased from 10 to 90%, respectively. The stability and performance of the single-stage anaerobic digester (SSAD) for the co-digestion of FW and WAS were investigated, operated at the hydraulic retention times (HRTs) of 10, 13, 16, and 20 days with five mixtures at 35 degrees C, respectively. During all the experiments, there were no indication of failure such as low pH, insufficient alkalinity, ammonia inhibition, and the accumulation of volatile fatty acids (VFAs) in any of the digesters, and the buffer capacity was the highest in the digester fed with a feed mixture of 50:50. The optimum operating conditions of the SSAD were found to be an HRT of 13 days and a mixture of 50:50 in terms of the buffer capacity of the digester and the effluent VS concentration, the methane content of the biogas produced and the specific methane production (SMP). The VS removal efficiency, biogas production rate (GPR), and SMP in this condition achieved 56.8%, 1.24 m3 m(-3) d(-1) and 0.321 m3 CH4 kg(-1) VS(fed)(-1) with an organic loading rate (OLR) of 2.43 kg VS m(-3) d(-1).


Extrarenal nephroblastomas.
The cases of extrarenal nephroblastoma published in the world literature have been tabulated and reviewed, and are discussed from a historical point of view.


Fluid skills: drinking games and alcohol consumption among Australian university students.
The objective of this study was to assess participation in drinking games among Australian university students; to determine the range of games played, their context and participant motivations; and to analyse the impact of games on alcohol consumption and its adverse consequences. We used a cross-sectional survey incorporating structured interviews and a self-administered questionnaire with students between 18 and 25 years of age at the University of Western Australia. This was a qualitative assessment of drinking game typology and contexts and participant motivation. Quantitative outcomes were rate and frequency of participation in drinking games; amount and rate of alcohol consumption during games; incidence of adverse outcomes following participation. Twenty-seven interview responses and 256 questionnaire responses were analysed for qualitative and quantitative outcomes, respectively. The qualitative analysis enabled categorisation of drinking games by skill and competitive nature, with varying influence on hazardous drinking. Common reported motivations for play included boredom, social pressure and social unease. The associated heavy drinking and possible hazards were well recognised but did not affect the decision to play. In the quantitative arm, most drinkers (74%) reported having participated in a drinking game. Game players reported playing an average of four drinking games in the previous 6 months. An average of six standard drinks was consumed during the most recent game. Pressure to participate from others was reported by 60% of game participants, while 50% reported that they had placed pressure on others to participate. Half (51%) reported an adverse outcome following participation. Loss of consciousness due to drinking was experienced or witnessed by 89% of game players, of whom 63% reported that the person was put to bed, while 54% reported that the person was watched. Participation in drinking games was common, and plays an important social role in this group. Drinking games were associated commonly with binge drinking and adverse outcomes. Future harm minimisation strategies targeting this group should address the particular risks of these games.


Hallervorden-Spatz disease.
In a 22 year old man with dominant extrapyramidal signs, dystonia and mental deterioration, magnetic resonance imaging revealed marked overall low signal from the globus pallidus on each side, with central zones of high signal on T2-weighted spin echo sequences. There was also a strikingly low signal in the zona reticularis of the substantia nigra, consistent with Hallervorden-Spatz disease.


Review of attrition and adherence in exercise studies following hematopoietic stem cell transplantation.
Implementing exercise programs in people receiving high-dose chemotherapy followed by bone marrow (BMT) or hematopoietic stem cell transplantation (SCT) presents unique challenges. This review examines subject attrition rates and reasons for attrition as well as adherence to exercise interventions following BMT/SCT. Studies published between January 1985 and December 2012 that prospectively tested an exercise intervention following BMT or SCT were included in the review. Evaluation criteria included: (1) exercise modality; (2) the amount of supervision required to implement the intervention; (3) timing of the intervention; (4) subject attrition rates and reasons for attrition; and (5) exercise adherence rates. Of the 20 studies reviewed, most tested an aerobic exercise intervention or a combination of aerobic and strength training. Supervised exercise sessions were more commonly used than unsupervised sessions. The overall attrition rate was 18% for the 998 subjects enrolled in the studies. Major reasons for attrition included death, change in health status, protocol issues, personal issues with subjects, and lost to follow-up/no reason provided. Authors of supervised exercise programs rarely published exercise adherence information. Unsupervised exercise programs relied mainly on self-report to document adherence. Exercise research following BMT/SCT is becoming more sophisticated as researchers build upon the expanding literature base. Questions regarding subject attrition and adherence to exercise interventions must be addressed to identify interventions that are likely to be successful when translated into clinical practice. Subject attrition from exercise studies following BMT/SCT is relatively low. Adherence information for exercise interventions needs to be regularly addressed.


[Removal of bamboo fragments transorbitally penetrated into the cerebellum and temporal lobe 30 years after the injury].
A 37-year-old male presented with transorbitally penetrating bamboo fragments, which resulted in multiple brain abscesses during 30 years. Neurological examination revealed left blindness, oculomotor palsy, trigeminal nerve (V1) anesthesia, and cerebellar ataxia. Computed tomography demonstrated foreign bodies and two ring enhanced lesions in the cerebellum. Magnetic resonance imaging demonstrated a hypointense mass penetrating through the cavernous sinus into the posterior fossa, and another mass into the temporal lobe. Cerebral angiography showed that the sylvian vein drained to the pterygoid plexus. Two weeks after the drainage of two cerebellar abscesses using an endoscope, bamboo fragments were removed using a zygomatic anterior petrosal approach. Occlusion of the draining vein to the pterygoid plexus might cause temporal venous infarction. Using indocyanine green intraoperative angiography, we confirmed the collateral venous flow of the sylvian vein after temporary occlusion of the draining vein to the pterygoid plexus. Postoperative course was uneventful. Foreign bodies must be removed even after 30 years to prevent repetitive brain abscesses.


Bradykinin produces pulmonary vasodilation in fetal lambs: role of prostaglandin production.
Bradykinin produces pulmonary vasodilation and also stimulates production of other pulmonary vasodilators, including prostaglandin I2 (PGI2) and endothelial-derived relaxing factor. In 12 chronically instrumented fetal lambs, we therefore investigated potential mediation of the bradykinin response by PGI2 or other cyclooxygenase products. A 15-min infusion of bradykinin (approximately 1 microgram/kg estimated fetal wt/min) increased fetal pulmonary blood flow by 522% (P less than 0.05) and decreased pulmonary vascular resistance by 86% (P less than 0.05); plasma 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) concentration also increased (P less than 0.05). After cyclooxygenase inhibition by indomethacin (3 mg), bradykinin increased pulmonary blood flow by only 350% (P less than 0.05) and decreased pulmonary vascular resistance by 83% (P less than 0.05); plasma 6-keto-PGF1 alpha concentrations did not increase. The increase in pulmonary blood flow produced by bradykinin was greater before administration of indomethacin than after (P less than 0.05). These studies demonstrate that bradykinin produces fetal pulmonary vasodilation by at least two mechanisms, one dependent on and the other independent of PGI2 production, the latter mechanism predominating.


Hensin, the polarity reversal protein, is encoded by DMBT1, a gene frequently deleted in malignant gliomas.
The band 3 anion exchanger is located in the apical membrane of a beta-intercalated clonal cell line, whereas the vacuolar H(+)-ATPase is present in the basolateral membrane. When these cells were seeded at confluent density, they converted to an alpha-phenotype, localizing each of these proteins to the opposite cell membrane domain. The reversal of polarity is induced by hensin, a 230-kDa extracellular matrix protein. Rabbit kidney hensin is a multidomain protein composed of eight SRCR ("scavenger receptor, cysteine rich"), two CUB ("C1r/C1s Uegf Bmp1"), and one ZP ("zona pellucida") domain. Other proteins known to have these domains include CRP-ductin, a cDNA expressed at high levels in mouse intestine (8 SRCR, 5 CUB, 1 ZP), ebnerin, a protein cloned from a rat taste bud library (4 SRCR, 3 CUB, 1 ZP), and DMBT1, a sequence in human chromosome 10q25-26 frequently deleted in malignant gliomas (9 SRCR, 2 CUB, 1 ZP). Rabbit and mouse hensin genomic clones contained a new SRCR that was not found in hensin cDNA but was homologous to the first SRCR domain in DMBT1. Furthermore, the 3'-untranslated regions and the signal peptide of hensin were homologous to those of DMBT1. Mouse genomic hensin was localized to chromosome 7 band F4, which is syntenic to human 10q25-26. These data suggest that hensin and DMBT1 are alternatively spliced forms of the same gene. The analysis of mouse hensin bacterial artificial chromosome (BAC) genomic clone by sequencing and Southern hybridization revealed that the gene also likely encodes CRP-ductin. A new antibody against the mouse SRCR1 domain recognized a protein in the mouse and rabbit brain but not in the immortalized cell line or kidney, whereas an antibody to SRCR6 and SRCR7 domains which are present in all the transcripts, recognized proteins in intestine, kidney, and brain from several species. The most likely interpretation of these data is that one gene produces at least three transcripts, namely, hensin, DMBT1, and CRP-ductin. Hensin may participate in determining the polarized phenotype of other epithelia and brain cells.


Diagnostic imaging of tarsal and metatarsal stress fractures. Part II.
As the preoccupation with physical fitness grows in this country, the problem of "stress fracture" has become more clinically significant. Reliable techniques for imaging the musculoskeletal system have also continued to grow, allowing the clinician to better diagnose and manage this condition. However, the radiographic findings of stress fracture are sometimes difficult to interpret. This review compares plain radiography, scintigraphy, CT, and MRI in the imaging of stress fractures.


Integration of Metabolomics and Transcriptomics To Reveal Metabolic Characteristics and Key Targets Associated with Cisplatin Resistance in Nonsmall Cell Lung Cancer.
Continuous exposure to cisplatin can induce drug resistance to limit efficacy; however, the underlying mechanisms correlated with cisplatin resistance are still unclear. Drug-sensitive A549 cells and cisplatin-resistant A549/DDP cells were used to explore the potential metabolic pathways and key targets associated with cisplatin resistance by integrating untargeted metabolomics with transcriptomics. Data are available via ProteomeXchange with identifier PXD013265. The results of comprehensive analyses showed that 19 metabolites were significantly changed in A549/DDP versus A549 cells, and some pathways had a close relationship with cisplatin resistance, such as the biosynthesis of aminoacyl-tRNA, glycerophospholipid metabolism, and glutathione metabolism. Moreover, transcriptomics analysis showed that the glutathione metabolism was also obviously affected in A549/DDP, which indicated that the glutathione metabolism played an important role in the process of drug resistance. Meanwhile, transcriptomics analysis suggested the four enzymes related to glutathione metabolism-CD13, GPX4, RRM2B, and OPLAH-as potential targets of cisplatin resistance in nonsmall cell lung cancer. Further studies identified the overexpression of these four enzymes in A549/DDP. The elucidation of mechanism and discovery of new potential targets may help us have a better understanding of cisplatin resistance.


Cell-mediated cytolysis of equine herpesvirus-infected cells by leukocytes from young vaccinated horses.
The objective of this study was to determine whether the administration of modified-live equine herpesvirus (EHV-1) to young horses with residual maternal antibodies stimulated EHV-specific cytolytic responses, and whether these responses were crossreactive between EHV-1 and EHV-4. Eighteen clinically normal Belgian cross-foals were used in the study and were commingled in two adjacent pens. Skin biopsies were harvested from 16 foals within 24 h of birth and fibroblast cultures were established, expanded and cryopreserved. Beginning at approximately 10 weeks of age, 10 randomly chosen foals were inoculated on days 0, 21, and 43 of the study with a vaccine containing modified-live EHV-1. Blood mononuclear leukocytes were obtained on days 0, 32, and 50 for the assessment of EHV-specific cytolytic activity using 5 h and 18 h chromium release assays. EHV-1-specific antibodies were assessed by enzyme-linked immunosorbent assay using serum collected on days -21, 0, 32, and 50 of the study. Lymphocyte blastogenic tests and bioassays for interferon activity were conducted on day 50. After two vaccinations, mononuclear leukocytes from seven of ten vaccinated foals had cytolytic activity against autologous EHV-1 cells and leukocytes from six of ten lysed EHV-4-infected cells when tested in an 18 h assay. This activity was enhanced by exogenous interleukin 2 and was markedly reduced using target cells from unrelated horses. Cytotoxicity was not detected in a 5 h assay following in vitro stimulation of leukocytes. After three vaccinations, blood leukocytes from 6/6 vaccinated foals and 0/6 unvaccinated foals had proliferative responses EHV-1. There were no significant differences in interferon production by leukocytes from these foals. Twelve foals tested had low concentrations of (maternal) EHV-1-specific antibody prior to vaccination. Five of eight foals tested had increases in EHV-specific antibodies, while 4/4 commingled unvaccinated foals had a decrease or no change in EHV-specific antibodies. These results demonstrate cytotoxic cellular immune responses can be induced in young horses with maternal antibodies following administration of modified-live vaccine.


Specific [3H]8-OH-DPAT binding in brain regions of rats genetically predisposed to various defense behavior strategies.
Distribution of 5-HT1A receptors was studied in rats genetically predisposed to two basic defense strategies--passive (freezing) or active (aggression) defensive behavior. Specific [3H]8-OH-DPAT binding was assayed in the brain structures of rat strains bred for 40 generations from Wistar stock for predisposition to freezing (catalepsy), and in wild rats bred for low and high aggression to humans. Considerable changes in [3H]8-OH-DPAT binding were found in the brain of rats with hereditary predisposition to catalepsy. A significant decrease in Bmax of specific receptor binding of [3H]8-OH-DPAT in the frontal cortex, and in the striatum as well as an increase in Kd in the hippocampus of cataleptic rats was shown. A clear-cut tendency to decrease of 5-HT1A receptor density was observed in the midbrain and hypothalamus of these rats. A comparison of wild Norway rats bred for aggressiveness against humans with those bred for the absence of affective aggressiveness showed a Bmax decrease without Kd change in the frontal cortex, hypothalamus, and amygdala of aggressive animals. It is hypothesized that 5-HT1A and probably 5-HT1A-like 5-HT7 serotonin receptors are involved in the mechanisms of both active and passive defense reactions, and the high expression of fear-induced defense is associated with their decrease in the frontal cortex. At the same time, the genetically determined preference for a certain defense behavior strategy depends either on the peculiarities of distribution of these receptor types in the brain regions or on some other types of serotonin receptors.


Postnatal development of evoked responses in the auditory cortex of the cat.
Postnatal development of the auditory evoked cortical response was investigated in the cat by laminar field potential analysis. Responses were induced by electrical stimulation of the cochlear nuclear complex and by sonic stimulation under sodium pentobarbital anesthesia. As is well known, the auditory evoked cortical response in adult cats is a diphasic positive-negative wave in the superficial cortical layers and a negative-positive wave in the deeper cortical layers. By contrast, the cortical response in neonatal kittens was a monophasic negative wave in the superficial cortical layers and a positive wave in the deeper cortical layers (sN-dP wave). After 1 week, the sN-dP wave was preceded by a small wave which was positive in the superficial cortical layers and negative in the deeper cortical layers (sP-dN wave). As animals grew older, the sP-dN wave became dominant over the sN-dP wave to take an adult-like configuration of responses at 3 to 4 weeks of age. The sN-dP wave was separable from the preceding sP-dN wave by double shock stimulation at a certain time interval. Therefore, these two wave components are presumably mediated by two different types of thalamocortical projections. The level of potential reversal in each wave component shifted from the deeper cortical layers to the more superficial cortical layers during maturation. The latency of the response decreased sharply from 44 msec at birth to 11 msec by 3 weeks, and thereafter gradually to 5 msec in adulthood.


Detection of esophageal varices in liver cirrhosis using non-invasive parameters.
recent guidelines recommend that all cirrhotic patients without previous variceal hemorrhage undergo endoscopic screening to detect esophageal varices. The aim of this study is to evaluate clinical, laboratory and ultrasound parameters to detect esophageal varices. this is a cross sectional study. Fourty seven consecutive cirrhotic patients without history of variceal hemorrhage underwent upper endoscopy. Physical examination, laboratory and ultrasonography to find portal vein diameter and anterioposterior splenic measurement of each patient were also recorded. esophageal varices was detected in 36 of the 47 patients (76.6%). Using bivariate analysis we found that a platelet count of 82,000/ul (90.9% sensitivity; 41.7% specificity), portal vein diameter of 1.15 cm (75% sensitivity; 54.5% pecificity) and an anteroposterior splenic measurement of 10.3 cm (83.3% sensitivity; 63.6% specificity) were predictive factors for esophageal varices in liver cirrhosis. our data show that platelet count, portal vein diameter and anteroposterior splenic measurement can be used as non invasive parameters to detect esophageal varices in cirrhotic patients.


Automatic spike detection in EEG by a two-stage procedure based on support vector machines.
In this study, we introduce a two-stage procedure based on support vector machines for the automatic detection of epileptic spikes in a multi-channel electroencephalographic signal. In the first stage, a modified non-linear digital filter is used as a pre-classifier to classify the peaks into two subgroups: (i) spikes and spike like non-spikes (ii) trivial non-spikes. The pre-classification done in the first stage not only reduces the computation time but also increases the overall detection performance of the procedure. In the second stage, the peaks falling into the first group are aimed to be separated from each other by a support vector machine that would function as a post-classifier. Visual evaluation, by two experts, of 19 channel EEG records of 7 epileptic patients showed that the best performance is obtained providing 90.3% sensitivity, 88.1% selectivity and 9.5% false detection rate.


Preparation and characterization of the micelle-forming polymeric drug indomethacin-incorporated poly(ethylene oxide)-poly(beta-benzyl L-aspartate) block copolymer micelles.
To estimate the feasibility of novel containers for drugs, poly(ethylene oxide)-poly(beta-benzyl L-aspartate) (PEO-PBLA) micelles were prepared by dialysis against water using different solvents. The solvent selected is very important because it drastically affects the stability of polymeric micelles. The critical micelle concentration (cmc) of the prepared micelles in distilled water was determined by a fluorescence probe technique using pyrene. Indomethacin (IMC) as a model drug was incorporated into the micelles by dialysis and an oil/water emulsion method. Characteristics of PEO-PBLA micelles without and with the physically trapped IMC in the inner core of the micelles (IMC/PEO-PBLA) were studied by dynamic light scattering and gel permeation chromatography/HPLC as well as an in vitro release test of IMC from the micelles. For the PEO-PBLA block copolymers, N,N-dimethylacetamide (DMAc) was found to be the best of the solvents tested to form stable polymeric micelles with a narrow size distribution and avoid its aggregation, and the cmc of PEO-PBLA micelles thus prepared was determined to be ca. 18 mg/L in water. The diameters of PEO-PBLA micelles and IMC/PEO-PBLA micelles in number averaged scale were observed to be ca. 19 and 25-29 nm, respectively. The release study of IMC from IMC/PEO-PBLA micelles in various buffer solutions at the pH range from 1.2 to 7.4 at 37 degrees C revealed that the release rate of IMC from the micelles was increased by increasing the pH of the medium and indicated that the release rate of IMC from the micelles are controlled by the partition coefficient of IMC based on the pH of the medium and interaction between IMC and the hydrophobic portion of the micelles.


Sequential synthesis of small capped RNA transcripts in vitro by vesicular stomatitis virus.
Using purified viral or intracellular transcriptive complexes (RNP cores) of vesicular stomatitis virus (VSV), we have identified several small RNA species, ranging in size from 12 to 47 nucleotides in length that are synthesized in vitro by the genomic RNA. One group of small RNA transcripts is composed of three species that are capped at their 5' termini. Two of the capped species are from the start of the N gene and one is from the start of the NS gene. Unlike the previously described 5' triphosphated small RNAs, the templates encoding these small capped RNAs had uv target sizes greater than their respective lengths. In addition, these RNAs appeared sequentially during synchronized in vitro transcription reactions. Thus, these results provide evidence that sequences representing the 5'-capped termini of N and NS mRNAs are synthesized concomitantly with their respective mRNAs rather than simultaneously at the onset of transcription as proposed for the multiple entry, start-stop model (D. Testa, P. K. Chanda, and A. K. Banerjee, 1980, Cell 21, pp. 267-275). Together with the inability of the internally initiated 5'-triphosphated RNAs to be chased into mRNA (R. A. Lazzarini, I. Chien, F. Yang, and J. D. Keene, 1982, J. Gen. Virol. 58, 429-441), these results support a single entry model of VSV mRNA transcription.


[A Case of Lung Adenocarcinoma Presenting with Leptomeningeal Carcinomatosis Successfully Treated with Afatinib after Erlotinib-Induced Hepatotoxicity].
A 65-year-old man was diagnosed with leptomeningeal carcinomatosis based on the findings of cerebrospinal fluid cytology and magnetic resonance imaging(MRI).Treatment with erlotinib and bevacizumab was initiated, and partial improvement in consciousness and MRI findings were obtained.However, it was difficult to continue the treatment because of elevation in levels of liver enzymes and melena.We switched the treatment to afatinib monotherapy, and his consciousness improved immediately.Progression -free survival and overall survival from the initiation of the treatment with afatinib were 7 and 9.4 months, respectively. This clinical course suggests activity of afatinib for central nervous system lesions of EGFRmutated lung cancer.


[The research for magnetic attachments producing static magnetic fields to influence on cytoskeletons of human periodontal ligament cells].
The present research aimed to investigate that the static magnetic field (SMF) generated by dental magnetic attachments influenced on the cytoskeletons of human periodontal ligament cells (HPDLCs). In vitro cultured HPDLCs were exposed to 10 mT and 120 mT SMF which simulated those of from the closed-field and open-field magnetic attachments respectively for 12-60 hours in a cellular SMF exposure system. The control group cells were cultured outside the SMF exposure system and were only exposed to geomagnetic field of about 0.03-0.07 mT. After finishing the SMF exposure, the cytoskeletons were observed under a laser scanning confocal microscope (LSCM). The image analysis software was utilized to measure and analyze the cell area, length/width ratios and the contents of F-actin of cells. There were certain changes observed in the cytoskeletons after HPDLCs exposed to 10 mT and 120 mT SMF for 12-60 hours. With the SMF strength increasing and the loading time extending, the cell microfilaments got ashorened change and a disordered arrangement inside cells, and the length/width ratios of cells decreased (P < 0.05). The areas of cells decreased after SMF loading for 60 hours (P < 0.05). The cell F-actin contents decreased after SMF loading for 12 hours (P < 0.05), but in the meantime there was no significant difference happening between the 36 or 60 hours SMF loading group and the control group (P > 0.05). In this study the SMF of magnetic attachments can lead the certain changes to the cytoskeletons in HPDLCs.


Complete atresia of coronary ostia in pulmonary atresia and intact ventricular septum.
We describe the clinical course, echocardiography, angiography, and histopathology of a female infant with pulmonary atresia and intact ventricular septum (PA/IVS) with complete coronary ostial atresia and right ventricle-dependent coronary circulation who survived for 7 weeks after palliative surgery. The patient expired from myocardial insufficiency while waiting for a donor heart. Postmortem examination demonstrated atretic coronary ostia, ventricular sinusoids, and myocardial infarctions of various ages. This report suggests that neonates with PA/IVS who have this extreme form of coronary abnormality may potentially be managed medically and surgically until cardiac transplantation is available.


Simultaneous screening for three correlated lipids in the VA HDL Intervention Trial.
We developed methodology to design the multistage lipid screen for the VA HDL Intervention Trial, a randomized double-blind placebo-controlled secondary prevention clinical trial of 2531 participants. The trial aimed to determine if HDL-raising therapy reduces coronary events in men with low HDL-cholesterol and desirable LDL-cholesterol. Joint lipid distributions for HDL-cholesterol, LDL-cholesterol, and triglycerides were derived on the basis of estimates from previous studies, and simulations were performed to determine the cutpoints for excluding screenees for the three lipid parameters to be used at each recruitment stage. Operating characteristics for different screening rules are presented. Comparisons between the predicted and actual study recruitment results show good agreement in lipid characteristics and underscore the complexity of simultaneously screening on correlated continuous physiologic parameters such as lipids.


Use of a strontium-enriched calcium phosphate cement in accelerating the healing of soft-tissue tendon graft within the bone tunnel in a rabbit model of anterior cruciate ligament reconstruction.
We investigated whether strontium-enriched calcium phosphate cement (Sr-CPC)-treated soft-tissue tendon graft results in accelerated healing within the bone tunnel in reconstruction of the anterior cruciate ligament (ACL). A total of 30 single-bundle ACL reconstructions using tendo Achillis allograft were performed in 15 rabbits. The graft on the tested limb was treated with Sr-CPC, whereas that on the contralateral limb was untreated and served as a control. At timepoints three, six, nine, 12 and 24 weeks after surgery, three animals were killed for histological examination. At six weeks, the graft-bone interface in the control group was filled in with fibrovascular tissue. However, the gap in the Sr-CPC group had already been completely filled in with new bone, and there was evidence of the early formation of Sharpey fibres. At 24 weeks, remodelling into a normal ACL-bone-like insertion was found in the Sr-CPC group. Coating of Sr-CPC on soft tissue tendon allograft leads to accelerated graft healing within the bone tunnel in a rabbit model of ACL reconstruction using Achilles tendon allograft.


Erratum.
In the News & Comment article "Court rejects Rifkin in biotech cases" by Mark Crawford (9 Jan., p. 159), the Food and Drug Administration (FDA) was incorrectly portrayed as having abandoned biotechnology guidelines issued by the Biotechnology Science Coordinating Committee. The agency continues to endorse the guidelines, but notes they "do not have specific regulatory significance for FDA."


Associateships: a business wedding.
The high price of being competitive may make associateships an attractive option to solo practice. Advantages of hiring an associate, factors to consider in interviewing and determining compensation are discussed.


Relation between liver fat content and the rate of VLDL apolipoprotein B-100 synthesis in children with protein-energy malnutrition.
Fatty infiltration of the liver is associated with an increased morbidity and mortality in children with severe protein-energy malnutrition (PEM), but its pathogenesis remains unclear. Although impaired synthesis of VLDL apolipoprotein B-100 (VLDL-apo B-100) is generally accepted as the pathogenetic mechanism, the rate of it synthesis has not been measured in children with PEM. The objective of the study was to ascertain the relation between the degree of hepatic steatosis and the rate of VLDL-apo B-100 synthesis in children with PEM. The fractional and absolute rates of VLDL-apo B-100 synthesis were measured with a prime-constant intravenous infusion of [2H3]leucine in 13 severely malnourished children (8 boys and 5 girls) aged 7-18 mo. Hepatic fat content was estimated by computerized tomography scanning by using the ratio of liver to spleen (L:S) attenuation. The ratio is inversely related to hepatic fat content such that the lower the L:S, the greater the amount of fat in the liver. There were significant inverse relations between L:S attenuation and VLDL-apo B-100 concentration (P < 0.02), the absolute rate of VLDL-apo B-100 synthesis (P < 0.02), and plasma triacylglycerol (P < 0.02) and serum cholesterol (P < 0.05) concentrations. These results suggest that children with PEM synthesize VLDL-apo B-100 at a faster rate as the degree of hepatic fat infiltration increases. Thus, fatty infiltration of the liver in PEM is not due to a reduction in the synthesis of VLDL-apo B-100.


The influence of covalently linked and free polyethylene glycol on the structural and release properties of rhBMP-2 loaded microspheres.
The current clinical success of therapies with recombinant human Bone Morphogenetic Protein 2 (rhBMP-2) is limited due to inefficient delivery. The high doses applied have frequently been related to severe adverse effects such as tissue swelling, seroma, inflammatory effects and heterotopic ossification. The controlled delivery of lower doses is supposed to reduce adverse effect incidence as well as costs. In this study, novel polyethylene glycol-poly(lactic-co-glycolic acid) (PEG-PLGA) diblock copolymers were used to produce low dose controlled delivery vehicles for rhBMP-2. A method to fabricate a variety of microsphere formulations with a high encapsulation efficiency in high yields was developed. The influence of PEG as an inner phase cosolvent and linked PLGA as copolymer was investigated. Six different microsphere systems with varying PEG amounts in both core and shell were characterised thoroughly with respect to the specific properties of rhBMP-2. The particle size of the microspheres was investigated with both laser diffraction and environmental scanning electron microscopy. Higher PEG/PLGA ratios showed a tendency to increase in size and a wider distribution. Due to the low rhBMP-2 doses, a profound characterisation was very challenging. The growth factor was covalently attached to rhodamine B for the first time. Studies on drug distribution in the microspheres were performed by means of confocal laser scanning microscopy. The addition of PEG to the inner phase was found to impair the formation of spherical microdomains with localized higher growth factor concentrations. Release profiles, determined with ELISA, were linked to the structural changes that were monitored. Distinct, controlled release profiles were achieved in all formulations and showed that PEG is a versatile tool in the effective control of release rates from microspheres. Higher PEG/PLGA ratios in the polymer were shown to increase the release rate from the microspheres. In contrast, PEG administered to the inner phase decreased the release rate. The biological activity of released protein was shown in vitro in an alkaline phosphatase assay. It was demonstrated that PEG-PLGA microspheres are a promising sustained delivery system which allows a reduction of the required rhBMP-2 dose to limit both adverse effects and costs. Furthermore, the data indicated that the use of PEG as an inner phase cosolvent is not suitable for rhBMP-2 in contrast the reported beneficial effects for other growth factors.


Post-transplant recurrence of atypical hemolytic uremic syndrome in a patient with thrombomodulin mutation.
HUS is characterized by hemolytic anemia, thrombocytopenia, and acute renal failure. While "typical" HUS is usually associated with Shiga toxin-producing Escherichia coli infections and recovers in the majority of cases, aHUS is caused by mutations of complement components or antibodies against CFH leading to uncontrolled activation of alternative complement pathway and often to ESRD. Recently, THBD gene mutations have been reported in aHUS. Theoretically, the risk of disease recurrence after renal transplantation should be low because THBD is primarily a membrane-bound protein expressed by endothelial cells; however, a small proportion of THBD is present as a soluble form in plasma. We report the case of a 19-yr-old man with aHUS secondary to a THBD mutation that relapsed twice after two renal transplantations performed 12 yr apart. Despite successful control of HUS with plasma exchange and eculizumab after the second transplantation, the graft was ultimately lost due to severe steroid-resistant cellular rejection. The present report suggests that THBD mutations may favor-relapse of aHUS after renal transplantation.


Mammographic changes following reduction mammaplasty.
Mammographic findings after reduction mammaplasty may be similar to those seen with carcinoma. A knowledge of the expected mammographic alterations would be helpful in differentiating postoperative changes from those seen with carcinoma of the breast. Accordingly, the clinical records and mammograms of patients who underwent reduction mammaplasty at the Dartmouth-Hitchcock Medical Center between March of 1977 and July of 1985 were analyzed. Forty-two patients had at least one mammographic examination following reduction mammaplasty. Periareolar soft-tissue changes and inferior pole alterations were present in almost all examinations of patients during the first 6 months after operation, but they decreased during the next few years. Asymmetrical densities were present in approximately half the patients throughout the follow-up period but decreased in degree. Parenchymal calcifications occurred later; few x-rays showed these calcifications during the first year, but 50 percent were apparent after 2 years. Evidence of fat necrosis occurred in approximately 10 percent. Four patients had biopsies for suspicious densities. Chronic inflammation and inclusion cyst were reported. We believe that changes after reduction mammaplasty are predictable and can usually be differentiated from those associated with cancer.


Population genetic studies on the tetrameric short tandem repeat loci D3S1358, VWA, FGA, D8S1179, D21S11, D18S51, D5S818, D13S317 and D7S820 in Egypt.
The short tandem repeat loci (STRs) D3S1358, VWA, FGA, D8S1179, D21S11, D18S51, D5S818, D13S317, D7S820 and a locus allowing for sex-discrimination (amelogenin) can be co-amplified by the polymerase chain reaction using a commercially available kit (AmpFlSTR Profiler plus, Perkin-Elmer Biosystems, San Jose, CA) and subsequently typed using capillary electrophoresis (ABI Prism 310 Genetic analyzer, Perkin Elmer Applied Biosystems, San Jose CA). To establish databases for these loci for an Arab population sample from Egypt, 140 unrelated persons were typed. Analysis of these data revealed that all loci except for VWA were in Hardy-Weinberg equilibrium, that the combined mean paternity exclusion chance (MEC) was 0.999875 and that the combined discriminating power (DP) was 2.635 x 10(-11). The allelic distributions found in the Egyptian sample were significantly different at four loci from those found for an Austrian Caucasian population, at all nine loci from an African-American sample and at six of six loci from a Chinese sample. No evidence of linkage equilibrium between any of the co-amplified loci was found. Our results support that the combination of multiplex PCR and capillary electrophoresis can both save time and yield excellent results for paternity testing and stain analysis.


Diagnostic study of four-wave-mixing-based electric-field measurements in high-pressure nitrogen plasmas.
We present the results of a diagnostic study of the use of coherent four wave mixing for in situ measurement of an electric field in air or in nitrogen-containing plasmas. Static electric fields in air at a nominal pressure of 625 Torr and temperature of 300 K are detected using vibrational CARS of nitrogen. It is shown that the ratio of the infrared signal to the vibrational N(2) CARS signal is equal to approximately 10(-8) at 8.33 kV/cm, a factor of approximately 50 less than that predicted assuming equal third-order nonlinear susceptibilities. It is also shown that the spatial resolution of a typical collinear geometry measurement is approximately 1 cm. Finally, it is shown that achieving sensitivities of the order of 1 kV/cm requires that the coherent Raman pumping be performed in the highly saturated and Stark broadened regime.


Cloning and characterization of a novel amidase from Paracoccus sp. M-1, showing aryl acylamidase and acyl transferase activities.
A novel amidase gene, designated pamh, was cloned from Paracoccus sp. M-1. Site-directed mutagenesis and bioinformatic analysis showed that the PamH protein belonged to the amidase signature enzyme family. PamH was expressed in Escherichia coli, purified, and characterized. The molecular mass of PamH was determined to be 52 kDa with an isoelectric point of 5.13. PamH displayed its highest enzymatic activity at 45°C and at pH 8.0 and was stable within a pH range of 5.0-10.0. The PamH enzyme exhibited amidase activity, aryl acylamidase activity, and acyl transferase activity, allowing it to function across a very broad substrate spectrum. PamH was highly active on aromatic and short-chain aliphatic amides (benzamide and propionamide), moderately active on amino acid amides, and possessed weak urease activity. Of the anilides examined, only propanil was a good substrate for PamH. For propanil, the k (cat) and K (m) were 2.8 s(-1) and 158 μM, respectively, and the catalytic efficiency value (k (cat)/K (m)) was 0.018 μM(-1) s(-1). In addition, PamH was able to catalyze the acyl transfer reaction to hydroxylamine for both amide and anilide substrates, including acetamide, propanil, and 4-nitroacetanilide; the highest reaction rate was shown with isobutyramide. These characteristics make PamH an excellent candidate for environmental remediation and an important enzyme for the biosynthesis of novel amides.


Does Glycemic Control Modulate the Impairment of NLRP3 Inflammasome Activation in Type 2 Diabetes?
Since mitochondrial dysfunction is associated with NOD-like receptor family protein 3 (NLRP3) activation in type 2 diabetes (T2D), which can eventually lead to an impaired immune response, we set out to determine if glycemic control modulates the effects of T2D on the NLRP3 inflammasome. We have studied leukocytes from 61 diabetic patients [25 with glycated hemoglobin (HbA1c) ≤7% and 36 with HbA1c ≥8%] and 40 healthy controls. Total and mitochondrial reactive oxygen species (ROS) production was enhanced in T2D patients, and mitochondrial ROS was more pronounced in those with poor glycemic control. Levels of gene and protein expression of NLRP3 were decreased in both diabetic groups and more so in those with HbA1c ≥8%. In addition, there was a decrease in gene expression and serum concentrations of interleukin (IL)-1β, IL-12, and caspase-1 in line with inhibition of the NLRP3 inflammasome. Our data also suggest negative correlations between HbA1c levels and NLRP3 protein expression, serum levels of IL-12 and IL-1β, and caspase-1 messenger RNA expression. Our findings lead us to raise the hypothesis of an association between poor glycemic control in T2D and an impairment of the NLRP3 inflammasome, suggesting that glycemic control plays an important role in the immune response of diabetic subjects.


Carcinogenesis induced by UVA (365-nm) radiation: the dose-time dependence of tumor formation in hairless mice.
Although ultraviolet B (UVB wavelengths 280-315 nm) dominates the carcinogenic effect of sunlight, ultraviolet A (UVA 315-400 nm) is estimated to contribute 10-20% to the carcinogenic dose; a substantial background that is not affected by a depletion of the ozone layer. Furthermore, certain high-power modern tanning lamps emit mainly long wave UVA (UVA1; 340-400 nm). For a proper risk estimate of UVA exposure its carcinogenicity relative to that of UVB exposure needs to be determined more accurately. To this end we determined the dose-time relationship for skin tumor induction in hairless mice that were irradiated daily with custom-made Philips 365-nm sources. Irradiation of the group exposed to the highest of the four daily doses (430, 240, 140 and 75 kJ/m2) had to be discontinued because severe scratching set in after 3 months (no tumors). In the lower dose-groups the prevalence curves for skin carcinomas (percentage of tumor-bearing mice versus logarithm of time) ran virtually parallel, and were similar to those found with daily UVB exposure. However, the relationship between the daily dose (D) and the median tumor induction time (t50) appeared to differ: with UVB we found that t50 D(r) = constant, with r = 0.6, whereas with UVA1 we found r approximately 0.4. This would imply that 365-nm carcinogenesis shows less of a dose-dependency than UVB carcinogenesis, and that 365-nm radiation becomes more carcinogenic, relative to UVB, as the daily doses are lowered. This relative shift at low doses complicates extrapolation of UVB to UVA risks in humans. Based on the t50 from the lowest dose-group we found that the carcinogenicity at 365 nm (per J/m2) is 0.9 x 10(-4) times that at 293 nm, the wavelength of maximum carcinogenicity in hairless mice. This result for 365-nm carcinogenicity falls well within the margins of error of the wavelength dependency that was estimated earlier from experiments with broadband UV sources.


Fish-Bone Impaction of the Throat.
A series of 55 cases of fish-bone impaction of the pharynx and œsophagus is discussed. Special reference is made to the serious and sometimes fatal complications that may result from delay in treatment, and cases illustrating these complications are reported in detail. Fifty-five cases of fish-bone impaction of the pharynx and the œsophagus are reported. Spontaneous disimpaction can occur. Persistent simple impaction, although distressing for the patient, is easily managed. Delay in treatment or well-intentioned but inexpert attempts at dislodging the fish bone by the patient or his friends may result in perforation of the pharyngo-œsophageal wall with retropharyngeal inflammation and suppuration, a condition carrying high morbidity. Perforation of the carotid artery or the aorta is a grave complication, requiring urgent treatment if a high mortality is to be avoided. A brief review is made of the complications of fish-bone impaction in the abdominal part of the alimentary tract.


Genotyping of chloroquine resistant Plasmodium falciparum in wild caught Anopheles minimus mosquitoes in a malaria endemic area of Assam, India.
We validated the feasibility of using Plasmodium falciparum, the human malaria parasite, DNA present in wild caught vector mosquitoes for the characterization of chloroquine resistance status. House frequenting mosquitoes belonging to Anopheles minimus complex were collected from human dwellings in a malaria endemic area of Assam, Northeast India and DNA was extracted from the head-thorax region of individual mosquitoes. Anopheles minimus complex mosquitoes were identified to species level and screened for the presence of Plasmodium sp. using molecular tools. Nested PCR-RFLP method was used for genotyping of P. falciparum based on K76T mutation in the chloroquine resistance transporter (pfcrt) gene. Three of the 27 wild caught An. minimus mosquitoes were harbouring P. falciparum sporozoites (positivity 11.1%) and all 3 were had 76T mutation in the pfcrt gene, indicating chloroquine resistance. The approach of characterizing antimalarial resistance of malaria parasite in vector mosquitoes can potentially be used as a surveillance tool for monitoring transmission of antimalarial drug resistant parasite strains in the community.


Full-term gestation and transvaginal delivery after wide resection of an abdominal desmoid tumor during pregnancy.
A 29-year-old female was diagnosed with a symptomatic, extra-abdominal desmoid tumor during the first trimester of pregnancy. Computerized tomography (CT) and transabdominal ultrasound (US) noted a mass within the left rectus sheath measuring up to 15 cm in greatest diameter, with mild compression of the uterus. Preoperative diagnosis was confirmed by core-needle biopsy of the lesion. At 20-weeks gestation, wide local resection of the tumor with disease-free margins, as well as abdominal wall reconstruction with polytetrafluoroethylene (PTFE) mesh was successfully undertaken. Histological examination of the tumor ex vivo confirmed that the lesion was a desmoid tumor consisting of spindle cells with dense infiltrating collagenous fibers. Subsequent to her resection, the patient completed a full-term pregnancy without complication, and proceeded with a complication-free transvaginal delivery at 39 weeks. This case illustrates the probable contribution of estrogens towards desmoid tumor development, the durability of abdominal wall reconstruction when subjected to the extraordinary strain of both a gravid uterus and labor, as well as the safety and efficacy of aggressive surgical therapy during pregnancy.


[Neurobiology and pharmacotherapy of obsessive-compulsive disorder].
Obsessive-compulsive disorder belongs to anxiety disorders, with a prevalence of 2,5% in the general population. The pathogeny of the disorder includes a probable genetic component but of moderate importance. Neuroimaging studies showed a hyperactivity of the prefrontal cortex and the caudate nucleus which appears to reflect abnormalities in cerebral circuits. The pharmacological treatment of obsessive-compulsive disorder comprises in first line selective serotonin reuptake blocker antidepressants. Clomipramine (Anafranil), often considered as more effective represents a second choice due to its side-effects. The treatment generally requires high doses of antidepressants administered over a prolonged period. Several augmentation strategies have been proposed for resistant patients. Very recently, brain neurostimulation techniques using implanted electrodes have demonstrated their interest in case of failure of other treatment strategies.


Urogenital and vasomotor symptoms in relation to menopausal status and the use of hormone replacement therapy (HRT) in healthy women during transition to menopause.
To investigate the relationship between climacteric status, hormonal levels, vasomotor symptoms, vaginal dryness and urinary incontinence in a cohort of healthy women during transition to menopause, and further to evaluate the effects of hormone replacement therapy on these symptoms. A total of 147 women were followed for 4 years during transition to menopause. They were all 49 years old when entering the study. Each annual visit included a general health screening, gynecological examination and blood sampling. The subjects were questioned about sociodemographic background, obstetric and gynecological history and they kept bleeding diary cards. Urinary incontinence was reported by 57% at the first visit and decreased to 34% at the last visit. No correlation to hormonal levels or to the use of HRT (hormone replacement therapy) was seen, but parity was significantly (P = 0.05) correlated to urinary incontinence. Vaginal dryness occurred in 37% at the first visit. Vaginal dryness was experienced by 1/3 of the premenopausal women. Vasomotor symptoms were reported by 56% at the first visit and were associated with high levels of FSH and LH (P < 0.001 and P = 0.002, respectively). One third of premenopausal women reported on vasomotor symptoms. Hormone replacement therapy did not relieve hot flushes in these women. Urogenital and vasomotor symptoms experienced by premenopausal women do not seem to be relieved by hormone replacement therapy.


NO mediates gastric relaxation after brief vagal stimulation in anesthetized dogs.
In vitro studies showed that relaxations induced after vagal stimulation of the guinea pig stomach are mediated via nitric oxide (NO). The role of NO in canine gastric relaxation in response to vagal stimulation has as yet not been studied. The present study examined the influence of NG-nitro-L-arginine (L-NNA) on gastric relaxations after vagal nerve stimulation in the anesthetized dog. In beagle dogs (n = 7), the ventral and dorsal abdominal vagal nerves were connected to a pair of platinum electrodes. Gastric tone was measured by means of a barostat. Changes in gastric motility were measured with force transducers sutured on the fundus and the antrum. The cervical vagi were sectioned, and dogs were given atropine (0.2 mg/kg i.v.) and guanethidine (5 mg/kg i.v.). Electrical stimulation of the vagal trunks (19 V, 1-ms duration, for 15 s every 2 min, 1-30 Hz) induced frequency-dependent increases in volume. On the fundus, frequency-dependent relaxations could be observed (maximal effect at 5 mmHg and at 10 Hz). During electrical stimulation, the spontaneous antral contractions were completely blocked. After cessation of the stimulus, "rebound" contractions could be observed. L-NNA (5 mg/kg i.v.) completely blocked the increases in gastric volume and the relaxations on the fundus. On the antrum, however, contractions were observed during the electrical stimulation. L-Arginine (250 mg/kg i.v.) gradually restored the relaxations on electrical stimulation. This study demonstrates that NO mediates short-lasting vagally induced gastric relaxations in the anesthetized dog.


Persulfate activation by naturally occurring trace minerals.
The potential for 13 naturally occurring minerals to mediate the decomposition of persulfate and generate a range of reactive oxygen species was investigated to provide fundamental information on activation mechanisms when persulfate is used for in situ chemical oxidation (ISCO). Only four of the minerals (cobaltite, ilmenite, pyrite, and siderite) promoted the decomposition of persulfate more rapidly than persulfate-deionized water control systems. The other nine minerals decomposed persulfate at the same rate or more slowly than the control systems. Mineral-mediated persulfate activation was conducted with the addition of one of three probe compounds to detect the generation of reactive oxygen species: anisole (sulfate+hydroxyl radical), nitrobenzene (hydroxyl radical), and hexachloroethane (reductants and nucleophiles). The reduced mineral pyrite promoted rapid generation of sulfate+hydroxyl radical. However, the remainder of the minerals provided minimal potential for the generation of reactive oxygen species. The results of this research demonstrate that the majority of naturally occurring trace minerals do not activate persulfate to generate reactive oxygen species, and other mechanisms of activation are necessary to promote contaminant destruction in the subsurface during persulfate ISCO.


Structural investigations into microtubule-MAP complexes.
Microtubules interact with a large variety of factors commonly referred to as either molecular motors (kinesins, dyneins) or structural microtubule-associated proteins (MAPs). MAPs do not exhibit motor activity, but regulate microtubule dynamics and their interactions with molecular motors, and organelles such as kinetochores or centrosomes. Structural investigations into microtubule-kinesin motor complexes are quite advanced today and by helical three-dimensional (3-D) analysis reveal a resolution of the motor-tubulin interface at <1.0 nm. However, due to their flexible structure MAPs like tau or MAP2C cannot be visualized in the same straightforward manner. Helical averaging usually reveals only the location of strong binding sites while the overall structure of the MAP remains unsolved. Other MAPs such as EB1 bind very selectively only to some parts of the microtubule lattice such as the lattice seam. Thus, they do not reveal a stoichiometric tubulin:MAP-binding ratio that would allow for a quantitative helical 3-D analysis. Therefore, to get a better view on the structure of microtubule-MAP complexes we often used a strategy that combined cryo-electron microscopy and helical or tomographic 3-D analysis with freeze-drying and high-resolution unidirectional surface shadowing. 3-D analysis of ice-embedded specimens reveals their full 3-D volume. This relies either on a repetitive structure following a helical symmetry that can be used for averaging or suffers from the limited resolution that is currently achievable with cryotomography. Surface metal shadowing exclusively images surface-exposed features at very high contrast, adding highly valuable information to 2-D or 3-D data of vitrified structures.


An exploration of negative thoughts as a normal phenomenon after childbirth.
The period following the birth of a child brings many transitions into a woman's life, which can effect major psychological and social changes, including feelings of loss. If new mothers experience negative thoughts at this time, when societal expectations are of happiness, this may lead to feelings of unacceptability and guilt. This study aimed to investigate the prevalence of negative thoughts after childbirth in nondepressed mothers. Following the identification of negative thoughts experienced by women who had suffered postnatal depression, a quantitative survey was conducted, which asked nondepressed mothers to indicate how often they experienced the negative thoughts or images identified by depressed mothers. One hundred and fifty-eight returned questionnaire packs were included in the analyses. The 158 nondepressed mothers acknowledged experiencing all but one of the 54 negative cognitions. Negative cognitions usually associated with postnatal depression are also experienced by mothers who are not considered depressed. This information provides evidence for reassuring new mothers that negative thoughts after childbirth are common. This, in turn, may help to reduce feelings of guilt associated with experiencing negative thoughts in the postpartum period.


Current approaches to helping children cope with a parent's terminal illness.
Much has been learned about childhood bereavement in the last few decades as studies have increasingly focused on the direct interviewing of children about their recovery from the tragic loss of a parent. It has been shown that children do indeed mourn, although differently from adults. Important moderating and mediating variables have been identified that impact their recovery from the loss of a parent, which can be the focus of intervention. When death is expected, the terminal phase of an illness has been found to be particularly stressful for children, yet seldom investigated. Similarly, few studies have explored the impact of development on children's experience and expression of grief. We present research findings that clarify phases in children's experience during the terminal illness, hospital visits, the death, and its immediate aftermath, as well as how the parent is mourned and issues in longer term reconstitution. Variations in children's responses in these phases are described as they were experienced by 87 children from 3 different developmental groupings: 3 to 5 years, 6 to 8 years, and 9 to 11 years. Recommendations are suggested for parents and professionals about ways to understand and support children during the terminal illness, at the time of death, and during the phase of reconstitution.


Structural and metabolic changes in the brain of patients with upper motor neuron disorders: a multiparametric MRI study.
Our objective was to assess and compare the diagnostic sensitivity of conventional MRI (cMRI), magnetization transfer imaging (MTI), diffusion-weighted imaging (DWI), and proton magnetic resonance spectroscopic imaging ((1)H-MRSI) in patients with amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS). Thirty-eight ALS patients, nine PLS patients, and 22 healthy controls were enrolled. cMRI, MTI, DWI and (1)H-MRSI were obtained. ALS patients were classified as advanced phase (Ap)-ALS (definite+probable) and early phase (Ep)-ALS (possible+probable-laboratory supported). cMRI was highly sensitive in detecting corticospinal tract (CST) hyperintensities in Ap-ALS (63.4%) and PLS (71.9%), but it was poorly sensitive in Ep-ALS (17.1%). Hyperintensity on proton density-weighted images correlated with ALS severity (p=0.02). CST apparent diffusion coefficient was significantly increased in ALS (p<0.01) and PLS (p=0.02) versus controls. The N-acetylaspartate/creatine ratio was significantly reduced in the motor cortex of patients versus controls (p< or = 0.01 in PLS, p=0.02 in Ap-ALS). The study shows the utility of cMRI for diagnosing ALS. Nevertheless, MRI sensitivity is limited at the early stages of the disease. In these cases, DWI and (1)H-MRSI seem to have the potential to ameliorate the patients' work-up and estimate the nature and extent of the underlying pathological damage.


High-dose methotrexate in pediatric acute lymphoblastic leukemia: impact of ABCC2 polymorphisms on plasma concentrations.
The adenosine triphosphate-binding cassette (ABC) class transporter ABCC2 (MRP2 [multidrug resistance related protein 2] or cMOAT [canalicular multispecific organic anion transporter]) is involved in the cellular outward transport and elimination of methotrexate. We hypothesized that common genetic variations may contribute to the variability of high-dose methotrexate pharmacokinetics. Polymorphisms in all 32 exons of the ABCC2 gene were analyzed in a reference group of 59 healthy white subjects by polymerase chain reaction, single-strand conformation polymorphism, and sequencing. Subsequently, we assessed the association of polymorphisms with the methotrexate plasma concentrations in 44 pediatric patients with acute lymphoblastic leukemia (ALL) (29 male and 15 female patients; mean age, 6.8+/-4.8 years). Patients received 4 cycles of 5000 mg/m2 body surface area according to the ALL-Berlin-Frankfurt-Muenster (BFM) 95 or ALL-BFM 2000 protocol. In the reference group we detected 8 frequent single-nucleotide polymorphisms. Five of these were in complete linkage disequilibrium. Overall, 5 new polymorphisms are described. The genotype distribution of the patient cohort was not significantly different from the reference collective. The mean plasma methotrexate area under the curve from 36 to 48 hours after the start of the infusion was significantly 2-fold higher in female patients carrying at least 1 -24T allele as compared with all other patients (14.2+/-12.8 h.micromol/L versus 6.9+/-4.2 h.micromol/L, P<.001). The risk to have 2 or more cycles necessitating an intensification of folinate rescue was 9-fold (95% confidence interval, 1.8- to 44-fold) in female patients carrying at least 1 T allele (P=.0067). The data suggest a hitherto unknown gender-specific impact of the -24C>T ABCC2 gene polymorphism on high-dose methotrexate pharmacokinetics. Whereas a nonfunctional MRP2 variant has been described in a patient with severe impairment of methotrexate excretion, our study is the first to suggest that a frequent ABCC2 polymorphism contributes to variability of methotrexate kinetics.


Generation of induced pluripotent stem cells from skin fibroblasts of a patient with olivopontocerebellar atrophy.
Generation of induced pluripotent stem (iPS) cells from somatic cells of patients represents a powerful tool for disease modeling, and they may have a wide range of applications in cell therapies. Olivopontocerebellar atrophy (OPCA) is a rare and debilitating neurologic disease of insidious onset, characterized by atrophy of the cerebellum pons and inferior olivary nuclei with concomitant ambulation deficits and dyscoordination. Here, we report the generation of iPS cells from skin fibroblasts of a 56-year-old female patient with familial OPCA. OPCA is classified in the autosomal dominant ataxia that is also named spinocerebellar ataxia (SCA) 7. The disease allele of SCA7 gene of the patient contains 45 CAG trinucleotide repeats, the number of which is larger than the normal repeat number (4 to 36 CAG repeats). The OPCA-iPS cells were generated via ectopic expression of four transcription factors: OCT4, SOX2, KLF4 and c-MYC. The OPCA-iPS cells expressed the pluripotency markers, and they can be differentiated into various somatic cell types in vitro and in vivo. Furthermore, the iPS cells also can be committed to differentiate into neural cells. Therefore, the OPCA-iPS cells offer an unprecedented cell model to investigate disease mechanisms, discover novel drugs, and develop new therapies for OPCA.


Active surveillance screening of MRSA and eradication of the carrier state decreases surgical-site infections caused by MRSA.
Surgical-site infections (SSI), because of MRSA, are a challenge for acute care hospitals. The current study examines the impact of best practices and active surveillance screening for MRSA on reduction of MRSA SSIs. Beginning February 2007, all admissions to a 761-bed tertiary care hospital were screened for MRSA by nasal swab using polymerase chain reaction-based testing. Positive nasal carriers of MRSA were treated before operation. The subset of patients undergoing procedures that are part of the Surgical Infection Prevention Project were followed for MRSA SSIs. SSI rates (per 100 procedures) were determined using the National Nosocomial Infection Surveillance definitions. MRSA SSI rates were compared before and after the MRSA screening intervention. Differences were analyzed using Fisher's exact test and chi-square with Yate's continuity correction. Where specimens were available, genotyping of MRSA was performed using a commercially available assay. After universal MRSA surveillance, 5,094 patients underwent Surgical Infection Prevention Project procedures. The rate of MRSA SSI decreased from 0.23% to 0.09%. The reduction was most pronounced in joint-replacement procedures (0.30% to 0%; p = 0.04). No other differences were statistically significant. Of the seven patients in whom MRSA SSI developed after universal screening, four had positive MRSA screens; none had received preoperative eradication of MRSA. In two of these patients, the genotype of MRSA detected on screening and in SSI was genetically indistinguishable. Surveillance for MRSA and eradication of the carrier state reduces the rate of MRSA SSI.


Weight reduction via life-style modifications results in reverse remodelling and cardiac functional improvement in a patient with obesity.
The prevalence of obesity has increased strikingly in recent years. Obesity is associated with increased left ventricular end-diastolic dimension (LVEDD), ventricular wall thickness, left ventricular (LV) mass, left atrial diameter, subtle myocardial systolic as well as diastolic dysfunction and has been identified as an independent predictor of these changes. It's convinced that weight reduction results in cardiac reverse remodelling, while the functional changes after weight reduction are variable. Here, we present a recent case of man with moderate obesity who acquires favourable regression in chamber size, wall thickness and significant improvement in cardiac function. Briefly, after life-style modifications and comprehensive secondary prevention, great amounts of weight loss was achieved simultaneously with decreased LVEDD and increased LV ejection fraction. As dietary intervention and regular physical activity are pivotal for these benefits, this non-invasive approach for weight loss should be advocated in selected patients.


A Pragmatic Internet Intervention to Promote Positive Parenting and School Readiness in Early Childhood: Initial Evidence of Program Use and Satisfaction.
Internet-based parenting programs have the potential to connect families to research-informed materials to promote positive child development. However, such programs can only succeed to the extent that the intended population engages with them. This study aimed to evaluate engagement in the 5-a-Day Parenting program, a technology-based program designed with low-income families in mind, to promote daily use of 5 specific parenting activities conducive to children's school readiness. Following earlier pilot data, the program was enhanced with an initial motivational e-intervention and tailored text messages designed to promote engagement. Parents were recruited from local childcare centers and through a participant registry. We examined rates of receipt of program text messages and use of video-based content on the program website, 3 factors that may affect website use, and satisfaction with key program elements. A total of 360 parents of young children learned about the study and had the opportunity to use the 5-a-Day Parenting website. Of these, 94 parents participated in the study, and 33% (31/94) accessed the video-based content on the website at least once. No association was found between website use and program recruitment approach, program-affiliation message, sociocontextual risk, and baseline use of the five parenting activities. Satisfaction with text messages and video-based content was high. For some parents, technology-based programs appear useful; however, engagement could still be enhanced. Additional research should seek innovative strategies for promoting engagement in Web-based parenting programs.


Anatomical Knowledge for the Infra-Pyloric Vein Preservation during the Laparoscopy-Assisted Pylorus-Preserving Gastrectomy.
Fine anatomical knowledge enables us to use safer laparoscopy-assisted pylorus-preserving gastrectomy (LAPPG). Detailed anatomical knowledge of the infra-pyloric vein (IPV) remains obscure. In this study, the aim was to classify the IPV vessel flow. From April 2009 to November 2012, 43 patients with clinical T1 gastric cancer underwent LAPPG with preservation of IPV. Operative videos were retrospectively reviewed, and an anatomical classification of IPV was proposed. The IPV flow came into the right gastro-epiploic vein (RGEV) and/or the anterior superior pancreaticoduodenal vein (ASPDV). The IPV anatomical flow pattern was classified according to the following 4 types: Type I, the IPV more than 2 flow into RGEV; Type IIa, only 1 IPV into RGEV without into ASPDV; Type IIb, one IPV flow into RGEV and one flow into ASPDV; Type III, IPV only into ASPDV. The proportion of each type was 39.5% (17/43) in Type I, 30.2% (13/43) in Type IIa, 14% (6/43) in Type IIb, and 16.3% (7/43) in Type III. The anatomical flow pattern of the IPV was described. It would be beneficial to improve the anatomical knowledge of the IPV for more elaborate and safer lymph node dissection during laparoscopic gastrectomy.


Unsafe to play? Neighborhood disorder and lack of safety predict reduced physical activity among urban children and adolescents.
Lack of physical activity is associated with increased risk of overweight and cardiovascular disease, conditions associated with lower socioeconomic status (SES). Associations between activity levels of urban youth and limited access to safe recreation areas in their neighborhoods of residence were investigated. Analyses of data from the Project on Human Development in Chicago Neighborhoods, a multilevel longitudinal study of families and communities, are reported. Chicago, Illinois. Individual-level data were obtained from 1378 youth 11 to 16 years old and caregivers living in 80 neighborhood clusters. Neighborhood-level data were collected from 8782 community residents and videotapes of 15,141 block faces. Parental estimates of hours youth spent in recreational programming were used to estimate physical activity. A scale of residents' assessment of neighborhood safety for children's play was created; disorder measures came from videotaped observations. Physical activity averaged 2.7 hours/week (SD = 5.0), varying significantly across neighborhoods. Using hierarchical linear regression, SES, age, and male gender, but not body mass index, were independently associated with physical activity. Lower neighborhood safety and social disorder were significantly associated with less activity, controlling for demographics. One mechanism for reduced physical activity among youth may be the influence of unsafe neighborhoods. Neighborhood interventions to increase safety and reduce disorder may be efficacious in increasing physical activity, thereby reducing risk of overweight and cardiovascular disease.


The morphogenetic triangle: a new conceptual tool for application to problems in dental morphogenesis.
A hypothetical mathematical model of human dental crown height attainment during morphogenesis was developed. The model is based on well-known histologic stages of tooth development from initiation to crown completion, with special emphasis on the dynamics and life-cycle of the cells of the inner enamel epithelium. From three temporal events (P, initiation of proliferation; D, initiation of differentiation; C, crown completion), and crown height (H) measured at the dentino-enamel junction, a morphogenetic triangle PDZ can be constructed where Z = coordinates of H and C at the time of crown completion. The slope of lines PZ and DZ represent average proliferation rate (Rp) and average differentiation rate (Rd) of the inner enamel epithelium, respectively, during crown formation. From data available in the literature, and based on morphogenetic triangle principles, Rp and Rd were calculated for the deciduous and succedaneous dentitions. A strong positive correlation between Rp and Rd was observed throughout the 20-tooth series (r = 0.996); however, Rp and Rd showed moderately strong negative associations with H, P, D, C, and the intervals between PD, PC, and DC. The smaller deciduous tooth in each deciduous:permanent pair was associated with faster Rp and Rd, and shorter intervals between initiation of proliferation, initiation of differentiation, and crown completion. The data generated in this analysis of a hypothetical dentition, while not definitive, provide new insights and a theoretical basis for a broader understanding of the basic mechanisms involved in the attainment of certain tooth dimensions during morphogenesis.


Association between the PI*M3 allele of alpha 1-antitrypsin and Alzheimer's disease? A preliminary report.
The deposition of beta A4-amyloid in senile plaques in the brain and small cerebral vessels is one of the pathological hallmarks of Alzheimer's disease (AD). Serine protease inhibitors (serpins) such as alpha 1-antitrypsin and alpha 1-antichymotrypsin have been found to be associated with beta-amyloid deposits; interest in their role in the pathogenesis of AD has therefore recently increased. We have analyzed alpha 1-antitrypsin phenotypes in a sample of 29 Polish patients with probable Alzheimer's disease. We have found an increased frequency of the PI*M3 allele (0.1897) in patients in comparison with the general population control (0.0563).


Signaling pathways involved in thyroid hyperfunction and growth in Graves' disease.
The elucidation of the multiple signaling cascades coupled to the TSH receptor has offered new approaches in the understanding of the pathogenesis of Graves' disease. Here we review findings showing that immunoglobulins from Graves' patients are heterogeneous, bind to different epitopes and, similarly to TSH, activate different signaling pathways, including adenylyl cyclase, phospholipase C and phospholipase A2. Evidence that the multiplicity of signals correlates with the different manifestations of the disease is also summarized. We believe that the dissection of the molecular mechanisms involved in the pathogenesis of Graves' disease offers the basis for developing novel therapeutical approaches to this disease.


The efficacy of various alloplastic bone grafts on the healing of rat calvarial defects.
The objective of this study was to determine the relative efficacy of currently available alloplastic bone repair materials in the healing of rat calvarial defects histologically, histomorphometrically and biochemically. A representative material was selected from six major classes of bone repair materials and placed in 4 mm diameter calvarial defects of 6-week-old male Sprague-Dawley rats (five animals in the control and each of the six experimental groups). The outcomes were assessed after 2 months for alkaline phosphatase (ALP) activity and after 4 months of healing for histomorphometry. The tested alloplastic implant materials did not significantly increase ALP activity or the amount of new bone formation in the healing of rat calvarial defects relative to controls (P > 0.05). However, when the implant material itself was included in the analysis, significant differences were observed (P < 0.05). Additionally, the tested materials varied in their ability to bridge the bony defect. These data suggest that the rate of bone formation cannot be increased beyond control levels, rather the advantage of implant materials may be in their efficiency in filling the defect through incorporation of the material into the healing site and rapidly bridging the wound.


Comparison of electron scattering algorithms in Geant4.
Electron scattering algorithms in Geant4 versions 9.4 and 9.5 were benchmarked by comparing scattered distributions against previously measured values at 13 and 20 MeV, for low, intermediate, and high atomic number materials. Several scattering models were used: Versions 93 and 95 of the Urban model, with different step size limits near boundaries; Goudsmit-Saunderson multiple scattering; and single scattering. The Urban93 and Urban95 models with a large step size limit (as in the Option 0 physics list) were found to give results most closely matching the experimental results. Scattered distributions using the Urban models were all narrower than measured by up to 6%, consistent with previous published simulations using EGSnrc. This is suggestive of a systematic difference between simulations and measurement. The magnitudes of the differences were similar to previously published results using Geant4, although there were differences in detail. In particular, the current results were typically 2% narrower than values. Results with the more restrictive step size limit in Option 3 were even more narrow, and close to those with single scattering. The Goudsmit-Saunderson multiple scattering model produced distributions up to 15% different from measured in Geant4 version 9.5 and up to 45% different in Geant4 version 9.4.


Controlled integration of selected detectors and emitters in photonic integrated circuits.
Integration of superconducting nanowire single-photon detectors and quantum sources with photonic waveguides is crucial for realizing advanced quantum integrated circuits. However, scalability is hindered by stringent requirements on high-performance detectors. Here we overcome the yield limitation by controlled coupling of photonic channels to pre-selected detectors based on measuring critical current, timing resolution, and detection efficiency. As a proof of concept of our approach, we demonstrate a hybrid on-chip full-transceiver consisting of a deterministically integrated detector coupled to a selected nanowire quantum dot through a filtering circuit made of a silicon nitride waveguide and a ring resonator filter, delivering 100 dB suppression of the excitation laser. In addition, we perform extensive testing of the detectors before and after integration in the photonic circuit and show that the high performance of the superconducting nanowire detectors, including timing jitter down to 23 ± 3 ps, is maintained. Our approach is fully compatible with wafer-level automated testing in a cleanroom environment.


Cell cycle progression and activation of Akt kinase are required for insulin-like growth factor I-mediated suppression of apoptosis in granulosa cells.
Ovarian follicle development is dependent on growth factors that stimulate cell proliferation and act as survival factors to prevent apoptosis of follicle cells. We examined the mechanism of the protective effect of IGF-I against Fas ligand-induced apoptosis of granulosa cells and its relationship to cell proliferation. IGF-I activated both the phosphoinositide 3'-OH kinase (PI3K) and the MAPK pathways. Experiments using specific inhibitors of these pathways showed that protection by IGF-I was mediated by the PI3K pathway and not the MAPK pathway. Recombinant adenoviruses were used to test whether the downstream target of PI3K activation, Akt kinase, was required for protection against apoptosis. Expression of dominant negative Akt prevented protection by IGF-I whereas expression of constitutively active Akt (myrAkt) mimicked the effect of IGF-I. Treatment with IGF-I, or expression of myrAkt, increased progression from G(0)/G(1) to S phase of the cell cycle whereas expression of dominant negative Akt inhibited G(0)/G(1) to S phase progression and prevented the stimulatory effect of IGF-I. We tested whether cell cycle progression was required for protection from apoptosis using the cyclin-dependent kinase-2 inhibitor roscovitine, which blocks cells at the G(1)/S transition. Roscovitine prevented the protective effect of IGF-I and myrAkt expression against apoptosis. Therefore, activation of Akt is not sufficient to protect granulosa cells from apoptosis in the absence of cell cycle progression. In summary, IGF-I protects granulosa cells from apoptosis by activation of the PI3K/Akt pathway. This protective effect can occur only when progression from G(1) to S phase of the cell cycle regulated by the PI3K/Akt pathway is unperturbed.


[A new method for measuring rotation of a vertebral scoliosis (author's transl)].
A new radiologic method for measuring the rotation of a scoliosis from CT pictures is described. Normal deviation from the 0 position at the level of the first lumbar vertebra in 50 patients without clinically demonstrable scoliosis when accurately positioned, was M = 0.06 degrees +/- 2.95 SD. Direct measurements of the rotation of the spine and of the displacement of the sternum permit serial observation of the progress of the scoliosis and of the consequent thoracic deformity, as well as the result of treatment.


[Anti-tumor activity of safflower polysaccharide (SPS) and effect on cytotoxicity of CTL cells, NK cells of T739 lung cancer in mice].
To study the anti-tumor activity of SPS in vivo and in vitro and the cytotoxicity of CTL cells, NK cells of T739 lung cancer in mice. The transplanted tumor model of S180 Sarcoma was established with KM mouse. The SPS was adminished i.p. for 10 d, the tumor weight was detected. The transplanted tumor model of LA795 lung cancer was established with T739 mouse and SPS was adminished i.p. for 10 d and the tumor weight and the cytotoxicity of CTL cells, NK cells were detected. The Anti-tumor activity of SPS on three types of tumor cells in vitro was observed with trypan blue exclusion staining. SPS 40 mg x kg(-1) can significantly inhibit the growth of S180 Sarcoma in mice and inhibitory rate was 51.33% (P<0.01). It can also inhibit the growth of LA795 lung cancer in mice and the tumor volume was reduced obviously for 3.29 mm3 (P<0.05). It can remarkably enhance the cytotoxicity of splenic CTL cells, NK cells in tumor-bearing (P<0.05). SPS have anti-tumor effects, the mechanism of the anti-tumor activity may be related to enhance the cytotoxicity of CTL cell and NK cell.


The Paton individual-based model legacy.
Ray Paton oversaw the creation of a long lineage of Individual-based Models (IbMs) and this paper discusses the five most successful. All of these concern the development of adaptation, covering both evolutionary time and organism lifetime (somatic time). Of the five models discussed here, the first is based on a plant-herbivore model, the other four are based on a substrate-bacteria model, with the option of antibiotics.


Deterioration of Speech Recognition Ability Over a Period of 5 Years in Adults Ages 18 to 70 Years: Results of the Dutch Online Speech-in-Noise Test.
The first aim of the present study was to determine the change in speech recognition in noise over a period of 5 years in participants ages 18 to 70 years at baseline. The second aim was to investigate whether age, gender, educational level, the level of initial speech recognition in noise, and reported chronic conditions were associated with a change in speech recognition in noise. The baseline and 5-year follow-up data of 427 participants with and without hearing impairment participating in the National Longitudinal Study on Hearing (NL-SH) were analyzed. The ability to recognize speech in noise was measured twice with the online National Hearing Test, a digit-triplet speech-in-noise test. Speech-reception-threshold in noise (SRTn) scores were calculated, corresponding to 50% speech intelligibility. Unaided SRTn scores obtained with the same transducer (headphones or loudspeakers) at both test moments were included. Changes in SRTn were calculated as a raw shift (T1 - T0) and an adjusted shift for regression towards the mean. Paired t tests and multivariable linear regression analyses were applied. The mean increase (i.e., deterioration) in SRTn was 0.38-dB signal-to-noise ratio (SNR) over 5 years (p < 0.001). Results of the multivariable regression analyses showed that the age group of 50 to 59 years had a significantly larger deterioration in SRTn compared with the age group of 18 to 39 years (raw shift: beta: 0.64-dB SNR; 95% confidence interval: 0.07-1.22; p = 0.028, adjusted for initial speech recognition level - adjusted shift: beta: 0.82-dB SNR; 95% confidence interval: 0.27-1.34; p = 0.004). Gender, educational level, and the number of chronic conditions were not associated with a change in SRTn over time. No significant differences in increase of SRTn were found between the initial levels of speech recognition (i.e., good, insufficient, or poor) when taking into account the phenomenon regression towards the mean. The study results indicate that hearing deterioration of speech recognition in noise over 5 years can also be detected in adults ages 18 to 70 years. This rather small numeric change might represent a relevant impact on an individual's ability to understand speech in everyday life.


Regioselectivity control in a ruthenium-catalyzed cycloisomerization of diyne-ols.
The ruthenium-catalyzed cycloisomerization of diynes containing one silyl alkyne and one propargyl alcohol yields 2-silyl-[6H]-pyrans instead of the expected unsaturated acylsilanes except when additional conjugation of a aromatic ring is present at the delta-position. Under certain conditions, a facile ruthenium-catalyzed isomerization of the product takes place as well. This regioselectivity of the cyclization can be controlled by the choice of solvent system. DFT calculations confirm the expected greater stability of the silyl-pyrans relative to the acylsilanes.


Recent advances in the development of electrochemical aptasensors for detection of heavy metals in food.
Heavy metal contamination in environment and food has attracted intensive attention from the public since it poses serious threats to ecological system and human health. Traditional detection methods for heavy metals such as atomic absorption spectrometry have a fairly low detection limit, but the methods have many limitations and disadvantages. Therefore, it is of significance to develop a rapid technology for real-time and online detection of heavy metals. The electrochemical aptasensor-based technology is promising in the detection of heavy metals with advantages of high sensitivity, specificity, and accuracy. Although its development is rapid, more researches should be carried out before this technology can be used for on-site detection. In this review, the origin, basic principles and development of electrochemical aptasensors are introduced. The applications of nanomaterials and electrochemical aptasensors for the detection of heavy metals (mainly mercury, lead, cadmium, and arsenic) are summarized. The research and application tendency of electrochemical aptasensors for detection of heavy metals are prospected.


Epidemiology of IBS.
Irritable bowel syndrome (IBS) is a common functional gastrointestinal (GI) disorder. Because not everyone needs to seek care, population-based studies are needed to truly understand the epidemiology of IBS. About 10% of the population has IBS at any one time and about 200 people per 100,000 will receive an initial diagnosis of IBS over the course of a year. IBS patients are more frequently younger in age, and a female predominance has been observed in Western countries and tertiary care settings. IBS patients commonly report overlapping upper GI, as well as a variety of non-GI, complaints.


A New Class of Zn1 -x Fex -Oxyselenide and Zn1- x Fex -LDH Nanostructured Material with Remarkable Bifunctional Oxygen and Hydrogen Evolution Electrocatalytic Activities for Overall Water Splitting.
The scalable and cost-effective H2 fuel production via electrolysis demands an efficient earth-abundant oxygen and hydrogen evolution reaction (OER, and HER, respectively) catalysts. In this work, for the first time, the synthesis of a sheet-like Zn1- x Fex -oxyselenide and Zn1- x Fex -LDH on Ni-foam is reported. The hydrothermally synthesized Zn1- x Fex -LDH/Ni-foam is successfully converted into Zn1- x Fex -oxyselenide/Ni-foam through an ethylene glycol-assisted solvothermal method. The anionic regulation of electrocatalysts modulates the electronic properties, and thereby augments the electrocatalytic activities. The as-prepared Zn1- x Fex -LDH/Ni-foam shows very low OER and HER overpotentials of 263 mV at a current density of 20 mA cm-2 and 221 mV at 10 mA cm-2 , respectively. Interestingly, this OER overpotential is decreased to 256 mV after selenization and the HER overpotential of Zn1- x Fex -oxyselenide/Ni-foam is decreased from 238 to 202 mV at 10 mA cm-2 after a stability test. Thus, the Zn1- x Fex -oxyselenide/Ni-foam shows superior bifunctional catalytic activities and excellent durability at a very high current density of 50 mA cm-2 . More importantly, when the Zn1- x Fex -oxyselenide/Ni-foam is used as the anode and cathode in an electrolyzer for overall water splitting, Zn1- x Fex -oxyselenide/Ni-foam(+)ǁZn1- x Fex -oxyselenide/Ni-foam(-) shows an appealing potential of 1.62 V at 10 mA cm-2 . The anionic doping/substitution methodology is new and serves as an effective strategy to develop highly efficient bifunctional electrocatalysts.


An optimized method to process mouse CNS to simultaneously analyze neural cells and leukocytes by flow cytometry.
Flow cytometry is an efficient and powerful technique to characterize and quantify numerous cells. However, the strengths of this technique have not been widely harnessed in neurosciences due to the critical step of CNS tissue preparation into a single cell suspension. Previous reports assessed either neural cells or infiltrating leukocytes but simultaneous detection has not been extensively implemented. We optimized CNS tissue preparation for flow cytometry analysis. We subjected CNS tissue from individual adult mice to different digestion protocols and Percoll™ methods. We quantified and characterized by flow cytometry neural cells (neurons, oligodendrocytes, microglia) and leukocytes (macrophages, T lymphocytes). The one step Percoll™ method significantly increased cell yield compared to the gradient Percoll™ method. The collagenase D+DNase I digestion led to the maximal cell number recovery while preserving cell marker (O4, NeuN, CD45, CD11b, CD3, CD4, CD8) integrity compared to papain, trypsin digestion, and no digestion. The combination of collagenase D+DNase I digestion and one step Percoll™ method was optimal for the recovery and analysis of cells from the CNS of naïve and experimental autoimmune encephalomyelitis (multiple sclerosis model) mice. Although flow cytometry does not reveal CNS localization, this technique allows concurrent quantification of multiple parameters. In contrast to other protocols, our novel method simultaneously analyzes neural and immune cells in individual mice in healthy and pathological conditions. We strongly believe that the field of neurosciences will benefit from an optimal use of flow cytometry to elucidate physiological and pathological processes.