Calorie restriction reverses age-related alteration of cavernous neurovascular structure in the rat.
Calorie restriction (CR) refers to a reduction of calorie intake without compromising essential nutrients to avoid malnutrition. CR has been established as a non-genetic method of altering longevity and attenuating biological changes associated with aging. Aging is also an important risk factor for erectile dysfunction. The aim of this study was to examine whether CR diet can reverse the age-related alterations of erectile tissue in the aged rat. Four groups of rats were used: young rats (7 months) + ad libitum, aged rats (22 months) + ad libitum, young rats + CR diet, and aged rats + CR diet. The ad libitum group had free access to both food and water, and CR groups were fed 60% of the food intake of their ad libitum littermates, starting from 6 weeks before sacrifice. The penis was harvested and stained with antibodies to von Willebrand factor, smooth muscle α-actin, platelet-derived growth factor receptor-β, phospho-eNOS, nNOS, and neurofilament. We also performed Masson trichrome staining and TUNEL assay. The blood samples were collected for the measurement of serum total testosterone level. The contents of endothelial cells, smooth muscle cells, pericytes, and neuronal cells as well as serum testosterone levels were significantly lower in the penis of aged rats than in their young littermates. CR significantly restored cavernous endothelial cells, smooth muscle cells, pericytes, and neuronal cell contents and decreased cavernous endothelial cell apoptosis and fibrosis in both young and aged rats. CR also increased serum testosterone level in aged rats, but not in young rats. CR successfully improved age-related derangements in penile neurovascular structures and hormonal disturbance. Along with a variety of lifestyle modifications, our study gave us a scientific rationale for CR as a non-pharmaceutical strategy to reprogram damaged erectile tissue toward neurovascular repair in aged men.


Chronic mesenteric volvulus in a dog.
A chronic, partial mesenteric volvulus was found on laparotomy of an adult Bernese mountain dog with a 4-month history of intermittent vomiting, diarrhea, and weight loss. The dog had elevated cholestatic and hepatocellular leakage enzymes, increased bile acids, azotemia, isosthenuria, and a hypokalemic, hypochloremic, metabolic alkalosis. The dog recovered fully following reduction of the volvulus.


Erythropoiesis-stimulating protein delivery in providing erythropoiesis and neuroprotection.
Erythropoietin (EPO), a glycoprotein, plays an important role in erythropoiesis and neuroprotection. EPO therapies for anemia or neurodegenerative diseases require frequent injections or high-dose systemic administration which may cause unwanted side effects. Various strategies for EPO delivery have been investigated for increasing EPO bioavailability and decreasing side effects, including nano/micro particles, PEGylation of EPO and transport-mediated delivery systems. Nano/micro particles provide EPO with long-term effect and protect EPO against proteolytic cleavage. PEGylated EPO prolong circulating time and reduce injection frequency of anemia treatment. A transport-mediated delivery system enables protein to cross biological barriers. Presently, there is no report about an effective delivery system of EPO for neuroprotection. This review focuses on EPO delivery systems for erythropoiesis or neuroprotection with prolonged duration and enhanced bioavailability.


Use of health care services by older Hispanics.
This paper presents information on regarding older Hispanics' use of health care services in an urban setting. Using the Comprehensive Assessment and Referral Evaluation (CARE) questionnaire, data on patterns of health care use and correlates of health services utilization were collected from a sample of 704 Hispanics age 60 and over residing in Los Angeles County. The results indicate that during the year preceding the interview, 79.4 per cent of the respondents saw a physician and 10 per cent were hospitalized. Of those seeing a doctor, 83.5 per cent saw a general practitioner and 32.6 per cent a specialist. When requiring medical care, respondents said that they would go to local private doctors (49.9%), hospitals (26.7%), neighborhood clinics (18.6%), and Mexico (2%). Further analysis revealed that some utilization measures varied significantly according to respondents' sociodemographic and economic correlates such as age, language, income, and availability of health insurance.


Gyrification-Inspired Highly Convoluted Graphene Oxide Patterns for Ultralarge Deforming Actuators.
Gyrification in the human brain is driven by the compressive stress induced by the tangential expansion of the cortical layer, while similar topographies can also be induced by the tangential shrinkage of the spherical substrate. Herein we introduce a simple three-dimensional (3D) shrinking method to generate the cortex-like patterns using two-dimensional (2D) graphene oxide (GO) as the building blocks. By rotation-dip-coating a GO film on an air-charged latex balloon and then releasing the air slowly, a highly folded hydrophobic GO surface can be induced. Wrinkling-to-folding transition was observed and the folding state can be easily regulated by varying the prestrain of the substrate and the thickness of the GO film. Driven by the residue stresses stored in the system, sheet-to-tube actuating occurs rapidly once the bilayer system is cut into slices. In response to some organic solvents, however, the square bilayer actuator exhibits excellent reversible, bidirectional, large-deformational curling properties on wetting and drying. An ultralarge curvature of 2.75 mm-1 was observed within 18 s from the original negative bending to the final positive bending in response to tetrahydrofuran (THF). In addition to a mechanical hand, a swimming worm, a smart package, a bionic mimosa, and two bionic flowers, a crude oil collector has been designed and demonstrated, aided by the superhydrophobic and superoleophilic modified GO surface and the solvent-responsive bilayer system.


[Congenital absence of the vagina--its diagnostic-therapeutic implications--case report].
Issues relating to diagnosis and reconstructive therapy for developmental anomalies of female genital tract are controversial. The teratogenic influence during the 6th week of intrauterine life, the time for the development of structures such as fallopian tube, uterus and cervix from the Müllerian duct may lead to their defective formation. In a 14 year old girl congenital absence of vagina, cervix developed right half of uterus (rudimentary horn?) and a pelvic kidney was diagnosed by laparoscopy and laparotomy. The attempt to connect uterus with the artificial vagina during the laparotomy was unfortunately not successful, the main reason being prolonged distance between the apex of artificial passage and the rudimentary uterus. In our opinion ultrasound is a superior diagnostic tool for diagnosis of developmental anomalies in comparison to the palpatory methods. The corrective and reconstructive surgery for the developmental anomalies of the female genital tract should be the domain of a specialized center. Increased awareness of the parents and the public, increase in environmental pollution has led to more frequent and earlier diagnosis of these malformations, which in turn has led to the shift in age for therapeutic interventions.


Virus inhibitory effect of combination of 9-(S)-(2,3-dihydroxypropyl) adenine and 6-azauridine.
Combination of 9-(S)-(2,3-dihydroxypropyl)adenine [(S)-DHPA] and 6-azauridine (AzUrd) is highly active in the selective inhibition of vaccinia virus in chick embryo cell culture. Synergic effect of this combination of compounds was not encountered in HeLa cell culture. Of the 17 analogues related to DHPA studied in this paper, 3 showed medium activity against vaccinia virus, but none of them was as effective as (S)-DHPA in combination with AzUrd.


Perineural local anesthetic treatments for osteoarthritic pain.
The most common disabling symptom of osteoarthritis (OA) is pain. Clinical investigations using disease-specific animal models have increased our insights into the pathophysiology of osteoarthritic pain. As the prevalence of OA continues to rise and current available treatment options give less than optimal levels of pain relief, opportunities to develop treatments to address osteoarthritic pain are increasing. Targeted administration of local anesthetics along sensory/motor nerves can provide an alternative strategy for managing osteoarthritic pain. Moreover, the development of engineered therapeutic drug delivery systems may allow for sustained perineural delivery of local anesthetics as opposed to the traditional intraarticular joint injections. This review presents an overview of 1) the pathophysiology of persistent pain associated with OA of the hip, shoulder, and knee and 2) the emerging therapeutic role of local anesthetics in providing analgesia for joint-related pain symptoms.


Imerslund-Gräsbeck anemia. A long-term follow-up study.
A follow-up study has been performed on 14 patients, now aged 6-46 years, with Imerslund-Gräsbeck anemia (congenital, hereditary selective malasorption of vitamin B12). On intramuscular vitamin B12 therapy, the patients are clinically and hematologically normal. Those who had constant proteinuria in childhood continue to excrete protein in the urine. Our patients excrete an average of 750 mg of protein per 24 hours (range 13-1460 mg). The proteinuria is predominantly of glomerular origin, but some is also of tubular origin. Renal biopsies of the two oldest patients were normal on light microscopy. Electron microscopy revealed moderate signs of chronic glomerulopathy of mesangioproliferative type in both patients. The renal lesions do not seem to be progressive.


Morphology and DNA barcoding reveal three species in one: description of Culicoides cryptipulicaris sp. nov. and Culicoides quasipulicaris sp. nov. in the subgenus Culicoides.
Species of the genus Culicoides (Diptera: Ceratopogonidae) are well known for their importance in the field of medical and veterinary entomology. Culicoides spp. transmit a wide variety of pathogens, primarily viruses that affect animals and humans. In Europe, the most economically important disease transmitted by Culicoides is bluetongue (BT). Culicoides spp. have been recently involved as primary vectors for Schmallenberg disease. The taxonomy within the subgenus Culicoides has been historically difficult and reorganizations have been proposed regularly. The subgenus Culicoides includes species that are considered to be potential vectors for BT. High morphological intraspecific variability has been attributed to these species. This highlights the apparent presence of previously undetected cryptic species diversity in the subgenus. In the present study, a detailed morphological and molecular study of specimens belonging to Culicoides pulicaris s.l. and specimens resembling a cross between C. pulicaris and Culicoides punctatus revealed the presence of two new species: Culicoides cryptipulicaris and Culicoides quasipulicaris. Females of C. quasipulicaris and males of both species were morphologically distinguished from C. pulicaris (Linnaeus, 1758), whereas females of C. cryptipulicaris were identified using molecular techniques exclusively.


Quality of life in cancer patients with different preferences for nurse spiritual therapeutics: The role of psychological capital.
To explore the status of quality of life and psychological capital and analyse the different effects of psychological capital on the quality of life of cancer patients with different preferences for nurse spiritual therapeutics. A cross-sectional survey was used. Two hundred and eight cancer patients were recruited using convenience sampling from a tertiary Chinese hospital, between March and July 2019. Data on preferences for nurse spiritual therapeutics (PNST), psychological capital (PsyCap) and quality of life (QoL) were collected using paper questionnaires. Hierarchical multiple regression was employed to investigate the different influences of PsyCap on QoL of cancer patients with various levels of PNST. Compared with patients having high PNST, patients with mild-moderate PNST experienced lower self-efficacy, hope, optimism, PsyCap and social/family well-being. PsyCap significantly explained the variance on QoL of patients with various levels of PNST. Age, gender, presence of caregiver were significant factors influencing physical, social/family and emotional well-being of patients with high PNST. The present study demonstrates disparities in PsyCap and QoL between cancer patients with mild-moderate and high PNST. It is essential to be aware of the positive influences of PsyCap on QoL and develop effective interventions for patients to improve their QoL, especially for those with mild-moderate PNST. It is necessary to realize the benefits of PsyCap on QoL of cancer patients with various levels of PNST. Appropriate training for nurses needs to be developed to promote their spiritual care competencies. Moreover, supportive interventions should be developed for cancer patients to improve their PsyCap and QoL.


Utility of immunochemistry in cytology.
The role played by cytology in primary diagnosis is undeniable. With improved management protocols and targeted therapy, the need for accurate diagnosis has become mandatory. Immunochemistry and molecular techniques are increasingly being used on limited tissue samples. This study was conducted to find out the impact of immunocytochemistry (ICC) on cytology material in cytology practice. Immunochemistry was done on alcohol-fixed smears and cell-block preparations. It was done with i6000 BioGenex autostainer using BioGenex reagents. A total of 148 cases occurring over a period of 3 years (September 2010-June 2013) were analyzed. Staining was done on cytology smears in 77 cases and on cell-block sections in 71 cases. ICC helped in diagnosis in 8 cases, confirmed the diagnosis in 26 cases, helped in subtyping in 60 cases, and helped in prognostication in 6 cases. ICC has altered the diagnosis in two cases. It was noncontributory in 43 cases, and the material was inadequate in three cases. In 102 cases (69%), ICC proved to be a useful adjunct in the diagnosis and prognostication; hence, its use is recommended in practice to aid in cytology services.


[Continuous production of anti-hepatitis B surface antigen monoclonal antibody in hollow fiber perfusion bioreactor].
Hybridoma cell line H440Ac was cultivated continuously in hollow fiber perfusion bioreactor for fifty days to produce anti-hepatitis B surface antigen (anti-HBsAg) monoclonal antibody. A total of 90 mg anti-HBsAg antibody was produced in the hollow fiber bioreactor with 1000 cm2 membrane surface area. The collected production medium has an average antibody concentration of 0.45 mg/ml with a high concentration of 2.3 mg/ml. This compares with 0.016 and 1.1 mg/ml antibody concentration as collected from spinner flask and mouse ascites. The purity of the produced antibody is 0.085, 0.0028 and 0.026 mg antibody per mg of total harvested protein in the culture media produced from the hollow fiber bioreactor, spinner flasks and mouse ascites, respectively.


Nutritional status of female athletes with subclinical eating disorders.
To assess the energy and nutritional status of female athletes with subclinical eating disorders and compare them with that of control subjects and standard norms. Group classification (subclinical eating disorder or control) was based on responses to a health and diet history questionnaire, a battery of self-report eating disorder questionnaires, and an in-depth interview. Energy and nutrient intakes and energy expenditure were determined by means of 7-day weighed food records and 7-day activity logs. Micronutrient status was assessed for iron, zinc, magnesium, vitamin B-12, and folate. Twenty-four female athletes with subclinical eating disorders and 24 female control athletes. Descriptive statistics were used to analyze demographic data. One-way analysis of variance was used to determine group differences in energy and nutrient intakes, energy balance, and blood values. Groups were similar in age, height, weight, fat-free mass, and body mass index. Mean energy intake was lower in the group with subclinical eating disorders (1,989 kcal/day) than in the control group (2,300 kcal/day; P=.004), whereas mean energy expenditures were similar (2,405 and 2,293 kcal/day, respectively). The group with subclinical eating disorders had significantly (P<.05) lower mean protein and fat intakes compared with the control group; mean micronutrient intakes were not significantly different. Mean status measures for iron, zinc, magnesium, vitamin B-12, and folate were within the normal ranges for both groups and no differences were noted between the groups. A similar number of athletes within each group used vitamin/mineral supplements < or = 4 times per week. Although female athletes with subclinical eating disorders had dietary intakes of energy, protein, carbohydrate, and certain micronutrients that were below recommended levels, micronutrient status appeared relatively unaffected, probably due to their use of supplements.


Quantum Descriptors for Predicting and Understanding the Structure-Activity Relationships of Michael Acceptor Warheads.
Predictive modeling and understanding of chemical warhead reactivities have the potential to accelerate targeted covalent drug discovery. Recently, the carbanion formation free energies as well as other ground-state electronic properties from density functional theory (DFT) calculations have been proposed as predictors of glutathione reactivities of Michael acceptors; however, no clear consensus exists. By profiling the thiol-Michael reactions of a diverse set of singly- and doubly-activated olefins, including several model warheads related to afatinib, here we reexamined the question of whether low-cost electronic properties can be used as predictors of reaction barriers. The electronic properties related to the carbanion intermediate were found to be strong predictors, e.g., the change in the Cβ charge accompanying carbanion formation. The least expensive reactant-only properties, the electrophilicity index, and the Cβ charge also show strong rank correlations, suggesting their utility as quantum descriptors. A second objective of the work is to clarify the effect of the β-dimethylaminomethyl (DMAM) substitution, which is incorporated in the warheads of several FDA-approved covalent drugs. Our data suggest that the β-DMAM substitution is cationic at neutral pH in solution and promotes acrylamide's intrinsic reactivity by enhancing the charge accumulation at Cα upon carbanion formation. In contrast, the inductive effect of the β-trimethylaminomethyl substitution is diminished due to steric hindrance. Together, these results reconcile the current views of the intrinsic reactivities of acrylamides and contribute to large-scale predictive modeling and an understanding of the structure-activity relationships of Michael acceptors for rational TCI design.


New antibiotic resistance genes associated with CTX-M plasmids from uropathogenic Nigerian Klebsiella pneumoniae.
To determine antibiotic resistance genes associated with 17 Nigerian CTX-M-positive Klebsiella pneumoniae plasmids from patients with community-acquired urinary tract infections. The size and restriction patterns of the plasmids were determined, and antibiotic resistance genes were identified using DNA-DNA hybridization, PCR assays, hybridization of PCR products with internal probes, and sequencing. All CTX-M plasmids were large (58-320 kb) and carried the following genes: aac(6')-Ib (aminoglycoside resistance) which included aac(6')-Ib-cr (aminoglycoside-fluoroquinolone resistance), aadA2 (aminoglycoside resistance), erm(B) (macrolide-lincosamide-streptogramin B resistance), blaTEM-1 (ampicillin resistance), tet(A) (tetracycline resistance), sul1 (sulphonamide resistance), dfr (trimethoprim resistance) and intI1, an integrase associated with class 1 integrons. Eleven (65%) plasmids carried an mph(A) gene (macrolide resistance), seven (41%) plasmids carried a qnrB1 gene (low-level quinolone resistance) and four (24%) plasmids carried multiple cat genes (chloramphenicol resistance). catA2, catA3 and qnrB1 genes and a 6 kb PstI fragment, carrying the blaCTX-M gene, were sequenced. This is the first description of catA2 and catA3 genes in Klebsiella spp. and the first description of the erm(B) and floR genes associated with a CTX-M plasmid. This is also the first report of qnrB1 and aac(6')-Ib-cr in isolates from Africa and the first report of these two genes on the same plasmid.


Viral hepatitis serological markers among pregnant women in Caracas, Venezuela: implication for perinatal transmission of hepatitis B and C.
Viral hepatitis serological markers were analyzed in two groups of pregnant women residing in Caracas from: 1) a maternity unit at the moment of delivery (106 sera, low income population), and 2) a private clinic during the third trimester of pregnancy (105 sera, medium-high economic class population). A higher percent positivity was observed in the maternity unit compared to the private clinic for hepatitis A virus (HAV) as measured by anti-HAV activity (96% vs 48%; p < 0.01%), for hepatitis B virus (HBV) as measured by anti-HBc activity (13% vs 2%; p < 0.01%), but not for HBV carriage, as measured by HBsAg (3.8% vs 0%; p = 0.06 %). These differences appear to correlate with the socio-economic level. All the HBsAg positive sera were HBeAg negative and negative for the presence of DNA by PCR, confirming the low rate of perinatal transmission observed in Venezuela. Two out of 106 sera (1.9%) were positive for HCV antibodies in the maternity unit and 0/105 in the private clinic, although these differences were non significant (N.S.). Two out of 106 sera (1.9%) were positive for HEV antibodies in the maternity unit and 1/80 (1.3%) in the private clinic (N.S.). The anti-HEV seropositivity probably reflects a past infection. The importance of testing these viral markers during pregnancy is discussed.


Prenatal diagnosis of chronic granulomatous disease.
A luminol enhanced chemiluminescence micromethod has been adapted for use in prenatal diagnosis of chronic granulomatous disease (CGD). After validation of the assay in normal adults, newborns, fetuses, CGD carriers, and CGD patients, the fetuses of two pregnant CGD carriers were tested after fetoscopic aspiration of fetal blood. Normal neutrophil chemiluminescence and nitroblue tetrazolium slide tests were followed by delivery of two healthy infants whose normality was confirmed. Amniocytes proved useless for the prenatal diagnosis of CGD. They were found to have negligible nitroblue tetrazolium reduction, oxygen metabolism, and oxygen dependence.


[The immunohistological study of developing human spinal cord--the localization of vimentine, GFAP in radial glial cell].
The morphological changes of radial glial cells in developing human spinal cord have been studied immunohistologically. The specimens extracted from developing human spinal cords, gestational age of 15 weeks, 30 weeks and 35 weeks, were prepared with cryostat for the investigation of anti vimentin mouse monoclonal antibody and of GFAP rabbit serum. We have stained the specimens for vimentin in accordance with ABC method, for GFAP in accordance with PAP method. On gestational age of 15 weeks, the fibers radially oriented from the central canal to pial surface were positive for vimentin and GFAP. Partially, early differentiated astrocytic cells were found. On gestational age of 30 weeks, radially oriented fibers were positive for vimentin and GFAP. They took more tortuous course, branching than those of 15 weeks. More differentiated astrocytic cells were found. On gestational age of 35 weeks, the staining for vimentin was very weak on radially oriented fibers and these fibers were more tortuous, branching than those of 30 weeks. More differentiated astrocytic cells than those of 30 weeks were found in rich amount. From results above, we concluded: 1) Radial glial cells in developing human spinal cord were positive for vimentin and GFAP. 2) The show weaker staining for vimentin in process of gestational age. 3) They differentiate to astrocyte. 4) They appear in earlier stage than suggested by previous reports.


Receptors for insulin and insulin-like growth factor-1 and insulin receptor substrate-1 mediate pathways that regulate islet function.
The insulin/insulin-like growth factor-1 (IGF-1) signalling pathways are present in most mammalian cells and play important roles in the growth and metabolism of tissues. Most proteins in these pathways have also been identified in the beta-cells of the pancreatic islets. Tissue-specific knockout of the insulin receptor (betaIRKO) or IGF-1 receptor (betaIGFRKO) in pancreatic beta-cells leads to altered glucose-sensing and glucose intolerance in adult mice, and betaIRKO mice show an age-dependent decrease in islet size and beta-cell mass. These data indicate that these receptors are important for differentiated function and are unlikely to play a major role in the early growth and/or development of the pancreatic islets. Conventional insulin receptor substrate-1 (IRS-1) knockouts manifest growth retardation and mild insulin resistance. The IRS-1 knockouts also display islet hyperplasia, defects in insulin secretory responses to multiple stimuli both in vivo and in vitro, reduced islet insulin content and an increased number of autophagic vacuoles in the beta-cells. Re-expression of IRS-1 in cultured beta-cells is able to partially restore the insulin content indicating that IRS-1 is involved in the regulation of insulin synthesis. Taken together, these data provide evidence that insulin and IGF-1 receptors and IRS-1, and potentially other proteins in the insulin/IGF-1 signalling pathway, contribute to the regulation of islet hormone secretion and synthesis and therefore in the maintenance of glucose homeostasis.


Structural evidence for asymmetrical nucleotide interactions in nitrogenase.
The roles of ATP hydrolysis in electron-transfer (ET) reactions of the nitrogenase catalytic cycle remain obscure. Here, we present a new structure of a nitrogenase complex crystallized with MgADP and MgAMPPCP, an ATP analogue. In this structure the two nucleotides are bound asymmetrically by the Fe-protein subunits connected to the two different MoFe-protein subunits. This binding mode suggests that ATP hydrolysis and phosphate release may proceed by a stepwise mechanism. Through the associated Fe-protein conformational changes, a stepwise mechanism is anticipated to prolong the lifetime of the Fe-protein-MoFe-protein complex and, in turn, could orchestrate the sequence of intracomplex ET required for substrate reduction.


Intron sequence directs RNA editing of the glutamate receptor subunit GluR2 coding sequence.
The Ca2+ permeability and the rectifying properties of the glutamate receptors assembled from the subunits GluR1-GluR4 depend upon a critical Arg in the GluR2 subunit located in a domain that has been proposed to span the membrane. The GluR2 subunit gene encodes a Gln (CAG) at this position, whereas the mRNA is edited so that it encodes an Arg (CGG) at this position [Sommer, B., Kohler, M., Sprengel, R. & Seeburg, P. H. (1991) Cell 67, 11-20]. The editing process is specific since only the GluR2 subunit RNA is edited even though the GluR1, GluR3, and GluR4 RNAs have a similar sequence. We show that this selective RNA editing depends upon a critical intron sequence in the GluR2 gene. This critical intron sequence is sufficient to cause editing of the GluR3 subunit exon in a chimera minigene constructed so that the GluR3 exon is placed upstream to the GluR2 intron sequence. Transfections of a neuronal cell line, N2a, with minigene constructs encoding different fragments of the GluR2 gene demonstrate that the 5' part of the 3' intron is essential for editing. Part of the exon and this critical intron sequence contains an inverted repeat that can fold into a structure consisting of three helical elements. Similar conclusions were reached by Higuchi, M., Single, F. n., Köhler, M., Sommer, B., Sprengel, R. & Seeburg, P. H. [(1993) Cell 75, 1361-1370]. These experiments demonstrate that the low Ca2+ permeability of the ionotropic non-N-methyl-D-aspartate glutamate receptors depends upon RNA editing, which requires a sequence in an intron 3' to the exon.


Benzyne 1,2,4-Trisubstitution and Dearomative 1,2,4-Trifunctionalization.
Both 1,2,4-trisubstitution and dearomative 1,2,4-trifunctionalization of benzyne have been accomplished from sulfoxides bearing a penta-2,4-dien-1-yl moiety. These cascade transformations proceed through a benzyne insertion into the S═O bond and an uncommon regiospecific anionic [4,5]-sigmatropic rearrangement, furnishing a C-O, C-S, and C-C bond on the C1-, C2-, and C4-position of a benzene ring, respectively. This study showcases new cascade benzyne reaction modes involving both distal C-H bond functionalization and dearomatization.


Three measures of tumor necrosis factor alpha activity and insulin resistance in nonobese Japanese type 2 diabetic patients.
The aim of the present study was to investigate the relationship between insulin resistance and tumor necrosis factor alpha (TNF-alpha) as well as soluble TNF receptors (sTNF-R), body mass index (BMI), leptin, adiponectin, and serum lipid profile including triglycerides in nonobese Japanese patients with type 2 diabetes. A total of 88 nonobese Japanese type 2 diabetic patients were studied. The duration of diabetes was 11.0 +/- 0.8 years. In conjunction with BMI, glycosylated hemoglobin (HbA1c), fasting concentrations of plasma glucose, serum lipids (triglycerides, high-density lipoprotein cholesterol, and total cholesterol), serum leptin, serum adiponectin, serum TNF-alpha, and soluble TNF receptors (sTNF-R1 and sTNF-R2) were also measured. Insulin resistance was estimated by the insulin resistance index of homeostasis model assessment. Insulin resistance was positively correlated with BMI, triglycerides, leptin, and total cholesterol and negatively correlated with adiponectin and high-density lipoprotein cholesterol. In contrast, insulin resistance was not associated with TNF-alpha, nor sTNF-R (sTNF-R1 and sTNF-R2) in our diabetic patients. There was no significant relationship between the 3 measures of TNF-alpha system (TNF-alpha, sTNF-R1, and sTNF-R2) and BMI, serum triglycerides, leptin, or adiponectin in these patients. From these results, it can be concluded that peripheral levels of TNF-alpha system activity are not a major factor responsible for insulin resistance in nonobese Japanese type 2 diabetic patients.


A simple mathematical model and practical approach for evaluating citric acid cycle fluxes in perfused rat hearts by 13C-NMR and 1H-NMR spectroscopy.
We propose a simple mathematical model and a practical approach for evaluating the flux constant and the absolute value of flux in the citric acid cycle in perfused organs by 13C-NMR and 1H-NMR spectroscopy. We demonstrate that 13C-NMR glutamate spectra are independent of the relative sizes of the mitochondrial and cytosolic compartments and the exchange rates of glutamates, unless there is a difference in 13C chemical shifts of glutamate carbons between the two compartments. Wistar rat hearts (five beating and four KCl-arrested hearts) were aerobically perfused with 100% enriched [2-(13)C]acetate and the kinetics of glutamate carbon labeling from perchloric acid extracts were studied at various perfusion times. Under our experimental conditions, the citric acid cycle flux constant, which represents the fraction of glutamate in exchange with the citric acid cycle per unit time, is about 0.350 +/- 0.003 min(-1) for beating hearts and 0.0741 +/- 0.004 min(-1) for KCl-arrested hearts. The absolute values of the citric acid flux for beating hearts and for KCl-arrested hearts are 1.06 +/- 0.06 micromol x min(-1) x mg(-1) and 0.21 +/- 0.02 micromol x min(-1) x g(-1), respectively. The fraction of unlabeled acetate determined from the proton signal of the methyl group is small and essentially the same in beating and arrested hearts (7.4 +/- 1.7% and 8.8 +/- 2.1%, respectively). Thus, the large difference in the Glu C2/C4 between beating and arrested hearts is not due to the important contribution from anaplerotic sources in arrested hearts but simply to a substantial difference in citric acid cycle fluxes. Our model fits the experimental data well, indicating a fast exchange between 2-oxoglutarate and glutamate in the mitochondria of rat hearts. Analysis of the flux constant, calculated from the half-time of glutamate C4 labeling given in the literature, allows for a comparison of the citric acid flux for various working conditions in different animal species.


The Silhouettes Fatigue Scale: comprehensibility and validity in older individuals.
Purpose: Fatigue has been shown to be one of the key factors that interfere in the quality of life of elderly individuals. In order to understand its impact and evaluate the efficacy of treatments that target fatigue, researchers and clinicians need psychometrically sound and easy to use assessment instruments. The aim of this work was to address this need by evaluating the comprehensibility and validity of the Silhouettes Fatigue Scale (SFS) in a sample of older individuals.Methods: A total of 70 older individuals participated in the study. Participants were interviewed individually and asked to rate their level of fatigue during the week before the interview using the SFS and the FACIT-Fatigue Scale (to help evaluate convergent validity), and respond to the Pain Catastrophizing Scale (to help evaluate discriminant validity).Results: The results indicate that the SFS is understandable and that the scores have an adequate convergent validity and discriminant validity when used with older adults.Conclusions: The SFS is a valid measure of fatigue that can be used with older adults. It fills the need for a brief and easy to administer and score measure, which can be used in situations where assessment burden is a significant issue.Implications for rehabilitationFatigue is a significant problem among the elderly resulting in significant disability, and psychometrically sound and easy to use questionnaires are needed.The Silhouettes Fatigue Scale (SFS) is a new single-item self-report fatigue rating scale.Results show that the SFS is understandable, and that the scores have discriminant and convergent validity when used with older adults.As it does not use written items, it may be more easily understood by people who have basic or even no literacy level, thus making it easier to use for a wider audience.


[Comparative study on differences of Paeonia lactiflora from different habitats based on fingerprint and chemometrics].
This study aims to compare the differences of Paeonia lactiflora from different habitats by establishing fingerprint. The fingerprint of P. lactiflora was established by UPLC. The samples collected from Sichuan,Hebei,Henan,Shanxi and Anhui were analyzed. The common peaks were identified by UPLC-Q-TOF/MS. The relative peak area of the common peaks was analyzed through similarity evaluation system( 2012 edition) for chromatographic fingerprint of traditional Chinese medicine developed by the National Pharmacopoeia Commission. Twelve common peaks were obtained and ten components were identified by reference substance and literature comparison. The similarity of each sample to the reference fingerprint is greater than 0. 900. However,all samples were clearly divided into 5 groups according to habitats after PLS-DA analysis. The peaks 2,6( ethyl gallate),10( galloypaeoniflorin) and 12( benzoyl paeoniflorin) were found to be the main difference components between the samples from five different habitats through the VIP value map. The study found that the variety of ingredients in the different areas are basically similar. But there are some differences in the content of the four components. The results of this study can provide reference at choosing and utilizing P. lactiflora from different places comprehensively.


Aerobic neuromuscular electrical stimulation--an emerging technology to improve haemoglobin A1c in type 2 diabetes mellitus: results of a pilot study.
A new generation of neuromuscular electrical stimulation (NMES) devices can exercise aerobically at equivalent rates to voluntary exercise. Many with type 2 diabetes cannot or will not exercise sufficiently. The objective of this pilot investigation was to see (1) if it was an acceptable training modality for men with type 2 diabetes mellitus and (2) to assess effects on haemoglobin A1c levels. A case series of eight men with type 2 diabetes mellitus (aged 53±8; body mass index 32±5 5 kg/m(2)) trained with the NMES system for 1 h 6 times weekly for 8 weeks, unsupervised, at home. There were no other medication or lifestyle interventions. The aerobic NMES exercise system delivers a repeating set of four complex staggered pulses at high intensities (typically 100 mA+) through an array of eight thigh electrodes. The primary outcome measures were changes in haemoglobin A1c and the responses in a questionnaire on participants' perceptions of the system. Body mass and composition were also measured before and after the NMES intervention period. All participants could use the system at a level that left them breathless and sweaty and with a heart rate over 120 beats per minute. Haemoglobin A1c levels improved by 0.8±0.7% from 7.4±1.3% (mean ± SD) to 6.6±1.0% (p=0.01). All participants considered the system suitable for people with diabetes, would recommend it and would continue to use it twice a week 'to maintain improvements'. These results suggest that aerobic NMES may be acceptable and have a beneficial effect on haemoglobin A1c of some men with diabetes. The treatment may be of particular benefit in those who will not or cannot do adequate amounts of voluntary exercise. A randomised control trial is required for conclusive efficacy data.


Multimode two-dimensional vibronic spectroscopy. I. Orientational response and polarization-selectivity.
Two-dimensional Electronic-Vibrational (2D EV) spectroscopy and two-dimensional Vibrational-Electronic (2D VE) spectroscopy are among the newest additions to the coherent multidimensional spectroscopy toolbox, and they are directly sensitive to vibronic couplings. In this first of two papers, the complete orientational response functions are developed for a model system consisting of two coupled anharmonic oscillators and two electronic states in order to simulate polarization-selective 2D EV and 2D VE spectra with arbitrary combinations of linearly polarized electric fields. Here, we propose analytical methods to isolate desired signals within complicated spectra and to extract the relative orientation between vibrational and vibronic dipole moments of the model system using combinations of polarization-selective 2D EV and 2D VE spectral features. Time-dependent peak amplitudes of coherence peaks are also discussed as means for isolating desired signals within the time-domain. This paper serves as a field guide for using polarization-selective 2D EV and 2D VE spectroscopies to map coupled vibronic coordinates on the molecular frame.


Van Buchem disease: lifetime evolution of radioclinical features.
The purpose of this study was to evaluate the lifetime evolution of the radioclinical features in a large family with van Buchem disease. The study population included 13 patients, ranging between 6 and 69 years. The evolution of the clinical features has been assessed by retrospective analysis of the clinical records of the patients. The age-related evolution of the cortical hyperostosis and defective modeling at the tubular bones was evaluated by morphometric analysis of hand films in 9 patients, compared with 9 control individuals. Progression of sclerosis of the craniofacial bones was evaluated by analysis of the skull radiographs of eleven van Buchem patients, taken at different age. Radioclinical features, including sclerosis of the cranial and tubular bones and cranial nerve deficit, become more prominent in older patients. Defective modeling of tubular bones, cortical thickness and medullary width progress with age. Radioclinical abnormalities of van Buchem patients become more prominent in older patients, which suggests that the van Buchem gene is very actively involved in bone metabolism throughout life. Morphometric analysis of the plain films supports the hypothesis that the physiological function of the van Buchem gene is to inhibit bone formation and possibly to regulate bone remodeling.


Synthesis and characterization of strontium-doped hydroxyapatite powder via sol-gel method.
Improvement of the mechanical properties of hydroxyapatite (HA) can be achieved by the incorporation of metal. In addition, incorporation of strontium ion into HA crystal structures has been proved effective to enhance biochemical properties of bone implant. In this research, strontium-doped HA powder was developed via a sol-gel method to produce extraordinarily fine strontium-doped HA (Sr-doped HA) powder. XRD measurement had shown that the powder contained hydroxyapatite phase only for all doping concentration except for 2%, showing that Sr atoms have suppressed the appearance of beta-TCP as the secondary phase. Morphological evaluation by FESEM measurement shows that the particles of the Sr-doped HA agglomerates are globular in shape with an average size of 1-2 microm in diameter while the primary particles have a diameter of 30-150 nm in average.


Identification of NR5A1 (SF-1/AD4BP) gene expression modulators by large-scale gain and loss of function studies.
Nuclear receptor subfamily 5, group A, member 1 (NR5A1 previously known as SF-1/AD4BP) is a transcription factor involved in the development of adrenal/gonadal tissues and steroidogenic lineage cell differentiation in adult somatic stem cells. To understand the cellular signaling network that regulates NR5A1 gene expression, loss of function screening with an siRNA kinome library, and gain of function screening with an addressable full-length cDNA library representing one quarter of the human genome was carried out. The NR5A1 gene expression was activated in mesenchymal stem cells by siRNA directed against protein kinase C (PKC)-delta, erb-B3, RhoGAP (ARHGAP26), and hexokinase 2, none of which were previously known to be involved in the NR5A1 gene expression. Among these, we identified crosstalk between erb-B3 and PKC-delta signaling cascades. In addition, the gain of function studies indicated that sex-determining region Y (SRY)-box 15 (SOX15), TEA domain family member 4, KIAA1257 (a gene of unknown function), ADAM metallopeptidase with thrombospondin type 1 motif 6, Josephin domain containing 1, centromere protein, TATA box-binding protein-associated factor 5-like RNA polymerase, and inducible T-cell co-stimulator activate NR5A1 gene expression. These results provide new insights into the molecular mechanisms of NR5A1 gene expression.


A perspective on the early management of abdominal trauma.
Blunt trauma in Australia is most commonly due to road accidents and is often multisystem in its effect on the body. Whereas some cases of intra-abdominal injury result in massive bleeding, and may be readily diagnosed clinically, many abdominal injuries are difficult to diagnose on initial clinical examination. Delays in treatment can result in otherwise avoidable morbidity and mortality, and the practice of diagnosis by repeated clinical examination over long periods of time is to be condemned in principle. All abdominal injuries can (and should) now be diagnosed and treatment commenced within 2-4 h of admission to hospital. Diagnostic peritoneal lavage (DPL) is the most sensitive indicator of intraperitoneal blood after trauma, and if employed early, and interpreted with a low threshold for positivity, early treatment of all intraperitoneal organ disruption can be undertaken. The best organ-imaging technique available for abdominal trauma is computerized tomography (CT) scan, but it is not as sensitive as DPL in the diagnosis of haemoperitoneum, and its accuracy in defining bowel injury is not proved. Several factors dictate the choice of DPL or CT scan in difficult trauma cases, and these include the stability of the patient, the availability of CT scan, the experience of the treating physician with either modality, the organs most at risk of injury in any case, and the decision to attempt conservative or operative management. In a small number of cases, doubt may still exist after CT and/or DPL, and an early laparotomy remains the 'gold standard' of diagnosis in such situations. In penetrating trauma, laparotomy is indicated if wound exploration shows penetration of the peritoneum.


Broadband wavelength-swept Cr4+:YAG crystal fiber laser.
We present a broadband wavelength-swept laser using a 16-µm-core-diameter Cr4+:YAG crystal fiber as the gain medium. The laser-diode-pumped crystal fiber laser has a threshold of only 102 mW due to the low propagation loss and high heat dissipation efficiency. The laser achieves a sweeping wavelength range of 134 nm, centered around 1425 nm, with a scanning speed of 163 k nm/s. Notably, the cross-polarization-coupled excited state absorption of the signal wavelength constrained the long-wavelength lasing limit. This laser has the potential for swept source optical coherence tomography applications, providing an axial resolution of 11.4 µm.


Ehlers-Danlos syndrome.
We present a clinical case of a 63-year old Caucasian man with Ehlers-Danlos syndrome who was admitted with atrial fibrillation and arterial hypertension. We present this not as a cardiological case but instead address the key questions of differential diagnosis, diagnosis criteria, management and improving the patient's quality of life.


Binding of basic fibroblast growth factor to normal and neovascularized rabbit cornea.
The labeling pattern of frozen sections of rabbit cornea incubated with radioiodinated basic fibroblast growth factor (bFGF) was investigated in normal corneas and prostaglandin-induced neovascularized corneas by autoradiography followed by image analysis. 125I-bFGF binds to Bowman's, Descemet's, and vascular basement membranes in a dose-dependent manner. The specificity of the binding of bFGF to basement membrane was demonstrated by the following experiments: 1) an excess of unlabeled growth factor displaced the labeling; 2) histones did not modify the labeling; and 3) 2 M NaCl washing and enzymatic treatment with heparitinase prevented binding of labeled growth factor without apparent destruction of the overall structure of the basement membrane. Our results suggest that bFGF binds to the heparan sulfate proteoglycan of basement membranes. Both normal limbal vessels and the newly formed corneal vessels exhibited the same type of labeling but with different intensities, according to the degree of maturation of the new vessels. bFGF binding also is located clearly on the endothelial cells in both types of vessels. This second binding site could correspond to the high affinity receptors on the cell surface and suggests a direct interaction of bFGF with endothelial cells during new vessel formation.


Facilitators and barriers to adherence to gluten-free diet among adults with celiac disease: a systematic review.
Coeliac disease (CD) is a chronic, autoimmune disease that prevents individuals from processing gluten, leading to adverse health effects. People with CD should adhere to a gluten-free diet (GFD); however, adherence rates are well below optimal in adults with CD, ranging between 42% and 91%. To date, limited evidence is available on the nature and magnitude of factors that affect adherence to GFD. The present study aimed to develop a systematic review that critically appraises and synthesises evidence on facilitators and barriers that affect adherence to GFD among adults with CD. Four databases were searched (Ovid Medline, CINAHL, PsychInfo and Embase) using variant keywords to identify empirical studies meeting the inclusion/exclusion criteria. A coding scheme was developed to extract relevant information from each article. Forty articles were included. Grounded in the bioecological theory of development, we synthesised the facilitators and barriers in the literature into a social ecological model with multiple levels: system, community, organisational, interpersonal and individual. The studies varied by design and level of evidence; only one randomised trial was identified. The most significant facilitators include (% of studies): increased education (22.5%); increased knowledge of a GFD (20%); increased intention/self-regulatory efficacy (17.5%); and coeliac association membership (12.5%). The most significant barriers include: lower knowledge of CD (35%); restaurant/supermarket shopping (30%); poor patient education from practitioner (17.5%); and low intention/motivation to adhere to a GFD (17.5%). Improving knowledge of a GFD, becoming a member of a coeliac association, and improving practitioners' abilities to educate patients on CD will create opportunities for improved adherence to GFD among adults with CD.


Advances in turbulent mixing techniques to study microsecond protein folding reactions.
Recent experimental and computational advances in the protein folding arena have shown that the readout of the one-dimensional sequence information into three-dimensional structure begins within the first few microseconds of folding. The initiation of refolding reactions has been achieved by several means, including temperature jumps, flash photolysis, pressure jumps, and rapid mixing methods. One of the most commonly used means of initiating refolding of chemically denatured proteins is by turbulent flow mixing with refolding dilution buffer, where greater than 99% mixing efficiency has been achieved within 10's of microseconds. Successful interfacing of turbulent flow mixers with complementary detection methods, including time-resolved Fluorescence Spectroscopy (trFL), Förster Resonance Energy Transfer, Circular Dichroism, Small-Angle X-ray Scattering, Hydrogen Exchange followed by Mass Spectrometry and Nuclear Magnetic Resonance Spectroscopy, Infrared Spectroscopy (IR), and Fourier Transform IR Spectroscopy, has made this technique very attractive for monitoring various aspects of structure formation during folding. Although continuous-flow (CF) mixing devices interfaced with trFL detection have a dead time of only 30 µs, burst phases have been detected in this time scale during folding of peptides and of large proteins (e.g., CheY and TIM barrels). Furthermore, a major limitation of the CF mixing technique has been the requirement of large quantities of sample. In this brief communication, we will discuss the recent flurry of activity in micromachining and microfluidics, guided by computational simulations, which are likely to lead to dramatic improvements in time resolution and sample consumption for CF mixers over the next few years.


First contact: Fine structure of the impact flash and ejecta during hypervelocity impact.
Hypervelocity impacts are a significant threat in low-earth orbit and in hypersonic flight applications. The earliest observable phenomena and mechanisms activated under these extreme conditions are typically obscured by a very bright flash, called the impact flash, that contains the signatures of the critical mechanisms, the impacting materials, and the impact environment. However, these signatures have been very difficult to observe because of the small length and time scales involved coupled with the high intensities associated with the flash. Here we perform experiments investigating the structure and characteristics of the impact flash generated by 3 km s-1 spherical projectile impacts on structural metals using temporally co-registered high-resolution diagnostics. Reciprocal impact configurations, in which the projectile and target material are swapped, are used to demonstrate the coupling of early-stage mechanisms in the flash and later-stage ejection mechanisms responsible for the development of the impact crater.


Treatment of Buerger's disease with electrical spinal cord stimulation--review of three cases.
Buerger's disease or obliterating thromboangiitis is an inflammatory pathologic condition affecting the distal vascular segments; it strikes young adults, especially males and heavy smokers. Medical and surgical treatment often fail to heal these patients, especially considering the frequent relapse of this disease linked with tobacco abuse--definitive healing often involves limb amputation. Electrical spinal cord stimulation is evaluated in this study with an analgesic aim and for improvement in skin microcirculation, with the goal of long-term healing of diseased limbs.


Quantifying the intrinsic effects of two point mutation models of proline-proline diamino acid diamide: a first-principle computational study.
Two sites of a Pro-Pro diamide were subjected to individual Pro --> Thr point mutations. The parent diamide Pro-Pro as well as selected conformers of the Pro-Thr and Thr-Pro mutant models were subjected to molecular computations at the B3LYP/6-31G(d) level of theory. At the optimized geometries, thermodynamic functions (S, H, and G) were computed. In order to assess relative stabilities of the mutant models, isodesmic reactions were constructed to calculate DeltaS, DeltaH, and DeltaG, relative to the initial Pro-Pro state. The importance of intramolecular hydrogen bonds, involving the -OH group of the Thr side chain, which emerged after the point mutations were also examined. Our findings suggest a novel approach to analyzing the stability of point mutants in peptide models through the analysis of thermodynamic functions.


Strong, but Wrong: Lay People's and Police Officers' Beliefs about Verbal and Nonverbal Cues to Deception.
The present study investigated the beliefs of students and police officers about cues to deception. A total of 95 police officers and 104 undergraduate students filled out a questionnaire addressing beliefs about cues to deception. Twenty-eight verbal cues were included in the questionnaire, all extracted from verbal credibility assessment tools (i.e., CBCA, RM, and SCAN). We investigated to what extent beliefs about nonverbal and verbal cues of deception differed between lay people (students) and police officers, and whether these beliefs were in agreement with objective cues known from research. Both students and police officers believed the usual stereotypical, but non-diagnostic (nonverbal) cues such as gaze aversion and increased movement to be indicative of deception. Yet, participants were less inclined to overestimate the relationship between verbal cues and deception and their beliefs fitted better with what we know from research. The implications of these findings for practice are discussed.


Potential asbestos exposure among patients with primary lung cancer in Japan.
To investigate the extent of asbestos exposure among patients with primary lung cancer in Japan. A retrospective estimation of potential asbestos-exposed individuals, as determined by the presence of pleural plaques identified on chest computed tomography (CT), was conducted on 885 pathologically confirmed primary lung cancer patients (mean age 71.3 years, 641 males). All patients were diagnosed at 29 hospitals across Japan between 2006 and 2007. Since these hospitals belong to the Japan Federation of Democratic Medical Institutions (MIN-IREN), an organization of medical institutions for workers, the study subjects may contain a higher proportion of workers than the general population. Pleural plaques were identified in 12.8% of subjects (15.8% in males and 4.9% in females), consisting exclusively of cases older than 50 years. They were found most frequently on the chest wall pleura (96.5%), followed by the diaphragm (23.9%) and mediastinum (9.7%). Calcifications were seen in 47 cases (41.6%). The highest prevalence of pleural plaques was seen among workers from construction-related fields (37.7%). No distinct lung cancer histology was observed in patients with pleural plaques. Coexistence of pleural plaques and small irregular opacities was observed in 2.5% of subjects. In a Japanese population representing more workers than general Japanese, 12.8% of patients with primary lung cancer may have experienced asbestos exposure at some time in the past. Special medical attention should be paid to individuals with a history of employment in construction-related occupations, as workers in this sector showed the highest prevalence of pleural plaques.


On the influence of extracellular fluid volume expansion on bicarbonate reabsorption in the rat.
Bicarbonate reabsorption is classically regarded as a rate-limited process characterized by saturation kinetics. The tubular maximum (Tm), however, varies with glomerular filtration rate. Thus bicarbonate reabsorption, in common with sodium reabsorption, is characterized by glomerulo-tubular balance. The examination of bicarbonate reabsorption is accomplished using the bicarbonate titration technique; however, this method in its traditional form leads to marked expansion of extracellular fluid (ECF) volume. The possibility exists, therefore, that glomerulo-tubular balance for bicarbonate is altered by the volume expansion and thus that the classic pattern of reabsorption may actually reflect inhibited bicarbonate reabsorptive capacity. The present studies were performed in rats to examine this possibility. Bicarbonate titration studies were performed in two groups of animals: (a) those in which ECF volume expansion was minimized; and (b) those in which ECF volume expansion was exaggerated. In the first group, no Tm for bicarbonate was observed either in the majority of individual rats studied or in a group plot for all rats studied despite the fact that plasma bicarbonate concentrations were increased to values in excess of 60 mEq/liter. In the second group, a clear Tm was demonstrated both in individual animals and in group data and there was a lowered threshold for the excretion of bicarbonate. The data thus lend support to the view that the "normal" Tm for bicarbonate may actually represent an inhibited level of bicarbonate reabsorption induced by ECF volume expansion.


Etiology and Antimicrobial Susceptibility Pattern of Pathogenic Bacteria in Children Subjected to UTI: A Referral Hospital-Based Study in Northwest of Iran.
Urinary tract infection (UTI) is 1 of the most common bacterial diseases in children with a considerable resistance to antimicrobials. This 5 years prospective study was carried out to determine the frequency of isolation and antimicrobial resistance patterns of uropathogens among children subjected to urine culture at Tabriz Children Educational-Health Care Center, in the northwest of Iran. Organisms were isolated using standard culture techniques. Frequency of UTI among children examined by urine culture was 3.6%. The isolated bacteria were Escherichia coli (71.4%), followed by Klebsiella spp. (9.6%), Enterococcus spp. (6.4%), Pseudomonas aeruginosa (4.2%), Serratia spp. (4.2%), and Enterobacter spp. (4.2%). E coli resistance levels were 11% for nitrofurantoin, 15% for ciprofloxacin, 25% for nalidixic acid, and 30% to 75% for amikacin, gentamicin, ceftriaxone, ceftizoxime, cefotaxime, and co-trimoxazole. Among the tested antibiotics, ciprofloxacin, showed the highest activity (100%) against Klebsiella and P aeruginosa isolates followed by amikacin, nalidixic acid, and gentamicin. Overall, the highly active antibiotic against Gram-negative and Gram-positive organisms was amikacin and then ciprofloxacin. On the other hand, the empirical initial therapy with co-trimoxazole and third-generation cephalosporins would be inadequate for more cases of UTI in the study area. Moreover, susceptibility testing should be carried out on all clinical isolates, and the empirical antibiotic treatment changed accordingly.


Magnetization transfer imaging of the pituitary gland.
Magnetization transfer (MT) techniques provide tissue contrast which depends mainly on the concentration of macromolecules. The magnetization transfer phenomenon is determined by the restricted macromolecular protons and is quantified by the magnetization transfer ratio (MTR). Since many macromolecular structures are implicated in the secretory activity of the pituitary gland, this imaging technique has recently been used for the study of the normal adenohypophysis and the pre-operative and post-operative evaluation of pituitary adenomas. Significant changes of the MTR with age occur in normal subjects. In patients with hyperprolactinemia, the MTR of prolactin-secreting tumors is higher and that of the non secreting adenomas is lower compared to the MTR values of the normal pituitary gland of age and sex matched controls. In some patients operated on for growth hormone adenomas, although classic MR images were negative for residual tumor, increased MTR values were highly suggestive of persistence of adenoma tissue, in agreement with biochemical findings of persisting secretory activity. These data suggest that MT techniques might be an additional useful tool in the assessment of pituitary gland disorders.


[A psychodynamic approach in counselling vulnerable persons for Chorea Huntington -- a case report].
The availability of predictive testing for neurodegenerative diseases such as Chorea Huntington has far-reaching consequences on psychological, ethical, and legal issues. The special situation of persons vulnerable for the disease requires a comprehensive counselling including psychotherapeutic measures. On the basis of a case report, the authors outline a psychodynamic practice, which intends not only the identification of deliberate arguments and development of coping strategies, but also a clarification of unconscious backgrounds and expectations. In the discussion, the necessity of sufficient time is stressed that allows the reflection of repressed motives in respect of the genetic testing.


Tissue engineering with peripheral blood-derived mesenchymal stem cells promotes the regeneration of injured peripheral nerves.
Peripheral nerve injury repair can be enhanced by Schwann cell (SC) transplantation, but clinical applications are limited by the lack of a cell source. Thus, alternative systems for generating SCs are desired. Herein, we found the peripheral blood-derived mesenchymal stem cells (PBMSCs) could be induced into SC like cells with expressing SC-specific markers (S100, P75NTR and CNPase) and functional factors (NGF, NT-3, c-Fos, and Krox20). When the induced PBMSCs (iPBMSCs) were transplanted into crushed rat sciatic nerves, they functioned as SCs by wrapping the injured axons and expressing myelin specific marker of MBP. Furthermore, iPBMSCs seeded in an artificial nerve conduit to bridge a 10-mm defect in a sciatic nerve achieved significant nerve regeneration outcomes, including axonal regeneration and remyelination, nerve conduction recovery, and restoration of motor function, and attenuated myoatrophy and neuromuscular junction degeneration in the target muscle. Overall, the data from this study indicated that PBMSCs can transdifferentiate towards SC-like cells and have potential as grafting cells for nerve tissue engineering.


Predictive Value of Neutrophil Lymphocyte Ratio and Platelet Lymphocyte Ratio in Patients with Coronary Slow Flow.
Increased microvascular resistance due to chronic inflammation is assumed to be one of the mechanisms associated with coronary slow flow (CSF). Previous studies have shown that the platelet-to-lymphocyte ratio (PLR) and the neutrophil-lymphocyte ratio (NLR) are markers of inflammation for various diseases. In this study we aimed to evaluate the relationship between CSF and PLR-NLR. Seventy-eight patients with CSF and 50 patients with normal coronary flow were enrolled into this study. The study subjects underwent medical examination and testing, after which their platelet-to-lymphocyte ratios and NLR values were calculated. An independent observer measured the coronary flow rate by Thrombolysis in Myocardial Infarction Frame Count (TFC) method. The platelet-to-lymphocyte ratio and NLR values were compared between the groups and correlation analysis was performed to explore the relationship between mean TFC with PLR and NLR. Platelet-to-lymphocyte ratio and NLR values were significantly higher in patients with CSF (p < 0.001). There was a positive significant correlation between TFC with NLR and PLR (Spearman's Rho: 0.59, p < 0.001 and Spearman's Rho: 0.30, p = 0.001, respectively). Multivariate logistic regression analysis revealed that NLR is the one independent predictor for CSF. This study demonstrated an association between CSF and PLR-NLR. Although the exact mechanism could not be explained, our findings support the possible role of inflammation in CSF physiopathology.


Macronutrient Digestion and Absorption in the Preterm Infant.
The human fetus receives oral nutrition through swallowed amniotic fluid and this makes a significant nutritional contribution to the fetus. Postnatally, macronutrient absorption and digestion appear to function well in the preterm infant. Although pancreatic function is relatively poor, the newborn infant has several mechanisms to overcome this. These include a range of digestive enzymes in human milk, novel digestive enzymes involved in fat and protein digestion that do not appear to be present in the older child or adult, and the presence of a Bifidobacterium-rich colonic microbiome that may "scavenge" unabsorbed macronutrients and make them available to the infant.


[Vitamin-mineral supplements in nutrition of adults].
The diet of population consisting of natural products is quite adequate and even excessive of energy consumption, but is not able to meet fully the need of organism in a number of micronutrients. Due to lack of sun exposure and long presence indoors endogenous synthesis of vitamin D in the skin by ultraviolet radiation does not provide the body's need for this vitamin. Intake of vitaminmineral supplements (VMS) is appropriate because combined deficiency of vitamins and minerals takes place in population. Prophylactic doses (equal to physiological needs) provide a diet completeness and reduce the risk of vitamin deficiency and its consequences. The high incidence of combined deficiency of vitamins among population and the existence of vitamin interactions are the basis for the application of the multivitamins. The simultaneous intake of vitamins is more physiological, their combination is more effective than a separate or isolated destination of each of them. Efficacy of the VMS has been shown in the treatment and prevention of some diseases. The main requirements for the VMS are full list of vitamins and minerals, the lack of which is detected most frequently, in doses covering the needs of organism. For the health of the pregnant woman and her unborn child preference should be given for complexes, containing DHA and/or probiotics along with vitamins. The principles of the selection of the composition and vitamin doses in the VMS for using patients suffering from various pathologies should be based on data on the patient's sufficiency with vitamins, the understanding of the role of vitamin deficiency in the pathogenesis of the disease, as well as on the composition of the diet and its modifications.


Elucidating the effect of copper as a redox additive and dopant on the performance of a PANI based supercapacitor.
In this article, the effect of copper (Cu) as a redox additive and dopant on the performance of a polyaniline (PANI) based supercapacitor was thoroughly investigated. The electrochemical properties of PANI in H2SO4 and in H2SO4 + CuSO4 and Cu doped PANI in H2SO4 were studied using cyclic voltammetry (CV) and impedance spectroscopy (IS). The CV result indicates that the capacity of PANI in H2SO4 was significantly improved with the introduction of Cu(2+) ions into the electrolyte, but it appeared unstable because of underpotential deposition of copper over the PANI surface and the relatively irreversible nature of the redox reaction. However, a stable and improved performance was obtained for Cu doped PANI due to the combined effect of an increase in conductivity and the surface modification of the PANI film. For Cu doped PANI, nearly ∼2.4 and ∼1.5 fold improved interfacial capacitance was achieved compared to that of PANI (H2SO4) and PANI (H2SO4 + CuSO4) respectively. The obtained Nyquist spectra for all the configurations were analysed using an equivalent circuit to understand the fundamentals of capacitive and resistive response of the supercapacitor. The IS measurements lead to direct determination of parameters like series resistance, rate capability of electrodes, ion diffusion phenomena and interfacial capacitance. The experimental results and their analysis will have significant impact on understanding the effect of dopants and redox additives on the performance of PANI based supercapacitors and also lay the basis for designing a supercapacitor with an appropriate electrode and electrolyte material for numerous industrial and consumer applications.


A review of the shortened dental arch concept focusing on the work by the Käyser/Nijmegen group.
The aims of this paper were to review the literature on shortened dental arches with special focus on publications of the Käyser/Nijmegen group, and to evaluate the discussions on the shortened dental arch concept found in the literature. A MEDLINE (PubMed) search was conducted for articles in English published in the dental literature from 1966 to November 2005. The search revealed epidemiological, cross-sectional and longitudinal clinical studies as well as opinion papers, the majority of which were published by the Dutch group. The studies found in general no clinically significant differences between subjects with shortened dental arches of three to five occlusal units and complete dental arches regarding variables such as masticatory ability, signs and symptoms of temporomandibular disorders, migration of remaining teeth, periodontal support, and oral comfort. The findings from cross-sectional studies were corroborated longitudinally. No systematic clinical study with conflicting results was found. The shortened dental arch concept was accepted by a great majority of dentists but not widely practised. The studies reviewed showed that shortened dental arches comprising anterior and premolar teeth in general fulfil the requirements of a functional dentition. It may therefore be concluded that the concept deserves serious consideration in treatment planning for partially edentulous patients. However, with ongoing changes, e.g. in dental health and economy, the concept requires continuing research, evaluation and discussion. Patients' needs and demands vary much and should be individually assessed but the shortened dental arch concept deserves to be included in all treatment planning for partially edentulous patients.


Development and evaluation of a venous computed tomography radiomics model to predict lymph node metastasis from non-small cell lung cancer.
The objective of this study was to develop a venous computed tomography (CT)-based radiomics model to predict the lymph node metastasis (LNM) in patients with non-small cell lung cancer (NSCLC). A total of 411 consecutive patients with NSCLC underwent tumor resection and lymph node (LN) dissection from January 2018 to September 2018 in our hospital. A radiologist with 20 years of diagnostic experience retrospectively reviewed all CT scans and classified all visible LNs into LNM and non-LNM groups without the knowledge of pathological diagnosis. A logistic regression model (radiomics model) in classification of pathology-confirmed NSCLC patients with and without LNM was developed on radiomics features for NSCLC patients. A morphology model was also developed on qualitative morphology features in venous CT scans. A training group included 288 patients (99 with and 189 without LNM) and a validation group included 123 patients (42 and 81, respectively). The receiver operating characteristic curve was performed to discriminate LNM (+) from LNM (-) for CT-reported status, the morphology model and the radiomics model. The area under the curve value in LNM classification on the training group was significantly greater at 0.79 (95% confidence interval [CI]: 0.77-0.81) by use of the radiomics model (build by best 10 features in predicting LNM) compared with 0.51 by CT-reported LN status (P < .001) or 0.66 (95% CI: 0.64-0.68) by morphology model (build by tumor size and spiculation) (P < .001). Similarly, the area under the curve value on the validation group was 0.73 (95% CI: 0.70-0.76) by the radiomics model, compared with 0.52 or 0.63 (95% CI: 0.60-0.66) by the other 2 (both P < .001). A radiomics model shows excellent performance for predicting LNM in NSCLC patients. This predictive radiomics model may benefit patients to get better treatments such as an appropriate surgery.


Origin of urea-soluble protein in the selenite cataract. Role of beta-crystallin proteolysis and calpain II.
Nuclear cataract resulting from an overdose of selenite was characterized by a five-fold increase in nuclear urea-soluble protein. The origin of this urea-soluble protein was examined by two-dimensional electrophoresis, immunoblotting with monospecific antisera against rat lens crystallins, and tryptic mapping. Cataractous urea-soluble protein was primarily composed of insolubilized beta- and gamma-crystallin polypeptides. Polypeptides from cataractous urea-soluble protein, and normal beta L-crystallin aggregates were compared by tryptic mapping. Approximately 19% of the urea-soluble protein from opaque nuclei was composed of 24.7 and 24.0 K polypeptides derived by limited proteolysis of 26.5 K beta L-crystallin polypeptide. Incubation of 26.5 K beta-crystallin polypeptide with purified rat lens calpain II in vitro caused production of fragments with similar molecular weights to polypeptides found in cataractous lenses. These results support the hypothesis that proteolysis may contribute to formation of urea-soluble protein in selenite cataract.


Diagnostic difficulties in myasthenia gravis.
Four patients with myasthenia gravis presented with severe, largely isolated, bulbar and respiratory muscles weakness. Tensilon tests were positive and antiacetylcholine receptor (anti-AChR) antibody titers were negative in all patients. Only 1 patient had a greater than 10% decremental response during the period of respiratory failure. Although routine nerve conduction studies were normal, all had very low-amplitude diaphragmatic compound muscle action potentials. Three patients had abundant fibrillation potentials and positive sharp waves largely restricted to respiratory muscles. Clinical and electrophysiological findings improved with corticosteroids, and surprisingly, decremental responses became positive in all patients. The assessment of patients with largely isolated bulbar and respiratory muscle weakness due to myasthenia gravis may be difficult and misleading, as anti-AChR antibody titers may be negative, decremental responses may be absent, and electrophysiological assessment atypical. Due consideration of clinical symptomatology, a Tensilon test, and a trial of immunosuppression may be necessary to establish the diagnosis.


Sonographic demonstration of hepatic venous gas in mesenteric arterial thrombosis.
Hepatic portal venous gas is an ominous prognostic sign in bowel necrosis from mesenteric arterial occlusion. Ultrasonic examination is a sensitive and accurate method of demonstrating portal venous gas. We describe a case where the ultrasonic diagnosis of portal venous gas led to the rapid diagnosis of bowel infarction. Ultrasound is an appropriate emergency examination in all patients with suspected mesenteric artery occlusion.


The phylogeny of Mediterranean tortoises and their close relatives based on complete mitochondrial genome sequences from museum specimens.
As part of an ongoing project to generate a mitochondrial database for terrestrial tortoises based on museum specimens, the complete mitochondrial genome sequences of 10 species and a approximately 14kb sequence from an eleventh species are reported. The sampling of the present study emphasizes Mediterranean tortoises (genus Testudo and their close relatives). Our new sequences are aligned, along with those of two testudinoid turtles from GenBank, Chrysemys picta and Mauremys reevesii, yielding an alignment of 14,858 positions, of which 3238 are parsimony informative. We develop a phylogenetic taxonomy for Testudo and related species based on well-supported, diagnosable clades. Several well-supported nodes are recovered, including the monophyly of a restricted Testudo, T. kleinmanni+T. marginata (the Chersus clade), and the placement of the enigmatic African pancake tortoise (Malacochersus tornieri) within the predominantly Palearctic greater Testudo group (Testudona tax. nov.). Despite the large amount of sequence reported, there is low statistical support for some nodes within Testudona and so we do not propose names for those groups. A preliminary and conservative estimation of divergence times implies a late Miocene diversification for the testudonan clade (6-10 million years ago), matching their first appearance in the fossil record. The multi-continental distribution of testudonan turtles can be explained by the establishment of permanent connections between Europe, Africa, and Asia at this time. The arrival of testudonan turtles to Africa occurred after one or more initial tortoise invasions gave rise to the diverse (>25 species) 'Geochelone complex.' Two unusual genomic features are reported for the mtDNA of one tortoise, M. tornieri: (1) nad4 has a shift of reading frame that we suggest is resolved by translational frameshifting of the mRNA on the ribosome during protein synthesis and (2) there are two copies of the control region and trnF, with the latter having experienced multiple-nucleotide substitutions in a pattern suggesting that each is being maintained by selection.


Whole body 16-row multislice CT in emergency room: effects of different protocols on scanning time, image quality and radiation exposure.
The objective of this study was to compare two different scanning protocols in patients suspected to have multiple trauma using multidetector 16-row computed tomography (CT) to better define scanning time, imaging quality and radiation exposure. Forty-six patients, between March 2004 and March 2005, with suspected multiple trauma (cerebral, spine, chest, abdominal and pelvis) were evaluated with two different protocols: Protocol "A" 26 patients; Protocol "B" 20 patients. Protocol A consists of a single-pass continuous whole-body acquisition (from vertex to pubic symphysis), whereas Protocol B of conventional segmented acquisition with scanning of body segments individually. Both protocols were performed using a multidetector 16-rows CT (Light-Speed 16, General Electric Medical System, Milwaukee, WI, USA) with the same technical factors. Radiation dose was evaluated in two ways: computer tomography dose index (CTDI) = dose measured in central and peripheral region of the subjects as a direct result of a CT section acquisition of T millimeters thick (independent from the two protocols) and dose length product (DLP) = total dose deposited over the length of the acquisition (dependent from the two protocols). Image quality was rated according to the following scores: 1, excellent; 2, good; 3, satisfactory; 4, moderate and 5, poor. The results were compared using Wilcoxon's test to identify significant difference in terms of image quality, scanning time, radiation exposure and presence of artifacts, assuming significance at a p value of <0.05. In the single-pass scanning, DLP was 2.671 mGy x cm and a total scan time of 35 s. In whole-body protocols, we have seen artifacts due to arm adduction in thorax and less image quality in brain. In the conventional segmented study, DLP was 3.217 mGy x cm and a total scan time of 65 s; this protocol offered less extraction capabilities of off-axial on focused images of the entire spine, aorta, facial bones or hip without rescanning. Protocol A revealed a significant decrease in scan time (35 vs 65 min, p < 0.05), time in the CT examination room (21.7 vs 31.6 min.; p < 0.05), and final image analysis (83.7 vs 102.9 min; p < 0.05) and radiation dose compared to protocol B (p < 0.05). No significant difference was found for patient transport time, image reconstruction time and imaging quality. Reconstruction and isotropic reformation of axial image acquired by whole-body, single-pass protocols due to entire spine evaluation, aortic and splanchnic CT angiography eliminate additional studies. The whole-body, single-pass protocols, compared with segmented acquisitions protocols, resulted in a reduced total radiation dose without relevant loss of diagnostic image information.


Subjective sleep complaints in pediatric depression: a controlled study and comparison with EEG measures of sleep and waking.
Children with major depressive disorder (MDD) often complain of sleep disturbances; however, polysomnographic studies have failed to find objective evidence of these disturbances. This article examines subjective sleep reports of children with MDD and healthy controls focusing on comparing subjective and objective sleep measures. Fifty-one subjects with MDD and 42 healthy subjects, 8-17 years old, participated in a comprehensive psychobiologic study including three nights of EEG sleep recording. Each morning, subjects completed a post-sleep form subjectively rating their sleep, which was then compared with their polysomnographic studies. Depressed subjects reported significantly worse sleep on four scales: subjective sleep quality, perceived number of awakenings, estimated minutes awake, and perceived ease of waking. In contrast to these subjective complaints, objective EEG measures indicated no evidence of disturbed sleep in the depressed sample compared to controls. Furthermore, exploratory analyses focusing on the subset of depressed subjects with the greatest subjective sleep disturbance showed, paradoxically, significantly better sleep in terms of the number of EEG awakenings and objective disturbances. Despite clinical evidence of subjective sleep complaints in depressed children, our EEG measures showed little evidence to indicate an objective basis for these perceptions. These findings raise provocative questions regarding the nature of sleep complaints associated with early-onset depression.


[The effect of ionotropic glutamate receptor antagonist on pentylenetetrazole-indused seizures in Krushinsky-Molodkina rats].
Krushinsky-Molodkina (KM) rats exhibit inherited susceptibility to audiogenic seizures and auditory stimuli induce generalized tonic-clonic seizures that resemble human epilepsy. The aim of this study was to compare the neurological manifestations of pentylenetetrazole (PTZ)-induced seizures in Wistar and KM rats to clarify the contribution of inherited susceptibility to audiogenic seizures, and to assess the anticonvulsant activity of NMDA receptor blockers memantine and IEM-1921 (1-phenylcyclohexylamine) in the PTZ-induced seizure model in KM rats. KM rats exhibited increased seizure severity relative to Wistar rats, and the death of KM rats was observed in 2.1 times more likely. Both NMDA receptor blockers showed anticonvulsant activity in the PTZ-induced seizure model, however IEM-1921 was more potent than memantine. IEM-1921 reduced the average intensity of the seizures by 2 points on a 5-point scale, and the total duration of generalized seizures was decreased by 41 times. IEM-1921 completely prevented the death of animals, while memantine only slightly decreased the mortality (68% in control conditions vs. 50% with administration of memantine). The results of the present study suggest that NMDA receptors are involved in the molecular mechanisms of seizures of different etiologies.


Myelodysplastic syndrome and associated coagulopathy: a case report and review.
Myelodysplastic syndrome (MDS) is a primary bone marrow disorder whose hallmark is the development of peripheral cytopenias and a predilection toward the development of acute myeloid leukemia (AML). Patients often have hypercellular bone marrows with dysplastic features that may involve multiple lineages. An increased awareness of MDS has led to the reporting of a number of associated autoimmune and paraneoplastic conditions in the medical literature. We present the case of an elderly man who was transferred to our institution with persistent, refractory bleeding several weeks after the resection of a sebaceous cyst. Despite reoperation, treatment with topical and intravenous hemostatic agents, and transfusion of blood products, the patient's bleeding persisted. A comprehensive evaluation for the cause of his coagulopathy was undertaken. Bone marrow evaluation was consistent with MDS. A paraneoplastic consumptive coagulopathy or fibrinolytic process in conjunction with MDS-related platelet dysfunction was felt to be the most likely etiology of the patient's bleeding.


Resident-intruder trait aggression is associated with differences in lysine vasopressin and serotonin receptor 1A (5-HT1A) mRNA expression in the brain of pre-pubertal female domestic pigs (Sus scrofa).
Aggressive behaviour exhibited by domestic pigs following encounters with unfamiliar individuals is a serious welfare and economical problem. Aggression resulting in skin lesions is similarly prevalent in prepubertal pigs of either sex. Little is known about the neural circuits and neuropeptides that control aggression in the pig. Because there is evidence for the involvement of the vasopressin and serotonergic systems in the regulation of aggressive behaviour in male mammals, we sought differences using quantitative in situ hybridisation of vasopressin and serotonin 1A receptor (5-HT1A) mRNA expression within specific brain regions of aggressive and nonaggressive prepubertal female pigs. The number of cells expressing vasopressin mRNA was significantly higher in aggressive pigs in the medial amygdala, lateral septum (LS) and showed a similar trend in the bed nucleus of the stria terminalis (BnST) but not the paraventricular nucleus (PVN) or supraoptic nucleus. The 5-HT1A receptor was widely expressed through the porcine brain and a significantly lower intensity (silver grain density) of 5-HT1A mRNA expression was observed in the BnST. In the medial amygdala and LS fewer cells expressed 5-HT1A mRNA in aggressive pigs but no differences were found in the PVN. In the absence of inbred strains or selection lines, these findings have shown that prior identification of phenotypic behavioural extremes in a population in advance of neural studies is a useful technique. Moreover, these findings support a central role for vasopressin and serotonin in the mediation of high trait aggression in prepubertal female pigs.


Exploring at the molecular level the effects of blood and blood-insulin cardioplegias used during open-heart surgeries on myocardial prevention.
The aim of this study was to measure the changes in the levels of soluble adhesion molecules involved in acute inflammation during ischemia-reperfusion in adults who underwent open-heart surgery using blood and blood-insulin cardioplegia and to examine the differences in tissue damage at the molecular level as a consequence of insulin's effect on myocardial energy metabolism. Non diabetic 36 patients were enrolled. Blood cardioplegia was used at all cases; insulin and glucose were added at the study group. Blood samples were taken from the coronary sinus and the radial artery before cross-clamp (T1), at 1st (T2) and 30th(T3) minutes after reperfusion. Soluble intercellular adhesion molecules-1 (sICAM-1), soluble vascular adhesion molecules-1 (sVCAM-1), soluble platelet/endothelial cells adhesion marker-1 (sPECAM-1) and serum lactate levels were measured in these samples. Cardiac enzymes (CK-MB, troponin, and myoglobin) were measured at postoperative 1th, 8th and 16th hours. The total duration of mechanical ventilatory support during postoperative period, and the number of days in the intensive care unit and hospital were recorded. No significant differences were observed in sVCAM-1 levels in blood taken from the radial artery at T1, T2 and T3 in either group. There were significant increases between T1 and T3 and between T2 and T3 in samples obtained form the coronary sinus (P=0.000 and P=0.003, respectively). Significant increases in sPECAM-1 in samples obtained from both sites between T2 and T3 in both groups (P=0.000) were observed. These differences were similar in both groups. Troponin levels at 8th and 16th hours in the blood-insulin cardioplegia group were higher than the blood cardioplegia group (P=0.003 and P=0.032, respectively). Supplementation of blood cardioplegia with insulin did not yield a significant improvement in adhesion molecules. Therefore, superiority of one cardioplegia over the other in delivering myocardial protection during open-heart surgery has not been shown.


Absolute noninvasive measurement of CO2 mole fraction emitted by E. coli and S. aureus using calibration-free 2f WMS applied to a 2004 nm VCSEL.
We report the first demonstration, to the best of our knowledge, of accurate real-time noninvasive measurement of the absolute cumulative mole fraction of metabolic carbon dioxide emitted by Escherichia coli and Staphylococcus aureus over a period of several hours of their life cycles using a recently developed calibration-free wavelength modulation spectroscopy technique. A 1 mW vertical-cavity surface-emitting laser is used to interrogate a single rotational vibrational absorption line of carbon dioxide at 2003.5 nm. The measurements are immune to laser intensity fluctuations and variable optical coupling that is inevitable in such free-space coupled experiments that run over 10-18 h. The cumulative carbon dioxide mole fraction follows the characteristic modified Gompertz model that is typical of bacterial growth in batch cultures. The characteristic growth parameters are extracted from this curve. The technique can be readily extended to study multiple volatile organic compounds that bacteria are known to emit.


Relevance of mutations in the TLR4 receptor in patients with gram-negative septic shock.
Septic shock remains a significant health concern worldwide, and despite progress in understanding the physiological and molecular basis of septic shock, the high mortality rate of patients with septic shock remains unchanged. We recently identified a common polymorphism in toll-like receptor 4 (TLR4) that is associated with hyporesponsiveness to inhaled endotoxin or lipopolysaccharide in humans. Since TLR4 is a major receptor for lipopolysaccharide in mammals and gram-negative bacteria are the prevalent pathogen associated with septic shock, we investigated whether these specific TLR4 alleles are associated with a predisposition to a more severe disease outcome for patients with septic shock. We genotyped 91 patients with septic shock as well as 73 healthy blood donor controls for the presence of the TLR4 Asp299Gly and TLR4 Thr399Ile mutations. We found the TLR4 Asp299Gly allele exclusively in patients with septic shock (P =.05). Furthermore, patients with septic shock with the TLR4 Asp299Gly/Thr399Ile alleles had a higher prevalence of gram-negative infections. Mutations in the TLR4 receptor may predispose people to develop septic shock with gram-negative microorganisms.


Application of EGFP-EGF fusions to explore mechanism of endocytosis of epidermal growth factor.
To develop a simple method for monitoring protein localization of epidermal growth factor (EGF) in living cells. Enhanced green fluorescent protein (EGFP) was used as an autofluorescent tag to label EGF ligands. SDS-PAGE and Western blot analysis were used to detect the expression of the EGFP-tagged EGF (EGFP-EGF) protein. The cell-binding and internalization activity of EGFP-EGF were analyzed by fluorescence-activated cell sorting (FACS) and confocal microscopy. EGFP-EGF protein was expressed in Escherichia coli and purified. A cell-binding assay demonstrated that the EGFP-EGF protein could bind efficiently to the cells expressing EGFR. The binding and internalization of EGFP-EGF can be visualized even at a very low concentration under confocal microscopy. The FACS-based assay for internalization activity indicated the accumulation of internalized EGFP-EGF over time. Furthermore, the results of the competition assay indicated its EGFR binding specificity. Using such a method, it does not need to label EGF with chemicals and avoid light in the experimental process. The fusion protein EGFP-EGF has several characters including high sensitivity, stability and convenience for manipulation, and is a powerful tool for the study of EGF endocytosis.


Predictors of one-year mortality after hospitalization for an exacerbation of COPD.
Hospitalization for a severe exacerbation of COPD (eCOPD) is an important event in the natural history of COPD. Identifying factors related to mortality 1 year after hospitalization could help determine interventions to reduce mortality. In a prospective, observational, multicentre study, we evaluated data from two cohorts: the Spanish audit of hospital COPD exacerbation care (our derivation sample) and the Spanish cohort of the European audit of COPD exacerbation care (our validation sample). The endpoint was all-cause mortality. Mortality was determined by local research managers of the participating hospitals and matched the official national index records in Spain. In the multivariate analysis, factors independently related to an increase in mortality were older age, cardio-cerebro-vascular and/or dementia comorbidities, PaCO2 > 55 mmHg measured at emergency department arrival, hospitalizations for COPD exacerbations in the previous year, and hospital characteristics. The area under the receiver-operating curve for this model was 0.75 in the derivation cohort and 0.76 in the validation cohort. One-year mortality following the index hospitalization for an exacerbation of COPD was related to clinical characteristics of the patient and of the index event, previous events of similar severity, and characteristics of the hospital where the patient was treated.


Electron microscope observations on compounds 48-80-induced degranulation in rat mast cells. Evidence for sequential exocytosis of storage granules.
In vitro degranulation of rat mast cells was studied at different intervals ranging from 10 to 60 sec after adding the histamine liberator, compound 48/80 (0.4 microg/ml, 17 degrees C). The ultrastructural changes were followed by electron microscopy, and parallel assays were made to determine the histamine released. In addition, the extracellular tracers lanthanum and hemoglobin (demonstrated by its peroxidative activity) were applied to mast cells to follow communication of the extracellular space with the cavities formed during degranulation. After a lag period of 10 sec, degranulation started in the most peripherally located granules. The perigranular membrane fused with the plasma membrane, resulting in a pore bridged by a thin diaphragm. This was followed by rupture of the diaphragm and extrusion of the granule matrix (exocytosis). The process advanced towards the cell interior by fusion and opening of the deeper situated granules to the formerly opened granule cavities. At the end of the process, the cell was filled by a system of complicated cavities containing a number of altered granules. Extracellular tracers have shown that these intracellular cavities were in unbroken communication with the extracellular space from the very beginning of their formation. Both lanthanum and hemoglobin were found to be adsorbed to the limiting membrane of the cavities and bound to altered mast cell granules. In contrast, no tracer substance was present in nondegranulating mast cells. Degranulation of mast cells by compound 48/80 is regarded as a sequential exocytosis, a process similar to that described for some exocrine gland cells. All the "intracellular" cavities, formed by degranulation, were shown to communicate with the extracellular space; consequently, granules lying in these cavities must be considered as biologically extracellular. The present findings support the view that histamine is released from the granule matrix by the extracellular ionic milieu.


Clinical relevance of inhaled corticosteroids and HPA axis suppression.
Although hypothalamic-pituitary-adrenal (HPA) axis suppression has traditionally been viewed as an adverse event after long-term administration of corticosteroids, this effect can also be used to compare the potency of different inhaled corticosteroids. However, various factors such as the dose, frequency of administration, treatment duration, study population (patients with asthma versus normal volunteers), and prior systemic steroid therapy influence adrenal suppression with inhaled corticosteroids. The different adrenal function tests available and the results produced with these tests also must be considered along with the clinical relevance of such results. Whereas low doses of inhaled corticosteroids are likely to cause minimal or no HPA axis suppression, long-term high-dose inhaled corticosteroid use may result in significant suppression by effectively replacing endogenous steroid production. The risk of acute adrenal insufficiency in patients taking low/medium-dose inhaled corticosteroids is minimal, but patients receiving long-term high-dose treatment may require supplementary systemic steroids during stress challenges, especially if they have previously received long-term systemic steroid treatment.