Premature awakening and underuse of neuromuscular monitoring in a registry of patients with butyrylcholinesterase deficiency.
Patients with butyrylcholinesterase (BChE) deficiency can experience prolonged paralysis after receiving suxamethonium or mivacurium. We hypothesized that patients suspected of BChE deficiency had a higher risk of being awakened while paralysed and having respiratory complications if neuromuscular monitoring was not applied before awakening. We retrospectively included patients referred to the Danish Cholinesterase Research Unit between 2004 and 2012 on suspicion of BChE deficiency. We collected data on genotype, BChE activity, neuromuscular blocking agents administered, neuromuscular monitoring, and postoperative respiratory complications, defined as arterial oxygen desaturation <90%, assisted ventilation, reintubation of the trachea, and pulmonary aspiration. Patients were classified as prematurely awakened if anaesthesia had been terminated while the patient was still paralysed. We included 123 patients. Neuromuscular monitoring was applied before awakening in 48 (39%) patients. A nerve stimulator was never used or only after attempted awakening in the remaining 75 (61%) patients. Premature awakening occurred in 75 (100%) and 14 (29%) of the unmonitored and monitored patients, respectively (P<0.001, Fisher's exact test). In 11 of the monitored patients, the results of neuromuscular monitoring were interpreted as equipment failure or were disregarded. Respiratory complications occurred in 19 (25%) and five (10%) of the unmonitored and monitored patients, respectively (P=0.06). Patients with BChE deficiency are at higher risk of being awakened while paralysed if neuromuscular monitoring is not applied or used; neuromuscular monitoring is recommended whenever a neuromuscular blocking agent is administered.


Blood-brain barrier permeability differentiates Sadowski mouse lines of high and low stress-induced analgesia: electron microscopy analysis.
The blood-brain barrier (BBB) forms a filtering system between peripheral circulating blood and the central nervous system. Pathological leakage of the BBB is probably responsible for various dysfunctions and diseases. Over twenty years ago, Sadowski et al. separated two lines of mouse, one with high sensitivity (HA) and the other with low sensitivity (LA) to stress-induced analgesia (SIA). We propose that leakage of the BBB is responsible for the difference in SIA of the "Sadowski mouse" model. The presented BBB electron microscopy structural analysis of both lines provided evidence for this hypothesis. Up to now, a good natural animal model of differences of BBB permeability is not known. The "Sadowski mouse" may fulfil this deficiency.


[Why to treat a total chronic coronary occlusion?]
Despite an incidence of about 15% of the patients undergoing coronary angiography, total chronic occlusions (CTO) are rarely revascularized by percutaneous angioplasty (PCI). Nevertheless, current evidence suggest that successful CTO-PCI improve symptoms, quality of live and long-term survival. During the last years, improvement of specific techniques for these complexes procedures and increasing experience of operators allow actually to obtain success and complications rates almost equivalent to non-CTO lesions angioplasty. This review focus on the clinical benefits of CTO revascularization and on appropriate patient selection.


Interface Engineering of Co-LDH@MOF Heterojunction in Highly Stable and Efficient Oxygen Evolution Reaction.
The electrochemical splitting of water into hydrogen and oxygen is considered one of the most promising approaches to generate clean and sustainable energy. However, the low efficiency of the oxygen evolution reaction (OER) acts as a bottleneck in the water splitting process. Herein, interface engineering heterojunctions between ZIF-67 and layered double hydroxide (LDH) are designed to enhance the catalytic activity of the OER and the stability of Co-LDH. The interface is built by the oxygen (O) of Co-LDH and nitrogen (N) of the 2-methylimidazole ligand in ZIF-67, which modulates the local electronic structure of the catalytic active site. Density functional theory calculations demonstrate that the interfacial interaction can enhance the strength of the Co-Oout bond in Co-LDH, which makes it easier to break the H-Oout bond and results in a lower free energy change in the potential-determining step at the heterointerface in the OER process. Therefore, the Co-LDH@ZIF-67 exhibits superior OER activity with a low overpotential of 187 mV at a current density of 10 mA cm-2 and long-term electrochemical stability for more than 50 h. This finding provides a design direction for improving the catalytic activity of OER.


Modeling the environmental fate of cadmium in a large wastewater irrigation area.
The fate of cadmium in soils is governed by spatially heterogeneous processes that proceed from decades to centuries. This study aimed at modeling the fate of Cd within the wastewater irrigation area (WIA) of Braunschweig (Germany). The sandy soils (mainly Dystric Cambisol or Typic Haplumbrept) at this site (28 km2) have received considerable loads of heavy metals by irrigation of municipal wastewater for up to 40 yr. The soils of the WIA are in agricultural use. The main crops are sugar beet (Beta vulgaris L.), potato (Solanum tuberosum L.), and wheat (Triticum aestivum L.). As a result of asparagus (Asparagus officinalis L.) cropping, about 15% of the soils have been converted to Rigosols. In 1996, we measured the vertical distribution (0 to 1.2 m) of soil pH, organic carbon content, and the EDTA-extractable content and the solution phase concentration of Cd at 153 sites. At sites not used for asparagus cultivation, Cd has migrated on average to a depth of about 0.5 m. Due to deep plowing, which accelerates migration, Cd has been displaced on average to about 0.7 m at the Rigosol sites. To model the fate of Cd at the scale of the WIA, we used different parallel soil column approaches. In each column the local model SEFAH was used to simulate both displacement and plant uptake of Cd. The model was fed with measured or randomly generated soil data. The results of retrospective simulations from 1957 to 1996 agreed well with observed Cd profiles. The better the spatial variability of sorption was described, the better the performance. Our simulation results show that Cd pollution of soil at first affects the soil-plant pathway. The breakthrough of Cd to the groundwater is dampened and is delayed for many decades.


Proteome Changes in Stem Tissues of Sunflower Lines Inoculated with Culture Filtrate of Sclerotinia sclerotiorum.
Sclerotinia sclerotiorum (Lib.) de Bary cause a deleterious disease on sunflower plants. Oxalic acid is the main pathogenicity factor of S. sclerotiorum. Two dimensional gel electrophoresis and mass spectrometry have been used in several studies to investigate molecular changes that occur in the plants in response to S. sclerotiorum infection. Comparing responses of resistant and susceptible lines upon pathogen infection provided novel information regarding defense mechanisms against this necrotrophic pathogen. The present study reports proteome changes of partially resistant and susceptible sunflower lines under pathogen's culture filtrate treatment, resulting in the characterization of up- and down- regulated proteins. Sunflower partially resistant and susceptible lines with two true leaves were exposed to fungus culture filtrate. The stems of treated and untreated plants were sampled at 24, 48 and 72 hours after treatment for two-dimensional electrophoresis. Twenty spots showed more than 1.5-fold change in abundance were subjected to MALDI/TOF-TOF MS for further analysis. The identified proteins were categorized into several classes including carbohydrate and energy metabolism (25%), cellular metabolic process (15%), stress response (15%), plant cell wall biogenesis (10%), photosynthesis (10%), protein metabolism (10%), unknown function (10%) and redox homeostasis (5%). Our proteomic investigation demonstrates an increase in the expression of proteins only in partially resistant line, such as proteins involved in carbohydrate metabolism and plant defense responses (malate dehydrogenase and peroxidase), metabolic process (adenosine kinase), regulating cell redox homeostasis (disulfide isomerase) and lignin biosynthetic process (laccase). Moreover, the expression of pyrroline-5-carboxylate reductase, involved in proline biosynthesis, was significantly changed in both sunflower lines in response to pathogen culture filtrate. Proteins which were only up-regulated in the partially resistant lines might have a significant role in mediating the defense against Sclerotinia and could be considered for enhancing resistance against this devastating pathogen.


Fluoroscopic guided fogarty embolectomy for an angio-seal embolism in the popliteal artery.
The Angio-Seal is a widely used arterial closure device that helps achieve faster hemostasis and provide early ambulation to patients. However, it can cause various complications in clinical practice. We present the uncommon complication of popliteal artery occlusion following Angio-Seal deployment, and describe an effective interventional approach to its treatment. Because fluoroscopy-guided Fogarty embolectomy has the advantages of complete removal of the embolus without fragmentation, and clear visualization of the exact location of the embolus during the procedure, it is a suitable method for treating this complication.


Metabolism and cellular functions of IP6: a review.
Inositol hexaphosphate (IP6) has a demonstrably effective anti-cancer action against a variety of experimental tumors. However, the mechanisms of its actions are yet to be completely discerned. Studies in my laboratory have shown that IP6 is rather rapidly absorbed by rats in vivo. Ion exchange chromatography demonstrates the presence of inositol and IP1-6 in gastric epithelial cells as early as within 1 h of intragastric 3H-IP6 administration. The metabolized IP6, in the form of inositol and IP1 is transported via plasma and reaches distant organs as well as tumors. In rats, the urinary metabolites of IP6 are inositol and IP1. However, in humans 1-3% of total administered IP6 is excreted in the urine as IP6; the level shows a normal oscillation between 0.5-6 mg/L [F. Grases et al]. Investigations of the uptake and metabolism by a variety of cancer cell lines in vitro also demonstrate an instantaneous absorption of IP6. The rate and pattern at which IP6 is metabolized by cancer cells varies depending on the cell type. Intracellular inositols accumulated mostly (80-97%) in the cytosol as inositol and IP1-6. IP6 treatment of all the cell lines tested so far demonstrates that it is cytostatic and not cytotoxic. Along with inhibition of cell proliferation, there is enhanced differentiation of malignant cells to a more mature phenotype, often resulting in reversion to normal. Studies of the expression of tumor suppressor gene demonstrate up-regulation of wild type p53 and down-regulation of the mutant form. Since p53-mediated cell cycle arrest may be the direct result of induction of WAF-1 gene (p21WAF-1/CIP1), our studies demonstrate that IP6 up-regulates the expression of p21WAF-1/CIP1 in a dose-dependent manner. These data strongly point towards the involvement of signal transduction pathways, cell cycle regulatory genes, differentiation genes, oncogenes and perhaps, tumor suppressor genes in bringing about the observed anti-neoplastic action of IP6.


E3 Ligase FBXW2 Is a New Therapeutic Target in Obesity and Atherosclerosis.
Chronic low-grade inflammation orchestrated by macrophages plays a critical role in metabolic chronic diseases, like obesity and atherosclerosis. However, the underlying mechanism remains to be elucidated. Here, the E3 ubiquitin ligase F-box/WD Repeat-Containing Protein 2 (FBXW2), the substrate-binding subunit of E3 ubiquitin ligase SCF (a complex of FBXW2, SKP1, and cullin-1), as an inflammatory mediator in macrophages, is identified. Myeloid-specific FBXW2 gene deficiency improves both obesity-associated with insulin resistance and atherosclerosis in murine models. The beneficial effects by FBXW2 knockout are accompanied by decreased proinflammatory responses and macrophage infiltration in the microenvironment. Mechanistically, it is identified that KH-type splicing regulatory protein (KSRP) is a new bona fide ubiquitin substrate of SCFFBXW2. Inhibition of KSRP prevents FBXW2-deficient macrophages from exerting a protective effect on inflammatory reactions, insulin resistance and plaque formation. Furthermore, it is demonstrated that the C-terminus (P3) of FBXW2 competitively ablates the function of FBXW2 in KSRP degradation and serves as an effective inhibitor of obesity and atherogenesis progression. Thus, the data strongly suggest that SCFFBXW2 is an important mediator in the context of metabolic diseases. The development of FBXW2 (P3)-mimicking inhibitors and small-molecular drugs specifically abrogating KSRP ubiquitination-dependent inflammatory responses are viable approaches for obesity and atherosclerosis treatment.


Human Txk: genomic organization, structure and contiguous physical linkage with the Tec gene.
Txk is a Tec-family tyrosine kinase expressed in mouse and human T lymphocytes. Among the Tec kinases, Txk is unique in that its amino terminal region does not include a pleckstrin homology domain or other known extended functional region. Txk is encoded at human chromosome 4p12 and at a recognized region of conserved synteny on mouse chromosome 5. The genomic organization of Txk consists of 15 exons with strong exon-intron organizational homology to Btk, the only other Tec-family kinase for which the genomic structure is fully known. The human Tec gene also maps to 4p12 and, based on limited studies reported here, possesses organizational homology with Btk and Txk. We have sequenced a continuous region of DNA that contains 3' Tec and 5' Txk exons separated by only a approximately 1.5 kb intergenic region containing the putative promoter region of Txk. The close physical linkage of these Tec-family tyrosine kinases, which are expressed in different hematopoetic cell lineages, suggests their potential for coordinate cis-regulation.


Evaluation of surgery for the tethered cord syndrome using a new grading system.
A new grading system is presented to assess the degree of untethering achieved at surgery for the 'tethered cord syndrome' based on intraoperative observation at the end of the procedure. Various pathophysiological mechanisms responsible for the 'tethered cord syndrome', as well as possible factors causing retethering were considered in developing this grading system. In Grade I the cord is considered to be fully untethered and the factors potentially responsible for retethering are eliminated, in Grade II partial untethering is performed and in Grade III untethering is unsuccessful. This grading system was used to assess the results of 22 consecutive operations performed to release a tethered cord between June 1991 and February 1995. The tethering factors encountered at surgery were: spinal lipoma in 14, diastematomyelia in five, a tight filum terminale in 10 and intradural adhesions in three instances. The grade of untethering was correlated with the type of pathology encountered, postoperative results, and whether previous surgery was performed or not. Previous surgery was found not to affect the rate of subsequent successful untethering.


CircAKT3 promotes cell proliferation, survival and glutamine metabolism of gastric cancer by activating SLC1A5 expression via targeting miR-515-5p.
Gastric cancer (GC) is a common disorder in the population. Numerous studies have reported that the pathogenesis of GC is implicated in the dysregulation of circular RNAs (circRNAs). The aim of this study was to investigate the role and functional mechanism of circ_0000199 (circAKT3) in GC. The expression of circAKT3, miR-515-5p and solute carrier family 1 member 5 (SLC1A5) mRNA was measured by quantitative real-time PCR (qPCR). Cell proliferation was assessed by cell counting kit-8 (CCK-8) assay, colony formation assay and 5-ethynyl-2'-deoxyuridine (EdU) assay. Cell apoptosis was determined by flow cytometry assay and caspase 3/7 activity. The protein levels of glutaminase (GLS), proliferating cell nuclear antigen (PCNA) and cleaved-caspase3 were detected by western blot. The binding relationship between miR-515-5p and circAKT3 or SLC1A5 was verified by dual-luciferase reporter assay or RIP assay. The role of circAKT3 in vivo was investigated by establishing animal models. The abundance of Ki-67 and PCNA was detected by IHC assay. The expression of circAKT3 in GC tissues and cells was enhanced. The knockdown of circAKT3 inhibited GC cell proliferation, survival and glutamine metabolism, as well as tumor growth in animal models. MiR-515-5p was a target of circAKT3, and miR-515-5p suppressed the expression of SLC1A5 by binding to SLC1A5 3'UTR. CircAKT3 relieved the inhibition of miR-515-5p on SLC1A5 expression by targeting miR-515-5p. The effects of circAKT3 knockdown were reversed by miR-515-5p depletion, and the effects of miR-515-5p restoration were abolished by SLC1A5 overexpression. CircAKT3 promotes the malignant development of GC by activating SLC1A5 expression via targeting miR-515-5p.


Linear position-sensitive x-ray detector incorporating a self-scanning photodiode array.
A linear position-sensitive x-ray detector for x-ray spectroscopy and diffraction applications has been tested which can provide excellent spatial resolution, wide dynamic range and good sensitivity. The heart of the system is a self-scanning, photosensitive silicon diode array. It is interfaced via fiber optics to a thin layer of ZnS which fluoresces visible light upon absorption of x-radiation. The conversion to visible light and optical coupling provide several-fold gain in the efficiency of detection as compared to the direct detection of x-ray by the diode array. Equally important is that the array is protected from irreversible damage by high energy radiation, a limitation which previously hindered this application of silicon diode technology.


Approach to Neurological Channelopathies and Neurometabolic Disorders in Newborns.
Ion channel disorders (channelopathies) can affect any organ system in newborns before 2 months of life, including the skeletal muscle and central nervous system. Channelopathies in newborns can manifest as seizure disorders, which is a critical issue as early onset seizures can mimic the presentation of neurometabolic disorders. Seizures in channelopathies can either be focal or generalized, and range in severity from benign to epileptic encephalopathies that may lead to developmental regression and eventually premature death. The presenting symptoms of channelopathies are challenging for clinicians to decipher, such that an extensive diagnostic survey through a precise step-by-step process is vital. Early diagnosis of a newborn's disease, either as a channelopathy or neurometabolic disorder, is important for the long-term neurodevelopment of the child.


Characterization of an Arabidopsis thaliana gene that defines a new class of putative plant receptor kinases with an extracellular lectin-like domain.
We have characterized an Arabidopsis receptor-like serine/threonine kinase gene, Ath.lecRK1 (Arabidopsis thaliana lectin-receptor kinase), defining a new and putatively important class of plant receptor kinases. Structural features of the predicted polypeptide include an amino-terminal membrane-targeting signal sequence, a legume lectin-like extracellular domain, a single membrane-spanning domain, and a characteristic serine/threonine protein kinase domain. A recombinant protein containing the kinase domain can be autophosphorylated on a serine residue. Ath.lecRK1 is a member of a gene family of at least two closely related genes. Northern blot analysis indicates that the Ath.lecRK1 gene is weakly expressed in a variety of organs and is regulated in Arabidopsis cell suspension cultures according to the growth phase of cells. The role this new class of plant receptor kinase could play is discussed with regard to the transduction of oligosaccharide and plant hormone signals.


Precocious transitions and long-term heroin use outcomes: A longitudinal study of gang-affiliated Mexican-American males.
A longitudinal study (15years) investigates heroin use patterns following precocious transition experiences for gang-affiliated Mexican-American males (n=119) in San Antonio, Texas. Five precocious transitions are examined: cohabitation, early nest leaving, school dropout, teenage parenthood, and unemployment (while not in school). Half of these men used heroin over the follow-up period for an average of under 4years. Findings from a zero-inflated Poisson model indicate that while these transitions do not have a significant effect on initiation of heroin use, they do have an important influence on individual's drug trajectories once they have initiated. Early-nest leaving and teenage parenthood are protective factors for continued heroin use while dropping out of high school and cohabiting during this same period are risk factors. Findings are discussed within the context of these disadvantaged and marginalized communities.


Fluid flow through nanometer-scale channels.
We describe studies of the pressure driven flow of several classical fluids through lithographically produced channels in which one dimension, the channel height h, is in the micron or nanometer size range. The measured flow rates are compared with theoretical predictions assuming no-slip boundary conditions at the walls of the channel. The results for water agree well with this prediction for h as small as 40 nm (our smallest channels). However, for hexane, decane, hexadecane, and silicone oil we find deviations from this theory when h is reduced below about 100 nm. The observed flow rates for small h are larger than theoretical expectations, implying significant slip at the walls, and values of the slip length are estimated. The results are compared with previous experimental and theoretical work.


Expression of human lysozyme in an insoluble form in yeast.
A high level of expression in yeast of a chemically synthesized human lysozyme (hL) gene was achieved by introducing an A-rich DNA fragment just upstream from the ATG start codon. The synthesized recombinant human lysozyme (r-hL) was insoluble and biologically inactive. It was solubilized with 7 M urea (pH 9) from yeast cells and its lytic activity was efficiently regenerated by oxidative renaturation. This renaturation experiment and Western blotting analysis under reducing and non-reducing conditions indicate that the insoluble form might be caused by the formation of incorrect intra- or intermolecular disulfide bonds. The N-terminal amino acid sequence of the purified r-hL was identical with that of authentic hL.


Epigenetic inactivation of the Sotos overgrowth syndrome gene histone methyltransferase NSD1 in human neuroblastoma and glioma.
Sotos syndrome is an autosomal dominant condition characterized by overgrowth resulting in tall stature and macrocephaly, together with an increased risk of tumorigenesis. The disease is caused by loss-of-function mutations and deletions of the nuclear receptor SET domain containing protein-1 (NSD1) gene, which encodes a histone methyltransferase involved in chromatin regulation. However, despite its causal role in Sotos syndrome and the typical accelerated growth of these patients, little is known about the putative contribution of NSD1 to human sporadic malignancies. Here, we report that NSD1 function is abrogated in human neuroblastoma and glioma cells by transcriptional silencing associated with CpG island-promoter hypermethylation. We also demonstrate that the epigenetic inactivation of NSD1 in transformed cells leads to the specifically diminished methylation of the histone lysine residues H4-K20 and H3-K36. The described phenotype is also observed in Sotos syndrome patients with NSD1 genetic disruption. Expression microarray data from NSD1-depleted cells, followed by ChIP analysis, revealed that the oncogene MEIS1 is one of the main NSD1 targets in neuroblastoma. Furthermore, we show that the restoration of NSD1 expression induces tumor suppressor-like features, such as reduced colony formation density and inhibition of cellular growth. Screening a large collection of different tumor types revealed that NSD1 CpG island hypermethylation was a common event in neuroblastomas and gliomas. Most importantly, NSD1 hypermethylation was a predictor of poor outcome in high-risk neuroblastoma. These findings highlight the importance of NSD1 epigenetic inactivation in neuroblastoma and glioma that leads to a disrupted histone methylation landscape and might have a translational value as a prognostic marker.


ASTM F1717 standard for the preclinical evaluation of posterior spinal fixators: can we improve it?
Preclinical evaluation of spinal implants is a necessary step to ensure their reliability and safety before implantation. The American Society for Testing and Materials reapproved F1717 standard for the assessment of mechanical properties of posterior spinal fixators, which simulates a vertebrectomy model and recommends mimicking vertebral bodies using polyethylene blocks. This set-up should represent the clinical use, but available data in the literature are few. Anatomical parameters depending on the spinal level were compared to published data or measurements on biplanar stereoradiography on 13 patients. Other mechanical variables, describing implant design were considered, and all parameters were investigated using a numerical parametric finite element model. Stress values were calculated by considering either the combination of the average values for each parameter or their worst-case combination depending on the spinal level. The standard set-up represents quite well the anatomy of an instrumented average thoracolumbar segment. The stress on the pedicular screw is significantly influenced by the lever arm of the applied load, the unsupported screw length, the position of the centre of rotation of the functional spine unit and the pedicular inclination with respect to the sagittal plane. The worst-case combination of parameters demonstrates that devices implanted below T5 could potentially undergo higher stresses than those described in the standard suggestions (maximum increase of 22.2% at L1). We propose to revise F1717 in order to describe the anatomical worst case condition we found at L1 level: this will guarantee higher safety of the implant for a wider population of patients.


Role of spinning top urethra in dysfunctional voiding.
The role of spinning top urethra (STU) in children with dysfunctional voiding was evaluated retrospectively. From 1995 to 2002, the records of 154 children with dysfunctional voiding were reviewed retrospectively. Of the children 110 (71%) were girls and 44 (29%) were boys (mean age 8 years, range 4-14). All children were neurologically normal and no exhibited physical signs of occult spinal dysraphism. Patients were divided into two groups according to their width of proximal urethra: group I had STU and the group II had normal urethral width. The groups were compared with each other for gender, voiding symptoms, urinary tract infection (UTI), vesicoureteral reflux (VUR) and urodynamic observations. There were 84 children (mean age 8.3 +/- 2.2 years, range 4-14) in group I and 70 (mean age 8.0 +/- 2.1 years, range 4-14) in group II; no significant age difference was found between the two groups (p = 0.4674). Group I consisted of 66 (71%) girls and 18 (29%) boys and group II 44 (63%) girls and 26 (37%) boys. STU was observed more in girls than boys in group I (p = 0.0316). UTI was observed in 57 patients (68%) in group I and 34 (49%) in group II (p = 0.0154). Mean duration of symptoms was 42 +/- 24 months (range 6-118) and 39 +/- 23 (range 3-120) months in groups I and II, respectively (p = 0.6302). Postvoid residual urine (PVR) more than 10% of expected bladder capacity was detected in 15 patients (18%) in group I and seven (10%) in group II. No association was found between the meaningful PVR and STU (p = 0.1653). The presence of detrusor overactivity during filling was observed in 54 patients (64%) in group I and 42 (60%) in group II (p = 0.4676). Diminished bladder compliance (< 10 ml/cmH(2)O) was detected in 34 patients (40%) in group I and 17 (24%) in group II (p = 0.0335). The mean voiding pressure was measured as 56 +/- 29 cmH(2)O in group I, which was significantly higher than in group II (49 +/- 25 cmH(2)O) (p = 0.0373). The mean flow rate during the emptying phase of urodynamics was 16 +/- 8 and 15 +/- 6 ml/s in groups I and II, respectively (not significant, p = 0.2686). VUR was detected in 16 patients (19%) in group I and two (3%) in group II (p = 0.0018). STU was related to recurrent UTIs, VUR, poor bladder compliance and more serious functional urinary obstruction. Furthermore, STU may be a consequence of a neurogenic maturation defect in detrusor-sphincter coordination resembling that of urofacial syndrome, because development of this situation was found to be independent of the duration of symptoms.


Associations between questionnaires on lifestyle and atherosclerotic cardiovascular disease in a Japanese general population: A cross-sectional study.
We aimed to investigate the association between questionnaires related to lifestyle habits and atherosclerotic cardiovascular diseases (ASCVD). Cross-sectional observational study. Community-based medical checkups, called specific health checkups started in Japan since 2008. This checkup includes standard medical examinations as well as a specific questionnaire related to lifestyle habits. Overall, 47,842 subjects (males = 16,913, 35.4%) aged ≥40 years who underwent a Japanese specific health checkup in 2014 in Kanazawa city were included. Association between 12 lifestyle habits-related questionnaires and the presence of ASCVD, including coronary artery disease and stroke. The questionnaire included the following 12 questions on lifestyle habits: 1) weight gain (>10 kg/20 years), 2) exercise (>30 min, twice a week, >1 year), 3) daily walking or equivalent (>1 h), 4) walking faster (than others in the same generation), 5) body weight changes (>3 kg/year), 6) eating faster (than others in the same generation), 7) eating within 2 h before going to bed (more than three times a week), 8) having a snack after dinner (more than three times a week), 9) skipping breakfast (more than three times a week), 10) daily drinking (alcohol), 11) heavy drinking (more than 60 g ethanol/day), and 12) good sleeping. Multivariable logistic regression analyses revealed that walking faster (odds ratio [OR] = 0.74, 95% confidence interval [CI] = 0.69-0.79, p < 0.0003), body weight changes (>3 kg/year, OR = 1.26, 95% CI = 1.16-1.37, p < 0.0003), eating faster (OR = 1.09, 95% CI = 1.03-1.15, p = 0.003), daily drinking (OR = 0.83, 95% CI = 0.76-0.89, p < 0.0003), and good sleeping (OR = 0.86, 95% CI = 0.79-0.93, p < 0.0003) were independently associated with ASCVD. Subjects with a high lifestyle habits risk score (number of bad habits: 7-12) had significantly higher odds for ASCVD than those with a low risk score (number of bad habits: 0-3, OR = 1.78, 95%CI = 1.62-1.95, p < 0.0003). Simple questionnaires related to lifestyle habits were associated with self-reported ASCVD.


Repeated measurements of aperture for individual stomates.
Measurements of stomatal aperture in epidermal peels are used in a variety of physiological studies, but variability between stomates often hinders experimentation. We mount epidermal peels of Vicia faba over a microscopic grid that enables us to map the positions of individual stomates and thus measure the same individual stomates repeatedly, using a simple digitizing system. Repeated measurements of the same population of 15 stomates show much lower variability than measurements of different populations either on the same peel or on different peels.


PGC-1α and FOXO1 mRNA levels and fiber characteristics of the soleus and plantaris muscles in rats after hindlimb unloading.
Fifteen-week-old rats were subjected to unloading induced by hindlimb suspension for 3 weeks. The peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and forkhead box-containing protein O1 (FOXO1) mRNA levels and fiber profiles of the soleus and plantaris muscles in rats subjected to unloading (unloaded group) were determined and compared with those of age-matched control rats (control group). The body weight and both the soleus and plantaris muscle weights were lower in the unloaded group than in the control group. The PGC-1α mRNA was downregulated in the soleus, but not in the plantaris muscle of the unloaded group. The FOXO1 mRNA was upregulated in both the soleus and plantaris muscles of the unloaded group. The oxidative enzyme activity was reduced in the soleus, but not in the plantaris muscle of the unloaded group. The percentage of type I fibers was decreased and the percentages of type IIA and IIC fibers were increased in the soleus muscle of the unloaded group, whereas there was no change in fiber type distribution in the plantaris muscle of the unloaded group. Atrophy of all types of fibers was observed in both the soleus and plantaris muscles of the unloaded group. We conclude that decreased oxidative capacity and fiber atrophy in unloaded skeletal muscles are associated with decreased PGC-1α and increased FOXO1 mRNA levels.


Metabolic requirements for macrophage presentation of Listeria monocytogenes to immune CD8 cells.
Though ingested Ag are readily degraded into peptides within endocytic vesicles, APC usually cannot present these fragments to CD8 cells. Despite this generalization, some exceptions have been noted. For example, murine macrophage targets readily process heat-killed Listeria monocytogenes (HKLM) into a form recognizable by immune CD8 CTL. Using an assay of Listeria-specific, CD8-mediated cytotoxicity to quantitate Ag presentation by C57Bl/6 macrophage targets, we have examined some of the cellular requirements for this form of Ag processing. To assess whether the physical form of the Ag is an important determinant of processing, we compared the ability of macrophages to present intact HKLM, fractionated L. monocytogenes (LM) membranes, and octyl-beta-d-thioglucopyranoside-solubilized extracts of LM membranes. Macrophages presented each Ag form in a similar manner indicating that processing is not critically dependent on the presence of intact bacteria or even on the introduction of Ag in a particulate form. To gain insight into the metabolic requirements for Ag processing, we examined the effects of several inhibitors. As might be expected, listerial Ag presentation was blocked by brefeldin, a known inhibitor of the endogenous pathway of Ag processing. LM Ag presentation, however, was also blocked by inhibitors of endosomal acidification (chloroquine, ammonium chloride, and monensin) and by the acid protease inhibitor pepstatin A, suggesting that endocytic processing may play an essential role in CD8 recognition of this Ag. To formally establish that this pattern of exogenous Ag processing requires the presence of a class I MHC product, we demonstrated that beta-2 microglobulin-deficient macrophages, which lack class I MHC product expression, cannot present HKLM to CD8 cells. However, we could not block Ag presentation by incubating macrophages with monoclonal anti-H-2K or H-2D antibodies, suggesting that LM Ag presentation may be mediated by some other class I MHC product. Additional characterization of this pathway of Ag presentation is warranted in view of its possible role in initiating CD8-mediated immunity against microbial Ag.


Broadly Applicable Hydrogel Fabrication Procedures Guided by YAP/TAZ-Activity Reveal Stiffness, Adhesiveness, and Nuclear Projected Area as Checkpoints for Mechanosensing.
Mechanical signals are pivotal ingredients in how cells perceive and respond to their microenvironments, and to synthetic biomaterials that mimic them. In spite of increasing interest in mechanobiology, probing the effects of physical cues on cell behavior remains challenging for a cell biology laboratory without experience in fabrication of biocompatible materials. Hydrogels are ideal biomaterials recapitulating the physical cues that natural extracellular matrices (ECM) deliver to cells. Here, protocols are streamlined for the synthesis and functionalization of cell adhesive polyacrylamide-based (PAA-OH) and fully-defined polyethyleneglycol-based (PEG-RGD) hydrogels tuned at various rigidities for mechanobiology experiments, from 0.3 to >10 kPa. The mechanosignaling properties of these hydrogels are investigated in distinct cell types by monitoring the activation state of YAP/TAZ. By independently modulating substrate stiffness and adhesiveness, it is found that although ECM stiffness represents an overarching mechanical signal, the density of adhesive sites does impact on cellular mechanosignaling at least at intermediate rigidity values, corresponding to normal and pathological states of living tissues. Using these tools, it is found that YAP/TAZ nuclear accumulation occurs when the projected area of the nucleus surpasses a critical threshold of approximatively 150 µm2 . This work suggests the existence of distinct checkpoints for cellular mechanosensing.


[Gut microbiota and its metabolite trimethylamine-N-oxide (TMAO): a novel regulator in coronary artery disease].
Coronary artery disease (CAD) is a chronic disease but causes the highest mortality and morbidity among the cardiovascular diseases worldwide. Correlations between CAD and gut microbiota have been observed. This suggests that the gut microbiota could become a vital diagnostic marker of CAD, and restoring the gut habitat may become a promising strategy for CAD therapy. The elevated level of trimethylamine-N-oxide (TMAO), a gut microbiota-derived metabolite, was found to be associated with the increased risk of cardiovascular disease and the all-cause mortality. Preclinical studies have shown that it has pro-arteriosclerosis properties. It is likely that regulating the production of TMAO by gut microbiota may become a promising strategy for anti-atherosclerosis therapy. This review summarizes the clinical and preclinical researches on the intervention of CAD by regulating the gut microbiota and the microbiota-derived metabolite TMAO, with the aim to provide new target for the therapy of CAD.


The role of the dorsoanterior striatum in implicit motivation: the case of the need for power.
Implicit motives like the need for power (nPower) scale affective responses to need-specific rewards or punishments and thereby influence activity in motivational-brain structures. In this paper, we review evidence specifically supporting a role of the striatum in nPower. Individual differences in nPower predict (1) enhanced implicit learning accuracy, but not speed, on serial-response tasks that are reinforced by power-related incentives (e.g., winning or losing a contest; dominant or submissive emotional expressions) in behavioral studies and (2) activation of the anterior caudate in response to dominant emotional expressions in brain imaging research. We interpret these findings on the basis of Hikosaka et al.'s (2002a) model of central mechanisms of motor skill learning. The model assigns a critical role to the dorsoanterior striatum in dopamine-driven learning of spatial stimulus sequences. Based on this model, we suggest that the dorsoanterior striatum is the locus of nPower-dependent reinforcement. However, given the centrality of this structure in a wide range of motivational pursuits, we also propose that activity in the dorsoanterior striatum may not only reflect individual differences in nPower, but also in other implicit motives, like the need for achievement or the need for affiliation, provided that the proper incentives for these motives are present during reinforcement learning. We discuss evidence in support of such a general role of the dorsoanterior striatum in implicit motivation.


Responsible consumer and lifestyle: Sustainability insights.
Environmental changes resulting from human activity and the negative impact of civilisational megatrends are being noticed and criticised increasingly often, and their consequences are becoming extremely severe. If people do not change their habits, changes in our ecosystems will become irreversible and it will be impossible to live in such environment. Thus, the aim of the paper is to review the lifestyles of responsible consumers against the background of the sustainable development paradigm. To engage in the debate as to how a sustainable lifestyle can be operationalized, we conducted a traditional, narrative literature review. Apart from revising the theoretical framework of a sustainable lifestyle, we describe selected lifestyles (such as lifestyle of health and sustainability, wellness, hygge, lagom, slow living, smart living, low-carbon lifestyles) and consumer behaviour patterns (fair trade, values and lifestyle segmentation). Each of these lifestyles relates to a broader or narrower extent to sustainable development, but none of the lifestyles is universal. Conscious and responsible consumer behaviour requires a long-term process and to a large extent depends on individual, political and marketing factors. Finally, we made an evaluation of the research used, pointing out challenges to be implemented, which will contribute to the development, enhancement and prominence of a sustainable lifestyle.


Transcriptome Analysis of Rice Reveals the lncRNA-mRNA Regulatory Network in Response to Rice Black-Streaked Dwarf Virus Infection.
The plant genome can produce long non-coding RNAs (lncRNAs), some of which have been identified as important regulators of gene expression. To better understand the response mechanism of rice plants to Rice black-streaked dwarf virus (RBSDV) infection, we performed a comparative transcriptome analysis between the RBSDV-infected and non-infected rice plants. A total of 1342 mRNAs and 22 lncRNAs were identified to be differentially expressed after RBSDV infection. Most differentially expressed transcripts involved in the plant-pathogen interaction pathway were upregulated after RBSDV infection, indicating the activation of rice defense response by RBSDV. A network of differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) was then constructed. In this network, there are 56 plant-pathogen interaction-related DEmRNAs co-expressing with 20 DElncRNAs, suggesting these DElncRNAs and DEmRNAs may play essential roles in rice innate immunity against RBSDV. Moreover, some of the lncRNA-mRNA regulatory relationships were experimentally verified in rice calli by a quick and effective method established in this study. Three DElncRNAs were selected to be tested, and the results indicated that five mRNAs were found to be regulated by them. Together, we give a whole landscape of rice mRNAs and lncRNAs in response to RBSDV infection, and a feasible method to rapidly verify the lncRNA-mRNA regulatory relationship in rice.


The role of obsessive-compulsive symptoms in the psychopathological profile of children with chronic tic disorder and attention-deficit hyperactivity disorder.
The study examines the role of obsessive-compulsive symptoms (OCS) as a part of the psychopathology of children with chronic tic disorders (CTD) and/or attention-deficit hyperactivity disorder (ADHD). We assessed the psychopathology of four large patient groups without further psychiatric disorders: CTD (n = 112), CTD + ADHD (n = 82), ADHD (n = 129), and controls (n = 144)) by implementing the Child Behavior Checklist (CBCL). We compared the main effects for CTD and ADHD with and without including OCS as covariates. Including OCS led to substantially different main effects for CTD on seven out of eight CBCL subscales. Slightly different main effects for ADHD were determined with respect to ADHD, mainly on the subscale withdrawn. OCS are closely related to CTD-associated psychopathology and - to a lesser extent, but nevertheless of importance in daily clinical practice - on ADHD-related symptoms. This information can be helpful in implementing more precise diagnostics and treatment in daily routine care.


Implicit emotion regulation affects outcome evaluation.
Efficient implicit emotion regulation processes, which run without awareness, are important for human well-being. In this study, to investigate the influence of implicit emotion regulation on psychological and electrophysiological responses to gains and losses, participants were required to select between two Chinese four-character idioms to match the meaning of the third one before they performed a monetary gambling task. According to whether their meanings were related to emotion regulation, the idioms fell into two categories. Event-related potentials and self-rating emotional experiences to outcome feedback were recorded during the task. Priming emotion regulation reduced subjective emotional experience to both gains and losses and the amplitudes of the feedback-related negativity, while the P3 component was not influenced. According to these results, we suggest that the application of implicit emotion regulation effectively modulated the subjective emotional experience and the motivational salience of current outcomes without the cost of cognitive resources. This study implicates the potential significance of implicit emotion regulation in decision-making processes.


Endothelial cell pathway for conduction of hyperpolarization and vasodilation along hamster feed artery.
Acetylcholine (ACh) evokes the conduction of vasodilation along resistance microvessels. However, it is not known which cell layer (endothelium or smooth muscle) serves as the conduction pathway. In isolated, cannulated feed arteries ( approximately 70 microm in diameter at 75 mm Hg; length approximately 4 mm) of the hamster retractor muscle, we tested the hypothesis that endothelial cells provide the pathway for conduction. Microiontophoresis of ACh (500 ms, 500 nA) onto the distal end of a feed artery evoked hyperpolarization (-13+/-2 mV) of both cell layers with vasodilation (15+/-1 microm) along the entire vessel. To selectively damage endothelial cells (confirmed by loss of vasodilation to ACh and labeling of disrupted cells with propidium iodide), an air bubble was perfused through a portion of the vessel lumen, or a 70-kDa fluorescein-conjugated dextran (FCD) was illuminated within a segment (300 microm) of the lumen. After endothelial cell damage, hyperpolarization and vasodilation conducted up to, but not through, the treated segment. To selectively damage smooth muscle cells (confirmed by loss of vasoconstriction to phenylephrine and labeling with propidium iodide), FCD was perifused around the vessel and illuminated. Vasodilation and hyperpolarization conducted past the disrupted smooth muscle cells without attenuation. We conclude that endothelial cells provide the pathway for conducting hyperpolarization and vasodilation along feed arteries in response to ACh.


Complex phenotype associated with 17q21.31 microdeletion.
We report on a patient carrying a 17q21.31 microdeletion and exhibiting many common syndrome features, together with other clinical signs which have rarely or never been described to date. The detected 695-kb 17q21.31 deletion is larger than in most previously reported cases but is still probably the result of recombination between flanking low-copy repeats. Due to the complexity of the patient's clinical condition, together with the presence of 3 previously unreported symptoms, namely chronic anemia, cervical vertebrae arthrosis and vertebrae fusion, this case is an important addition to the existing knowledge about the 17q21.31 microdeletion syndrome.


Wnt6 signaling regulates heart muscle development during organogenesis.
Mesodermal tissue with heart forming potential (cardiogenic mesoderm) is induced during gastrulation. This cardiogenic mesoderm later differentiates into heart muscle tissue (myocardium) and non-muscular heart tissue. Inhibition of Wnt/beta-catenin signaling is known to be required early for induction of cardiogenic mesoderm; however, the identity of the inhibiting Wnt signal itself is still elusive. We have identified Wnt6 in Xenopus as an endogenous Wnt signal, which is expressed in tissues close to and later inside the developing heart. Our loss-of-function experiments show that Wnt6 function is required in the embryo to prevent development of an abnormally large heart muscle. We find, however, that Wnt6 is not required as expected during gastrulation stages, but later during organogenesis stages just before cells of the cardiogenic mesoderm begin to differentiate into heart muscle (myocardium). Our gain-of-function experiments show that Wnt6 and also activated canonical Wnt/beta-catenin signaling are capable of restricting heart muscle development at these relatively late stages of development. This repressive role of Wnt signaling is mediated initially via repression of cardiogenic transcription factors, since reinstatement of GATA function can rescue expression of other cardiogenic transcription factors and downstream cardiomyogenic differentiation genes.


Sir David K Henderson and the origins of British occupational therapy.
Sir David K Henderson made several major contributions in the field of psychiatry, gaining an international reputation but, perhaps lesser known is his role in the introduction of occupational therapy in the United Kingdom. The part Henderson played in establishing occupational therapy as an aspect of his evolving approach to treating mental illness in Scotland is discussed, as is the influence he had in stimulating and supporting the early pioneers of the profession elsewhere in the UK.


Influence of Solvent Representation on Nuclear Shielding Calculations of Protonation States of Small Biological Molecules.
In this study, we assess the influence of solvation on the accuracy and reliability of isotropic nuclear magnetic shielding calculations for amino acids in comparison to experimental data. We focus particularly on the performance of solvation methods for different protonation states, as biological molecules occur almost exclusively in aqueous solution and are subject to protonation with pH. We identify significant shortcomings of current implicit solvent models and present a hybrid solvation approach that improves agreement with experimental data by taking into account the presence of direct interactions between amino acid protonation state and water molecules.


Polydextrose: Physiological Function, and Effects on Health.
Polydextrose (PDX) is a non-digestible oligosaccharide used widely across most sectors of the food industry. It is a randomly linked glucose oligomer containing small amounts of sorbitol and citric acid. The random bonds in PDX prevent mammalian digestive enzymes from readily hydrolyzing the molecule and it has a reported energy value of 1 kcal/g. These properties have led to the acceptance in many countries that PDX provides similar physiological effects as other dietary fibers and has shown prebiotic potential. Dietary intervention with prebiotics has been shown to selectively stimulate the growth and/or activity of one or a limited number of intestinal bacteria associated with several physiological benefits on health. Therefore, the objective of this review was a survey of the literature on the effect of supplementation with PDX in health, and to list the benefits for maintaining health and/or reducing the development of diseases.


Two-day thionamide withdrawal prior to radioiodine uptake sufficiently increases uptake and does not exacerbate hyperthyroidism compared to 7-day withdrawal in Graves' disease.
The appropriate period of antithyroid drug (ATD) discontinuation before radioiodine therapy is the most critical problem in Graves' disease patients under going treatment with ATD. To determine the optimal period that does not alter the outcome of radioiodine therapy or exacerbate hyperthyroidism, we compared serum FT4 levels at radioiodine uptake (RAIU) and therapy outcomes between a 2-day withdrawal group and 7-day withdrawal group. We prospectively recruited 43 patients for the 2-day withdrawal protocol and retrospectively reviewed 49 patients treated with radioiodine following the protocol of 7-day withdrawal. There was no significant difference in RAIU between the 2 groups. The mean serum FT4 level measured on the first day of 24-h RAIU of the 7-day group was significantly higher than that in the 2-day group. There were no significant differences in the outcomes at each point (6 months, 1 year, and 2 years after therapy) between the 2 groups. Our results indicated that withdrawal of ATD for 2 days is superior to 7 days in that 2 days discontinuation did not exacerbate hyperthyroidism. In order to prevent serum thyroid hormone increase after ATD withdrawal and radioiodine therapy, a 2-day ATD withdrawal period before radioiodine therapy may be useful for high-risk patients such as the elderly and patients with cardiac complications. We believe that the 2-day ATD withdrawal method may be useful for patients undergoing treatment with ATD who are to undergo radioiodine therapy.


[Activity of aminopeptidase and inter-alpha-trypsin inhibitor in serum of women in physiological labor].
Aminopeptidase activity was measured towards L-alanine and L-leucine naphtylamides in the blood serum obtained from the non-pregnant women and from women during the stages of the physiological delivery. In the same samples the concentration of inter-alpha-trypsin inhibitor (alpha ITI) was measured. The highest aminopeptidase activity was observed in the stage II, and it was statistically significant comparing to the stage I, whereas the statistically significant increase in the alpha ITI concentration was noticed in stage I in primiparae and in stage I in multiparae.


Do women forget their births? A study of maternity histories in a rural area of Senegal (Niakhar).
5068 maternity histories were recorded among women aged 15-89 years in a rural area of Senegal. The quality of the estimates of fertility, child mortality, and perinatal mortality was analyzed for consistency. There was no evidence of any major underreporting of births, deaths, or still births according to age, even among the oldest women. Estimates were compared with comparable values derived from a longitudinal demographic surveillance system (DSS) in the same area. The age patterns of cumulated fertility and mortality derived from the maternity histories were consistent with those of the DSS. Differences in the levels of fertility and mortality with respect to the longitudinal records could be explained by small differences within the selected villages, by selection biases, and by recent trends in demographic parameters. Values of perinatal mortality were also equivalent to those recorded by the DSS. Women did not seem to forget their births to an extent large enough to produce strong biases, even at older ages. However, an analysis of differences by field workers revealed that some 2% of the births and 4% of the deaths may have been omitted, which gives an idea of the potential accuracy of maternity histories for the estimation of fertility and mortality levels.


Genome sequence of an uncharted halophilic bacterium Robertkochia marina with deciphering its phosphate-solubilizing ability.
The wide use of whole-genome sequencing approach in the modern genomic era has opened a great opportunity to reveal the prospective applications of halophilic bacteria. Robertkochia marina CC-AMO-30DT is one of the halophilic bacteria that was previously taxonomically identified without any inspection on its biotechnological potential from a genomic aspect. In this study, we present the whole-genome sequence of R. marina and demonstrated the ability of this bacterium in solubilizing phosphate by producing phosphatase. The genome of R. marina has 3.57 Mbp and contains 3107 predicted genes, from which 3044 are protein coding, 52 are non-coding RNAs, and 11 are pseudogenes. Several phosphatases such as alkaline phosphatases and pyrophosphatases were mined from the genome. Further genomic study (phylogenetics, sequence analysis, and functional mechanism) and experimental data suggested that the alkaline phosphatase produced by R. marina could potentially be utilized in promoting plant growth, particularly for plants on saline-based agricultural land.


[Blood platelets: neuronal model in psychiatric disorders].
There are some evidences to propose blood platelets as a model of bioaminergic neurons. Similarities between platelets and neurons are particularly important with respect to serotonin metabolism but now it is possible to extend this model to other neurotransmitters such as dopamine, GABA, glutamate... The reason for these similarities may be due to the common embryonic origin of these two very different cell types. Some changes of platelet functions are observed in psychiatric syndromes. For example: serotonin uptake, bioamine storage, enzymatic activities are modified in different types of depression and schizophrenia, infantile autism, neurologic diseases (migraine, chorea, Down syndrom). Furthermore, psychotropic drugs also alter the platelet functions. Recently, the discovery of neuro-endocrine disorders in psychiatric diseases has led to the proposal of platelets as a model in neuro-endocrinology. Some arguments can be developed to support this hypothesis. In biological psychiatry, the platelet model seems actually useful essentially in the classification of psychiatric diseases, the management of treatments and the study of new psychotropic drugs. However methodologic difficulties still presently limit the development of this model.


Increase in DNA single-strand break rejoining by continuous exposure of human mononuclear blood cells to radioiodine ((131)I) in vitro.
Radioiodine ((131)I) induced a dose- and time-dependent increase in DNA single-strand breaks (DNA-ssb) in human (G0) mononuclear blood cells (MNC) in vitro. Incubation of MNC with 22MBq (131)I/ml at 4 degrees C caused a linear, time-dependent induction of DNA-ssb (increase in elution rate: 24.7 x 10(-3) h(-1) per 100 min incubation with (131)I). However, if MNC were incubated at 37 degrees C a decrease in the slope of the time effect curve was observed after about 300 min incubation with 22 or 30 MBq (131)I/ml. The goodness of fit of different regression models was assessed by Akaike's Information Criterion (AIC). The best fit was obtained for a non-linear model (y=a+bx+cx(0.5); AIC=53.5; where x is incubation time and y is elution rate), whereas other models including the linear regression model y=a+bx; AIC=38.6) were worse. As the total induction of DNA-ssb at 4 degrees C was constant with time, the decrease in the slope of the time effect curve (DNA-ssb versus time) at 37 degrees C can be interpreted as an increase in rejoining of DNA-ssb. Inhibition of both RNA and protein synthesis clearly increased the extent of DNA-ssb observable after incubation with (131)I. Thus, during continuous exposure of MNC to (131)I, proteins were synthesized which rejoined DNA-ssb. However, incubation of MNC with (131)I (44 MBq/ml) at 37 degrees C under conditions expected to lead to inhibition of RNA and/or protein synthesis still resulted in a decrease of the slope of the time effect curve, indicating a stimulation of DNA-ssb rejoining. Thus, we favour the hypothesis that the increase in the activity of DNA-ssb rejoining, besides de novo synthesis of repair enzymes, is also caused by a post-translational stimulation of DNA-repair enzymes and that this stimulation possibly is mediated by DNA-fragments.


Antibodies to Epstein-Barr virus and cytomegalovirus in primary Sjogren's syndrome.
Sera from 28 patients with Primary Sjögren's Syndrome (SS) and 20 healthy subjects were tested for the presence of antibodies to Epstein-Barr Virus (EBV) and Cytomegalovirus (CMV). No difference was noted in the mean titre of anti-CMV antibodies in patients and in controls. For what concerns EBV, the mean titre of anti-EBNA antibodies was significantly higher in SS patients than in normals (p less than 0.001); moreover, within the SS population, titres were higher in SSB-positive than in SSB-negative patients (p less than 0.05). These results, together with the fact that anti-SSB antibodies (characteristic of Sjögren's Syndrome) recognize also two EBV-encoded RNAs, strengthen the hypothesis that EBV is involved in the pathogenesis of SS.


Studies of HIV-1 protease inhibitors. I. Incorporation of a reduced peptide, simple aminoalcohol, and statine analog at the scissile site of substrate sequences.
Inhibitors of the protease of human immunodeficiency virus type-1 (HIV-1) were designed and synthesized. A reduced peptide, simple aminoalcohol, and statine analog, 4-amino-3-hydroxy-5-phenylpentanoic acid (AHPPA), were inserted at the scissile site of substrate sequences of HIV-1 protease. While both reduced peptides and simple aminoalcohol derivatives were weak inhibitors, the peptides containing AHPPA demonstrated moderate inhibitory activity. The more potent alcohol configuration of AHPPA is (R), which is opposite to the configuration in potent inhibitors of other aspartic proteases. In particular, compound 28 ((3R,4S)-4-(N-tert-butoxycarbonyl- L-glutaminyl-L-asparaginyl)amino-3-hydroxy-5-phenylpentanoic acid 2'-methylbutylamide) had a Ki of 0.36 microM and exhibited excellent enzyme specificity.


Thrombus versus wall biological activities in experimental aortic aneurysms.
The intraluminal thrombus (ILT) is considered to participate in abdominal aortic aneurysm (AAA) evolution. To assess whether this role proceeds via ILT influence on biological activity of the AAA wall, we studied the relationships between the levels of some relevant proteases and microparticles (MP) released by ILT versus wall in rat experimental AAAs. Two weeks after elastase perfusion, ILT and AAA wall were incubated in cell culture medium and studies were performed on conditioned media. As shown by gelatin zymography, ILT released higher amounts of MMP9 than the wall, whereas the level of MMP2 activation (active/pro) was similar. Levels of elastase and urokinase plasminogen activator, plasmin and MPs, determined, respectively, by casein zymography, substrate hydrolysis and flow cytometry, were higher in ILT than in wall. Aneurysm diameter positively correlated with wall MMP9 levels, MMP2 activation, plasmin activity and MP release. Moreover, wall and ILT levels of pro- and active forms of MMP2, elastase and plasmin were positively correlated. Wall levels of MMP2 activation and plasmin activity also correlated with ILT weight. The present data suggest that, in this experimental model, ILT may contribute to AAA evolution via its influence on the level of aneurysmal wall protease activity.


Rheumatoid arthritis following PEG-interferon-alfa-2a plus ribavirin treatment for chronic hepatitis C: a case report and review of the literature.
The combination of Pegylated Interferon-alpha (PEG-IFN-α) and ribavirin is the current standard of care for the treatment of HCV infection. Unfortunately, IFN-α may lead to the induction or exacerbation of autoimmune diseases, such as psoriasis, thyroiditis, systemic lupus erythematosus and, rarely, rheumatoid arthritis (RA). We report the case of a man affected with chronic hepatitis C (CHC) due to HCV genotype 3a infection, who developed RA after a complete course of PEG-IFN-α and ribavirin. Nine weeks after cessation of antiviral treatment, the patient developed symmetrical polyarthritis, with pain and edema in the wrists, knees, shoulders and metacarpophalangeal joints; magnetic resonance imaging detected initial bone erosions with juxta-articular osteopenia in wrist, knee and hand joints. Anti-cyclic citrullinated peptide (anti-CCP) antibodies were positive. Autoimmune diseases, including RA, may occur when treating chronic hepatitis C with PEG-IFN-α and ribavirin; therefore, a close surveillance for the occurrence of autoimmune phenomena should be suggested in the setting of HCV management.


Meat intake and cooking techniques: associations with pancreatic cancer.
Heterocyclic amines (HCAs), and polycyclic aromatic hydrocarbons (PAHs), formed in temperature and time-dependent manners during cooking of meat, may increase the risk of certain cancers. As these compounds could be carcinogenic for the pancreas, we assessed meat intake, preparation methods, and doneness preferences as risk factors for exocrine pancreatic cancer. In a case-control study (cases=193, controls=674), subjects provided information on their usual meat intake and how it was cooked, e.g. fried, grilled or barbecued (BBQ), etc. Meat doneness preferences were measured using photographs that showed internal doneness and external brownness with a numerical scale. Data were analyzed with unconditional logistic regression. Odds ratios (ORs) increased with increased intake of grilled/BBQ red meat in an analysis adjusted for age, sex, smoking, education, race, and diabetes. Based on amount of BBQ meat consumed, the OR and 95% confidence interval (CI) for the fifth quintile relative to the reference group (quintiles 1 and 2) was 2.19 (1.4, 3.4). Findings were not substantively changed by further adjustment for calories, total fat, fruit and vegetables, or alcohol consumption (from a food frequency questionnaire (FFQ)). Other meat variables did not show statistically significant associations with risk nor did they substantively alter the findings for BBQ. These included total meat, processed meat, total red meat, total white meat, total broiled meat, total fried meat, or total meat cooked by means other than grilling. We conclude that grilled red meat intake is a risk factor for pancreatic cancer and that method of meat preparation in addition to total intake is important in assessing the effects of meat consumption in epidemiologic studies.


Detection of a trailing (L5) Neptune Trojan.
The orbits of small Solar System bodies record the history of our Solar System. Here, we report the detection of 2008 LC18, which is a Neptune Trojan in the trailing (L5) Lagrangian region of gravitational equilibrium within Neptune's orbit. We estimate that the leading and trailing Neptune Trojan regions have similarly sized populations and dynamics, with both regions dominated by high-inclination objects. Similar populations and dynamics at both Neptune Lagrangian regions indicate that the Trojans were likely captured by a migrating, eccentric Neptune in a dynamically excited planetesimal population.


Polymorphism between HLA-A*0301 and A*0302 located outside the pocket F alters the PΩ peptide motif.
The human leukocyte antigen (HLA)-A*03 group has more than 90 known members and is one of the largest families of HLA class I alleles, with the most common variant being HLA-A*0301. In this study, we determined the peptide-binding motif of the highly frequent Sudanese allele A*0302 and compared it with the previously published peptide-binding motif of A*0301. The two alleles differ only at two distinct residues Glu152Val and Leu156Gln, which are predicted to be part of specificity pockets D, C and E and thus in contact with the peptide. Soluble recombinant A*0302 was expressed, affinity purified and the bound peptides were then eluted and analysed by mass spectrometry. The peptide-binding motif of A*0302 differs significantly from the previously published HLA-A*0301 and the Glu152Val/Leu156Gln mismatches appear to have a significant impact on the peptide-binding features of A*0302 and A*0301.


100th anniversary of the discovery of insulin perspective: insulin and adipose tissue fatty acid metabolism.
Insulin inhibits systemic nonesterified fatty acid (NEFA) flux to a greater degree than glucose or any other metabolite. This remarkable effect is mainly due to insulin-mediated inhibition of intracellular triglyceride (TG) lipolysis in adipose tissues and is essential to prevent diabetic ketoacidosis, but also to limit the potential lipotoxic effects of NEFA in lean tissues that contribute to the development of diabetes complications. Insulin also regulates adipose tissue fatty acid esterification, glycerol and TG synthesis, lipogenesis, and possibly oxidation, contributing to the trapping of dietary fatty acids in the postprandial state. Excess NEFA flux at a given insulin level has been used to define in vivo adipose tissue insulin resistance. Adipose tissue insulin resistance defined in this fashion has been associated with several dysmetabolic features and complications of diabetes, but the mechanistic significance of this concept is not fully understood. This review focusses on the in vivo regulation of adipose tissue fatty acid metabolism by insulin and the mechanistic significance of the current definition of adipose tissue insulin resistance. One hundred years after the discovery of insulin and despite decades of investigations, much is still to be understood about the multifaceted in vivo actions of this hormone on adipose tissue fatty acid metabolism.


Nanoplasmonics in Paper-Based Analytical Devices.
Chemical and biological sensing are crucial tools in science and technology. Plasmonic nanoparticles offer a virtually limitless number of photons for sensing applications, which can be available for visual detection over long periods. Moreover, cellulosic materials, such as paper, represent a versatile building block for implementation of simple, yet valuable, microfluidic analytical devices. This mini review outlines the basic theory of nanoplasmonics and the usability of paper as a nanoplasmonic substrate exploiting its features as a (bio)sensing platform based on different mechanisms depending on localized surface plasmon resonance response. Progress, current trends, challenges and opportunities are also underscored. It is intended for general researchers and technologists who are new to the topic as well as specialist/experts in the field.


Computed tomography in total coronary occlusions (CTTO registry): radiation exposure and predictors of successful percutaneous intervention.
There is no mention in the current "appropriateness criteria for CTCA" of the need of CTCA investigation prior to an attempt at recanalisation of a CTO. To define better the role of CTCA in the treatment of patients with CTOs, we performed CTCA in a consecutive cohort of eligible patients who were scheduled for percutaneous recanalisation of a CTO. Symptomatic patients due to a CTO suitable for percutaneous treatment were included. One hundred and thirty-nine (142 CTOs) patients were studied. Overall success rate was 62.7%. By CTCA, the occlusion length was 24.9 +/- 18.3 vs. 30.7 +/- 20.7 mm in successful and failed cases (p = 0.1), but the frequency of patients with an occlusion length >15 mm was different, i.e., 63.2% vs. 82.7%, respectively (p = 0.02). Severe calcification, (> 50% CSA) was more prevalent in failed cases (54.7% vs. 35.9%, p = 0.03). Calcification at the entry of the occlusion was present in 58.5% of the failures vs. 41.6% of the successful cases (p = 0.04), while calcium at the exit was not different. The length of calcification was 8.5 +/- 8.4 vs. 5.5 +/- 6.6 mm in the failed and successful cases respectively (p = 0.027). By multivariable analysis, the only independent predictor of procedural success was the absence of severe calcification as defined by CTCA. The mean effective radiation dose of the PCI was 39.3 +/- 30.1 mSv. The mean effective radiation dose of CT scan was 22.4 mSv: 19.2 +/- 6.5 mSv for contrast-enhanced scan, 3.2 +/- 1.7 mSv for calcium scoring scan. More severe calcified patterns, as assessed by CTCA, are seen in failed cases. The radiation exposure during a CT scan prior to a CTO PCI is considerable, and further studies are required to determine whether this extra diagnostic study is warranted.


A major gibberellic Acid-induced barley aleurone cysteine proteinase which digests hordein : purification and characterization.
We previously described the purification and characterization of a 37,000 M(r) cysteine proteinase, designated EP-A, from gibberellic acid (GA(3))-induced barley (Hordeum vulgare L.) aleurone layers (S Koehler, T-HD Ho [1988] Plant Physiol 87: 95-103). A second, more abundant protease has now been purified from this tissue. This protease, designated EP-B, has an apparent M(r) of 30,000 on 10% sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). It resolves into two bands during native isoelectric focusing with pl of 4.6 to 4.7. The analysis of hemoglobin digestion products by both gradient SDS-PAGE and Bio-Gel P2 chromatography, the inhibition of protease activity by E-64, leupeptin, iodoacetate, and p-hydroxymercuribenzoate, and N-terminal amino acid sequence analysis all indicate that EP-B is a cysteine proteinase. The first 22 amino acids at the N terminus of EP-B have been determined, and their sequence is 90% similar to that of EP-A. EP-B has properties similar to EP-A; however, EP-B is much more sensitive to high pH during gel electrophoresis and therefore is not detectable on native activity gels used to detect EP-A. Its pH optimum against azocasein and hemoglobin is 4.5 to 4.6. Both of these proteinases digest hordeins enriched for the B and D fractions into similar peptides of 25,000 to 2,000 M(r) as determined by gradient SDS-PAGE.


Fourier domain interpretation of real and pseudo-moiré phenomena.
Unified interpretation for the real and pseudo moiré phenomena using the concept of biased and unbiased frequency pairs in the Fourier spectrum is given. Intensity modulations are responsible for pseudo moiré appearance in the image plane rather than average intensity variations dominating real moiré. Detection of pseudo moiré necessitates resolving superimposed structures in the image plane. In the case of the product type superimposition generating both real and pseudo moiré, our interpretation utilizes the Fourier domain information only. The moiré pattern characteristics such as an effective carrier, modulation and bias intensity distributions can be readily predicted. We corroborate them using two-dimensional continuous wavelet transform and fast adaptive bidimensional empirical mode decomposition methods as complementary image processing tools.


[Type 2 diabetes and anti-inflammatory agents: new therapeutic prospects?].
It is now well accepted that a chronic, low-grade inflammation is observed in abdominal obesity, insulin resistance and type 2 diabetes mellitus, and that pro-inflammatory cytokines and oxidative stress play a role in the pathogenesis of type 2 diabetes. These new findings raise the question of whether antiinflammatory strategies may have a place in the prevention and treatment of type 2 diabetes. This review article describes the results obtained in studies on patients with metabolic syndrome or type 2 diabetes aiming to test the metabolic effect of anti-inflammatory (salicylates, antagonists of interleukine-1, antagonists of tumor necrosis factor-alpha) and anti-oxydants (succinobucol) drugs.


Proteolytic cleavage reveals interaction patterns between silica nanoparticles and two variants of human carbonic anhydrase.
To characterize the sites on the protein surface that are involved in the adsorption to silica nanoparticles and the subsequent rearrangements of the protein/nanoparticle interaction, a novel approach has been used. After incubation of protein with silica nanoparticles for 2 or 16 h, the protein was cleaved with trypsin and the peptide fragments were analyzed with mass spectrometry. The nanoparticle surface area was in 16-fold excess over available protein surface to minimize the probability that the initial binding would be affected by other protein molecules. When the fragment patterns obtained in the presence and absence of silica nanoparticles were compared, we were able to characterize the protein fragments that interact with the surface. This approach has allowed us to identify the initial binding sites on the protein structure and the rearrangement of the binding sites that occur upon prolonged incubation with the surface.


Associations Between Acculturation, Depressive Symptoms, and Life Satisfaction Among Migrants of Turkish Origin in Germany: Gender- and Generation-Related Aspects.
The aim of the present study was to investigate the degree of depressive symptoms and life satisfaction (LS) as well as the association between acculturation and depressive symptoms among a large sample of persons with Turkish migration background in Germany, taking into account gender- and migration-related differences. This study was part of a pretest for a large national epidemiological cohort study in Germany. Acculturation was measured using the Frankfurt Acculturation Scale (FRACC). Based on the median split of the two subscales, four acculturative styles according to Berry (integration, assimilation, separation and marginalization) were determined. Depressive symptoms were assessed with the depression module (PHQ-9) from the Patient Health Questionnaire. LS was assessed with a single item on a scale from 1 = bad to 5 = excellent. Differences in levels of depressive symptoms and LS in relation to gender and generation of migration were tested with analysis of covariance, controlling for age. Gender-stratified multiple linear regression analyses were also conducted for depressive symptoms as criterion variable. 328 Turkish migrants participated (61.3% women). The cut-off-value of ≥10 for the PHQ-9 was achieved by 33.2% of the women and 26.4% of the men (p=0.209, φ=0.071). In female migrants, the age-adjusted mean score for depressive symptoms was 7.81 (SD=6.42), in males 6.70 (SD=6.41) (p=0.137, η2=0.007). After controlling for unemployment status, women showed a trend for being more frequently depressed than men (p=0.055, φ=0.117) and also demonstrated a trend for higher levels of depressive symptoms (p=0.072, η2=0.012). No significant gender-specific difference was found concerning age-adjusted mean score for LS (p=0.547, η2=0.001), also when controlled for unemployment status (p=0.322, η2=0.004). In both sexes, the second generation demonstrated a significantly higher age-adjusted mean score for LS of small/medium effect size than the first generation. In women, separation as acculturation style (linear regression coefficient (B=4.42, 95% CI=1.68, 7.17, p=0.002; reference: integration), having no partnership (B=2.56, 95% CI=0.26, 4.86, p=0.03) and lower education (B=-2.28, 95% CI=-4.54, -0.02, p=0.048) were associated with higher severity of depressive symptoms; in men, separation as acculturation style (B=4.01, 95% CI=0.70, 7.31, p=0.018; reference: integration) and employment status (B=-3.32, 95% CI=-5.71, -0.92, p=0.007) were related to depression levels. Separation as acculturation style is associated with higher levels of depressive symptoms (for both genders). Gender-sensitive health promotion programs should target separated migrants to improve their integration into the German society.


On the use of acridinium indicators for the chemiluminescent determination of the total antioxidant capacity of dietary supplements.
Acridinium salts, due to their chemiluminogenic properties, have found several applications in biomedical analysis as labels and indicators, where the assessment of emission intensity is used for the end-point detection. This work presents the use of chemiluminescent indicators in the form of selected acridinium esters in order to determine the antioxidant properties of exemplary formulations, namely quercetin, vitamin C and the dietary supplement, Apiextract. The principle of measurements is based on a change in the kinetics of emission decay derived from the acridinium cations in alkaline solutions of hydrogen peroxide in the presence of an antioxidant (the analyte). The proposed system makes a beneficial alternative to related methods, which mostly rely on the assessment of emission efficiency and use the luminometric standard luminol - due to superior parameters of acridinium chemiluminescence, among others - high temporary emission efficiency. The features of the proposed method are manifested by a shorter time period of analysis and lower background signals associated with the environmental influences, as compared to typical approaches. The chromatographic (RP-HPLC) analyses of the substrates and products generated during chemiluminogenic oxidation of acridinium cations under assay conditions are also presented.


Is a web-based concordance test feasible to assess therapeutic decision-making skills in a French context?
At the end of undergraduate medical curriculum, a written simulation-based examination is used in France to assess therapeutic decision-making skills and to rank students for the purpose of matching their training specialties. However, this examination based on a single assessment method remains a subject of debate. To study the feasibility of a web-based Concordance test for therapeutic decision-making assessment. A 12 clinical-case Concordance test was developed based on objectives for the undergraduate training program. The test was administered on line to candidates with different levels of clinical experience. Fifteen therapeutic teachers constituted the reference panel. Data analysis included analysis of variance, post-hoc test, and Cronbach's alpha. One hundred and seventy participants (113 students, 34 residents, 23 physicians) fully completed the free-access test on line with no technical problems. Differences between the mean scores for groups were significant (p < 0.001). Significant differences occurred between fourth year students and residents (p < 0.001), fourth year students and physicians (p = 0.001). No difference was found between residents and physicians. Reliability coefficient was 0.67. A web-based Concordance test in the field of therapeutic decision-making was considered feasible in a French learning environment. Further research is warranted to determine its usefulness as a part of the National Examination.


CREB activation induces adipogenesis in 3T3-L1 cells.
Obesity is the result of numerous, interacting behavioral, physiological, and biochemical factors. One increasingly important factor is the generation of additional fat cells, or adipocytes, in response to excess feeding and/or large increases in body fat composition. The generation of new adipocytes is controlled by several "adipocyte-specific" transcription factors that regulate preadipocyte proliferation and adipogenesis. Generally these adipocyte-specific factors are expressed only following the induction of adipogenesis. The transcription factor(s) that are involved in initiating adipocyte differentiation have not been identified. Here we demonstrate that the transcription factor, CREB, is constitutively expressed in preadipocytes and throughout the differentiation process and that CREB is stimulated by conventional differentiation-inducing agents such as insulin, dexamethasone, and dibutyryl cAMP. Stably transfected 3T3-L1 preadipocytes were generated in which we could induce the expression of either a constitutively active CREB (VP16-CREB) or a dominant-negative CREB (KCREB). Inducible expression of VP16-CREB alone was sufficient to initiate adipogenesis as determined by triacylglycerol storage, cell morphology, and the expression of two adipocyte marker genes, peroxisome proliferator activated receptor gamma 2, and fatty acid binding protein. Alternatively, KCREB alone blocked adipogenesis in cells treated with conventional differentiation-inducing agents. These data indicate that activation of CREB was necessary and sufficient to induce adipogenesis. Finally, CREB was shown to bind to putative CRE sequences in the promoters of several adipocyte-specific genes. These data firmly establish CREB as a primary regulator of adipogenesis and suggest that CREB may play similar roles in other cells and tissues.


The effect of simultaneous exposure to cigarette smoke and noise on distortion product otoacoustic emissions in rats.
Cigarette smoking is a possible risk factor for hearing loss. However, the impact of simultaneous exposure to noise and smoke on hearing has remained controversial. This study investigated the combined effect of exposure to cigarette smoking and noise on hearing loss. Three groups of male Wistar rats (275 ± 25 g) were subjected to white noise (102 ± 0.5 dB), cigarette smoking (20 cigarettes), and both cigarette smoking and noise for 8 h and 10 days inside the exposure chamber. The control group was exposed to neither noise nor smoke. Distortion product otoacoustic emissions (DPOAE) were measured before any intervention, and it was repeated 1, 7, and 21 days after the last exposure. One-day postexposure to noise, cigarette smoking, and both cigarette smoking and noise, the mean of DPOAE amplitudes decreased significantly ( p < 0.05) between, respectively, 5.7-30.7, 1.5-7.5, and 5.2-32.6 dB within the frequency range of 4620-9960. Temporal DPOAE change in rats exposed to noise or both cigarette smoking and noise was not significantly different ( p > 0.05). DPOAE amplitudes returned to the baseline values in the group subjected to smoking 21 days postexposure. The most permanent change was observed in rats exposed to both cigarette smoking and noise. Accordingly, simultaneous subacute exposure to noise and cigarette smoking increases the effect of noise on permanent hearing loss. Therefore, smoking workers exposed to noise might be at a greater risk of developing hearing loss, and it is recommended that authorities in charge take note of this evidence.


Impairment of the selenoenzyme type I iodothyronine deiodinase in C3H/He mice.
Type I iodothyronine deiodinase (ID-I) activity is impaired in C3H/He (C3H) mice compared with BALB/c and C57BL/6N (C57) mice. In this study we compared ID-I activity and protein labeling with N-bromoacetyl(-)[125I]T3 (BrAc[125I]T3) or 75Se in liver microsomes of C3H and C57 mice. Hepatic ID-I activity in C3H mice was highly variable with a median of only 18% of that in C57 mice. However, C3H mice had normal serum T4 and T3 levels, although serum reverse T3 was increased. The 28-kilodalton (kDa) ID-I protein was identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of BrAc[125I]T3-labeled microsomes. Labeling of this protein was virtually undetectable in C3H samples with low enzyme activity. ID-I activity in liver microsomes was strongly decreased in Se-deficient mice, which was paralleled by a drastic decrease in BrAc[125I]T3-labeling of the 28-kDa band compared with control mice. Labeling of ID-I with 75Se was demonstrated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of liver microsomes of [75Se]selenite-injected mice. 75Se labeling of the 28-kDa band was markedly higher in Se-deficient than in control mice and was also markedly higher in C57 than in C3H mice. Finally, liver ID-I messenger RNA (mRNA) was measured on Northern blots using a rat ID-I complementary DNA probe. Messenger RNA levels correlated strongly with ID-I activity, showing a significant decrease in C3H mice. We conclude that in mice, like in rats and humans, ID-I is a selenoprotein. ID-I activity is impaired in C3H mice because of decreased transcription of the ID-I gene or reduced stability of the mRNA.


The association between the incidence of urolithiasis and nutrition based on Japanese National Health and Nutrition Surveys.
To clarify the association between regional variations in urolithiasis incidence and nutrition intake, we evaluated associated data from Japanese national surveys. The incidence of urolithiasis in 12 regions of Japan was calculated from 2005 patient data obtained from 430 hospitals (n = 92,797). Nutrition intake data were obtained from the National Health and Nutrition Survey. We examined the association between urolithiasis incidence and average intake of various types of food or nutrients by region. Continuing surveys in Japan reveal fixed variations in urolithiasis incidence among geographic regions. The national average of patients with urolithiasis was estimated as 203.1 per 100,000 citizens. Regarding food, intake of fruit correlated negatively with the incidence of urolithiasis (r = -0.721, p = 0.008), while intake of eggs (r = 0.537, p = 0.072) and sugar (r = 0.475, p = 0.119) tended to positively correlate with incidence. Regarding nutrients, intake of potassium (r = -0.500, p = 0.098), vitamin K (r = -0.562, p = 0.057), and pantothenic acid (r = -0.560, p = 0.058) tended to negatively correlate with incidence. The incidence of urolithiasis is higher in geographic areas with populations having low fruit and high sugar intake.


Processing line location and orientation.
For stimulus dimensions of line location and orientation with both card-sorting and discrete reaction-time trials, facilitation occurred when dimensions were positively correlated, and interference appeared when dimensions varied orthogonally. Interference could not be attributed to differential sensory accrual arising from positional uncertainty or to a repetition-effects advantage for control over orthogonal conditions. Facilitation tended to disappear when the same response was not required for the two dimensions, and when competing responses were required, interference appeared with redundant dimensions (negatively correlated stimulus sets). These data seem consistent with a model that calls for automatic and parallel extraction of features and their locations, with facilitation-interference effects having their locus in postperceptual response processing.


Safety of modified vaccinia virus Ankara (MVA) in immune-suppressed macaques.
Modified vaccinia virus Ankara (MVA)-based recombinant viruses have been shown to be potent vaccine candidates for several infectious and neoplastic diseases. Since a major application of these live, replication-deficient vectors would be their use in immunocompromised or potentially immunocompromised individuals, a preclinical safety study was carried out. Macaques were inoculated with high doses of MVA (10(9)) via various routes, after immune-suppression by total-body irradiation, anti-thymocyte globulin treatment, or measles virus (MV) infection. No clinical, haematological or pathological abnormalities related to MVA inoculation were observed during a 13-day follow-up period. The presence of MVA genomes was demonstrated by nested PCR during the course of the experiment in all macaques, but from none of these animals replication competent MVA could be reisolated. These data suggest that MVA can safely be used as a basis for recombinant human vaccines, and that it is also safe for use in immunocompromised individuals.


[Gastrointestinal system tumors in Italian emigrants].
In this paper we present the risk of death for stomach, colon, rectum and pancreas cancers in Italian migrants to Canada, Argentina, Australia, France and England and Wales. Estimations of relative risks (RR) in Italian migrants, in residents in Italy and in Southern Italy relative to the local born in the host country are shown. Relative risks in Italian migrants to Australia were analysed also by duration of stay in the host country. The Italian migrants' cancer profile in intermediate between the origin and the host population: a reduction of risk of death for stomach cancer and an increase of risk for colorectal cancers are the main results. The results are discussed taking into account the analysis by duration of residence and the pattern of food prevalent in the different countries considered.


Toward identification of acid/base catalysts in the active site of enolase: comparison of the properties of K345A, E168Q, and E211Q variants.
High-resolution crystallographic data show that Glu 168 and Glu 211 lie on opposite surfaces of the active site from Lys 345. Two different proposals for general base catalysis have emerged from these structural studies. In one scheme, the carboxylate side chains of Glu 168 and Glu 211 are proposed to ionize a trapped water molecule and the OH- serves as the base [Lebioda, L., & Stec, B. (1991) Biochemistry 30, 2817-2822]. In the other proposal, the epsilon-amino group of Lys 345 functions in general base catalysis [Wedekind, J. E., Poyner, R. R., Reed, G. H., & Rayment, I. (1994) Biochemistry 33, 9333-9342]. Genes encoding site specific mutations of these active site residues of yeast enolase, K345A, E168Q, and E211Q, have been prepared. The respective protein products of the wild type and mutant genes were expressed in Escherichia coli and isolated in homogeneous form. All three mutant proteins possess severely depressed activities in the overall reaction- < 1 part in 10(5) of wild type activity. Properties of the three mutant proteins in partial reactions were examined to define more clearly the roles of these residues in the catalytic cycle. The K345A variant fails to catalyze the exchange of the C-2 proton of 2-phospho-D-glycerate with deuterium in D2O, whereas both the E211Q and E168Q mutant proteins are functional in this partial reaction. For E211Q and E168Q enolases, exchange is essentially complete prior to appearance of product, and this observation provides further support for an intermediate in the normal reaction. K345A enolase is inactive in the ionization of tartronate semialdehyde phosphate (TSP), whereas both E168Q and E211Q proteins alter the tautomeric state or catalyze ionization of bound TSP. Wild type enolase catalyzes hydrolysis of (Z)-3-chloro-2-phosphoenolpyruvate by addition of OH- and elimination of Cl- at C-3. This reaction mimics the addition of OH- to C-3 of phosphoenolpyruvate in the reverse reaction with the normal product. All three mutant proteins are depressed in their abilities to carry out this reaction. In single-turnover assays, the activities vary in the order K345A > E168Q >> E211Q. These results suggest that Lys 345 functions as the base in the ionization of 2-PGA and that Glu 211 participates in the second step of the reaction.


Isolated sleep paralysis in African Americans with panic disorder.
Isolated sleep paralysis (ISP) was assessed in African Americans and Whites diagnosed with panic disorder and other anxiety disorders. Participants were recruited from an outpatient clinic where they were diagnosed with panic disorder, generalized anxiety disorder, obsessive-compulsive disorder, social phobia, and simple phobia. Control groups of volunteers without a history of psychiatric disorder were included. All research participants completed a questionnaire to assess for ISP. Group differences were analysed through a series of chi-square analyses. The incidence of recurrent ISP was significantly higher in African Americans with panic disorder (59.6%) as compared with African Americans with other anxiety disorders (11.1%), African American control group participants (23%), Whites with panic disorder (7.5%), Whites with other anxiety disorders (0%), and White control group participants (6%). Recurrent ISP was found to be more common among African American participants, particularly for those with panic disorder. African Americans with panic disorder may experience recurrent ISP as a feature of their disorder.


Correlation between the laryngeal brain stem evoked response and the laryngeal chemoreflex in the porcine model.
The laryngeal brain stem evoked response (LBR) represents the neural activity involved in laryngeal reflex pathways. The laryngeal chemoreflex (LCR) is a centrally mediated response consisting of apnea and hemodynamic changes that result from laryngeal stimulation. The purpose of this study is to determine the characteristics of the LBR that are predictive of LCR severity in the porcine model. The duration of apnea resulting from stimulation of the supraglottic larynx defined LCR severity. The LBR tracings were recorded from electrodes flanking the brain stem following direct electrical stimulation of the superior laryngeal nerve. The LBR peak latencies from piglets demonstrating prolonged LCR apnea were compared to those without an exaggerated LCR response. Two LBR peak latencies demonstrated a statistically significant difference between the two piglet groups. These peak latencies appear to be indicators of susceptibility to exaggerated laryngeal reflex sensitivity. Thus, the LBR may prove useful in identifying and evaluating subjects predisposed to conditions associated with dysfunctional laryngeal reflex activity.


[Continuities and changes in Swiss migration policy].
"In May 1991 the Swiss Federal Government...submitted to the Parliament some proposals aiming at reshaping the immigration policy. In this article, we give an overview of the current re-organisation of policy, we analyse the underlying logic of the adopted measures as well as their possible consequences, and we try to show how the policy towards foreigners interferes with the policy towards refugees and asylum-seekers. We describe the political and economic motivations behind the changes in policy.... We show how immigration policy and asylum policy have become gradually incompatible.... The contradiction is obvious in three aspects of the current policy: the ethnic selection, the selection according to occupations, and the legitimation of the selection." (SUMMARY IN ENG)