Features of the complex of food additive hesperidin to hemoglobin.
The purpose of the current work was to examine the complexation of a mammalian protein, hemoglobin (Hb) with a food additive hesperidin at physiological conditions. Molecular modeling, fluorescence, and circular dichroism (CD) methods were exploited to analyze the binding domain, affinity, and the effects of hesperidin conjugation on Hb spatial structure. From molecular modeling, central cavity of Hb was assigned to retain high-affinity for hesperidin, this corroborates the steady state fluorescence and hydrophobic ANS probe results. The association of hesperidin with Hb emerges fluorescence quenching via static type, this phenomenon display that the ground state complex formation with an affinity of 10(4)M(-1), and hypsochromic effect transpires. Additionally, the alterations of synchronous fluorescence, CD, and three-dimensional fluorescence suggest that the polypeptide chain of Hb partially folding after conjugation with hesperidin. The above data suggest that Hb plays a significant role in the plasma distribution and transportation of hesperidin and related dietary flavonoids.


Tricarboxylic acid cycle inhibition by Li+ in the human neuroblastoma SH-SY5Y cell line: a 13C NMR isotopomer analysis.
Li+ effects on glucose metabolism and on the competitive metabolism of glucose and lactate were investigated in the human neuroblastoma SH-SY5Y cell line using 13C NMR spectroscopy. The metabolic model proposed for glucose and lactate metabolism in these cells, based on tcaCALC best fitting solutions, for both control and Li+ conditions, was consistent with: (i) a single pyruvate pool; (ii) anaplerotic flux from endogenous unlabelled substrates; (iii) no cycling between pyruvate and oxaloacetate. Li+ was shown to induce a 38 and 53% decrease, for 1 and 15 mM Li+, respectively, in the rate of glucose conversion into pyruvate, when [U-13C]glucose was present, while no effects on lactate production were observed. Pyruvate oxidation by the tricarboxylic acid cycle and citrate synthase flux were shown to be significantly reduced by 64 and 84% in the presence of 1 and 15 mM Li+, respectively, suggesting a direct inhibitory effect of Li+ on tricarboxylic acid cycle flux. This work also showed that when both glucose and lactate are present as energetic substrates, SH-SY5Y cells preferentially consumed exogenous lactate over glucose, as 62% of the acetyl-CoA was derived from [3-13C]lactate while only 26% was derived from [U-13C]glucose. Li+ did not significantly affect the relative utilisation of these two substrates by the cells or the residual contribution of unlabelled endogenous sources for the acetyl-CoA pool.


Evaluation of sticky traps for adult Aedes mosquitoes in Malaysia: a potential monitoring and surveillance tool for the efficacy of control strategies.
The present study compared the performance of sticky traps in order to identify the most effective and practical trap for capturing Aedes aegypti and Aedes albopictus mosquitoes. Three phases were conducted in the study, with Phase 1 evaluating the five prototypes (Models A, B, C, D, and E) of sticky trap release-and-recapture using two groups of mosquito release numbers (five and 50) that were released in each replicate. Similarly, Phase 2 compared the performance between Model E and the classical ovitrap that had been modified (sticky ovitrap), using five and 50 mosquito release numbers. Further assessment of both traps was carried out in Phase 3, in which both traps were installed in nine sampling grids. Results from Phase 1 showed that Model E was the trap that recaptured higher numbers of mosquitoes when compared to Models A, B, C, and D. Further assessment between Model E and the modified sticky ovitrap (known as Model F) found that Model F outperformed Model E in both Phases 2 and 3. Thus, Model F was selected as the most effective and practical sticky trap, which could serve as an alternative tool for monitoring and controlling dengue vectors in Malaysia.


Improved specific detection of Vibrio cholerae in environmental water samples by culture on selective medium and colony hybridization assay with an oligonucleotide probe.
We developed a rapid and efficient method based on culture on selective medium and colony hybridization assay for the detection of Vibrio cholerae in estuarine water samples. A 22-oligonucleotide sequence of the 16S-23S rDNA intergenic spacer region was labeled with digoxigenin and evaluated for specificity and sensitivity by dot blot and colony hybridization with collection strains and environmental and clinical isolates. No isolates of species other than V. cholerae hybridized with the oligonucleotide probe. Colony hybridization was then performed with mixed microbial populations from brackish and sea water samples isolated, after an enrichment step, on selective culture media. Plating on alkaline nutrient agar without added NaCl (modified alkaline nutrient agar, mANA) resulted in higher V. cholerae colony counts than did plating on other frequently used selective media, and favored direct detection by colony hybridization. The combined use of mANA agar and an oligonucleotide probe resulted in the specific recovery of V. cholerae and could be used for confirmation of the most-probable-number procedure usually used to count this bacterium in environmental samples.


Upregulation of let-7f-2-3p by long noncoding RNA NEAT1 inhibits XPO1-mediated HAX-1 nuclear export in both in vitro and in vivo rodent models of doxorubicin-induced cardiotoxicity.
Clinical application of doxorubicin (Dox) is limited due to its undesirable side effects, especially cardiotoxicity. Several microRNAs (miRNAs) such as microRNA-140-5p and miR-23a aggravate Dox-induced cardiotoxicity. Here we demonstrate that upregulation of miRNA let-7f-2-3p by long noncoding RNA (lncRNA) NEAT1 inhibits exportin-1 (XPO1)-mediated nuclear export of hematopoietic-substrate-1 associated protein X-1 (HAX-1) in Dox-induced cardiotoxicity. Treatment of the H9c2 cells with the Dox (1 μM) for 6 h inhibited HAX-1 nuclear export and decreased XPO1 expression. Overexpression of XPO1 significantly attenuated the Dox-induced leakage of myocardial enzymes (creatine phosphokinase, creatine kinase-MB and lactate dehydrogenase) and cardiomyocyte apoptosis with the increased HAX-1 nuclear export. Differentially expressed miRNAs including let-7f-2-3p were selected from the Dox or vehicle-treated cardiomyocytes. TargetScan and luciferase assay showed that let-7f-2-3p targeted XPO1 3' UTR. Inhibition of let-7f-2-3p reduced Dox-induced cardiotoxicity and apoptosis by inhibiting XPO1-mediated HAX-1 nuclear export, whereas let-7f-2-3p overexpression aggravated these effects. In addition, lncRNA NEAT1 was identified as an endogenous sponge RNA to repress let-7f-2-3p expression. Overexpression of lncRNA NEAT1 abolished the increased let-7f-2-3p expression by Dox, and thereby attenuated cardiotoxicity. The loss function of let-7f-2-3p increased XPO1-mediated HAX-1 nuclear export and reduced myocardial injury in Dox (20 mg/kg)-treated rats. Importantly, let-7f-2-3p inhibition in mice alleviated Dox-induced cardiotoxicity and preserved the antitumor efficacy. Together, let-7f-2-3p regulated by lncRNA NEAT1 aggravates Dox-induced cardiotoxicity through inhibiting XPO1-mediated HAX-1 nuclear export, and may serve as a potential therapeutic target against Dox-induced cardiotoxicity.


Altered formation of topotecan-stabilized topoisomerase I-DNA adducts in human leukemia cells.
Topotecan (TPT) is a topoisomerase I (topo I) poison that has shown promising antineoplastic activity in solid tumors and acute leukemia. In the present study, a band depletion assay was used to evaluate the ability of TPT to stabilize topo I-DNA adducts in human leukemia cell lines and in clinical leukemia samples ex vivo. This assay showed that 50% of the cellular topo I in HL-60 human myelomonocytic leukemia cells became covalently bound to DNA at an extracellular TPT concentration of 4 micromol/L. In contrast, in 13 clinical specimens of human leukemia harvested before treatment of patients with TPT, the TPT concentration required to stabilize 50% of the cellular topo I in topo I-DNA complexes ranged from 3 to greater than 100 micromol/L (median, 30 micromol/ L). Flow microfluorimetry showed that cellular TPT accumulation varied over only a twofold range and failed to provide evidence for transport-mediated resistance in the clinical samples. These observations raise the possibility that formation of topo I-DNA adducts is diminished in many specimens of refractory/relapsed acute leukemia by a mechanism that might alter topo I sensitivity to TPT.


Neurocognitive assessment on a tablet device: Test-retest reliability and practice effects of ANAM Mobile.
New technology has allowed for the transition of computerized neurocognitive assessments to increasingly user-friendly mobile platforms. While this increased portability facilitates neurocognitive assessment in a wider variety of settings, this transition necessitates further examination of the psychometric properties of tests that have been previously validated on alternate platforms. The present study evaluated the test-retest reliability and practice effects for a new version of the Automated Neuropsychological Assessment Metrics (ANAM), ANAM Mobile, designed to be administered on a tablet computer. A total of 108 undergraduate students completed ANAM Mobile and returned after one week for repeated testing. Observed test-retest reliabilities were consistent with previously established estimates across similar time intervals and ranged from .55 (Simple Response Time) to .87 (Matching to Sample). Modest practice effects were observed. Base rates of reliable decline were low and suggested that declines on two or more tests are uncommon among healthy college students. The present study demonstrates that ANAM Mobile subtests have good-to-excellent reliability across a 7-day retest interval with minimal practice effects. Future research should explore within-subject reliability across repeated ANAM administrations on a tablet device and further examine retest reliabilities over varying time courses and in more diverse samples.


The importance of the C-terminal amide structure of rat pancreastatin to inhibit pancreatic exocrine secretion.
A C-terminal fragment of rat pancreatatin, a 26 residue peptide amide and a fragment without a C-terminal amide were synthesized by Fmoc-based solid phase methods and their biological activities were compared. The rat C-terminal fragment inhibited pancreatic exocrine secretions produced by the intravenous injection of 2-deoxy-D-glucose (a central vagal nerve stimulation), whereas the fragment without a C-terminal amide showed no effect on pancreas. These results indicate that the C-terminal amide of this peptide is necessary to reveal its biological activity.


Analysis of human CYP7A1 mRNA decay in HepG2 cells by reverse transcription-polymerase chain reaction.
The conversion of cholesterol to bile acids is the major pathway through which cholesterol is removed from the body. The initial and rate-limiting step in this catabolic pathway is catalyzed by the liver-specific enzyme cholesterol 7alpha-hydroxylase (CYP7A1). The HepG2 cell line has been used as a model to study human CYP7A1. The levels of CYP7A1 mRNA, however, are quite low in this cell line and require the use of poly(A)+ mRNA for detection using standard Northern analysis. As an alternative, we established a reverse transcription-polymerase chain reaction (RT-PCR) assay that can be used to study CYP7A1 mRNA in HepG2 cells. Using RT-PCR, we analyzed the influence of cell culture conditions on CYP7A1 mRNA levels. We observed an increase in CYP7A1 mRNA levels as the density of the cell culture increased. This rise in CYP7A1 was accompanied by a reciprocal drop in the levels of the proto-oncogene c-myc. Since c-myc expression is strongly associated with cell growth status, this inverse relationship suggests that conditions that favor reduced cell proliferation result in higher levels of CYP7A1 expression. We also established the validity of using RT-PCR for the measurement of mRNA decay rates using c-myc and glyceraldehyde-3-phosphate dehydrogenase mRNAs as a model: The same half-life value was obtained for the c-myc mRNA using either Northern analysis or RT-PCR. Using our RT-PCR method we determined that human CYP7A1 mRNA decays with a half-life of 4.6 +/- 0.9 h (n = 8) in HepG2 cells. We show that the protein synthesis inhibitor cycloheximide prolonged the CYP7A1 mRNA half-life, suggesting that translation is required for mRNA decay. Dexamethasone treatment, however, did not alter CYP7A1 mRNA decay rate but it increased CYP7A1 steady-state mRNA levels, suggesting that the effect of this glucocorticoid in HepG2 cells may be transcriptional.


Attachment security, personality, and adjustment of elementary school children.
Children's development is assumed to be closely related to their attachment security and their personality. The authors' aim was to examine the joint contribution of attachment security and personality traits to children's adjustment by examining diverse children's outcomes (emotional symptoms, social functioning, and behavioral problems) and using various perspectives (children, parents, and teachers). The sample comprised 247 8-12-year-old children from low socioeconomic status neighborhoods. Personality and attachment contribute to the different domains of adjustment. In cases of moderation, attachment security moderates the implications of personality traits on children's adjustment. The findings highlight the contribution of positive personality tendencies in playing down the difficulties of insecurely attached children.


Topiramate for Tourette's syndrome in children: a meta-analysis.
To assess the efficacy and safety of topiramate for children with Tourette syndrome. Randomized controlled trials evaluating topiramate for children with Tourette syndrome were identified from the Cochrane library, PubMed, Cochrane Central, Embase, CBM, CNKI, VIP, WANG FANG database, and relevant reference lists. Two reviewers independently selected trials, assessed trial quality, and extracted the data. Disagreement was resolved by discussion. Quality assessment referred to the Cochrane Handbook for Systematic Reviews of Interventions (version 5.0.1.). Fourteen trials involving 1003 patients were included, of which 720 cases were male (71.8%). Ages were 2 to 17 years old. The general quality of included randomized controlled trials was poor. All trials were positive drug-controlled (12 randomized controlled trials used haloperidol as control, 2 used tiapride). The follow-up period was from 20 days to 12 months. Meta-analysis of 3 trials (n = 207), in which tics symptoms control was assessed by Yale Global Tic Severity Scale, suggested that there was significant difference in the mean change of Yale Global Tic Severity Scale score during the treatment period (mean difference = -7.74, 95% CI [-10.49, -4.99], I(2) = 0) between topiramate and control groups. Meta-analysis of 9 trials (n = 668) evaluating tics symptoms control ≥ 50% suggested that there was no significant difference in reduction of tics between topiramate and control group during the treatment period (relative ratio = 1.36, 95% CI [0.90, 2.06], I(2) = 0). Adverse events were reported in 13 trials. Drowsiness (3.3-16%), loss of appetite (4-16.7%), cognitive dysfunction (7.89-12.5%), and weight loss (6-10.5%) were common adverse events. The current evidence is promising but not yet sufficient to support the routine use of topiramate for Tourette syndrome in children due to low quality of the study designs. It deserves to confirm in further high-quality, placebo-controlled trials.


Gaetbulimicrobium brevivitae gen. nov., sp. nov., a novel member of the family Flavobacteriaceae isolated from a tidal flat of the Yellow Sea in Korea.
A Gram-negative, non-spore-forming and rod-shaped gliding bacterium, designated strain SMK-19T, was isolated from a tidal flat sediment of the Yellow Sea, Korea, and its taxonomic position was investigated by using a polyphasic approach. Strain SMK-19T grew optimally at 37 degrees C, in the presence of 2-3 % (w/v) NaCl and at pH 7.0-8.0. It contained MK-6 as the predominant menaquinone, and iso-C(17 : 0) 3-OH and iso-C(15 : 0) as the major fatty acids. Major polar lipids were phosphatidylethanolamine, unidentified phospholipids and an amino-group-containing lipid that is ninhydrin-positive. The DNA G+C content was 36.0 mol%. Phylogenetic analyses based on 16S rRNA gene sequences demonstrated that strain SMK-19T formed a distinct evolutionary lineage within the family Flavobacteriaceae. The 16S rRNA gene sequence of strain SMK-19T exhibited similarity values of <94.4 % to those of other members of the family Flavobacteriaceae. Strain SMK-19T was distinguished from phylogenetically related genera by differences in several phenotypic properties. On the basis of phenotypic, phylogenetic and chemotaxonomic data, SMK-19T (= KCTC 12390T = DSM 17196T) was classified at the type strain of a novel genus and species, Gaetbulimicrobium brevivitae gen. nov., sp. nov.


Volar radioscapholunate arthrodesis for malunited distal radius fracture with unsalvageable wrist articular degeneration: case report.
Fractures of the distal radius occur commonly, and volar plating has emerged as a current, successful, and popular treatment for this injury. When this technology fails, salvage procedures must be selected that aim to maximize wrist motion and minimize pain. We present a case of volar radioscapholunate wrist arthrodesis in the setting of unfeasible intraoperative volar osteotomy to treat a malunited distal radius fracture.


Progressive liver injury in chronic hepatitis C infection correlates with increased intrahepatic expression of Th1-associated cytokines.
An imbalance between T helper cell (Th)1 and Th2-like cytokines has been described in several chronic infectious diseases. We therefore analyzed the intrahepatic messenger RNA (mRNA) expression of Th1-like (interleukin [IL]-2, interferon [IFN]-gamma) and Th2-like (IL-4, IL-10) cytokines in chronic hepatitis C patients (n = 17) and controls (n = 6) and correlated the results with liver histology and intrahepatic viral load. Intrahepatic cytokine mRNA and hepatitis C virus (HCV) RNA were quantitatively assessed by polymerase chain reaction (PCR) using a dot-blot hybridization technique. Liver biopsy specimens were histologically graded using the Scheuer Score. IFN-gamma and IL-2 mRNA expression were significantly upregulated in chronic HCV vs. controls (P < .002, P < .04, respectively). Both correlated significantly with histological fibrosis and portal tract inflammation. In contrast, the expression of IL-10 mRNA was decreased in cirrhosis and chronic HCV compared with controls (P < .02, P < .0001, respectively). IL-4 mRNA was detected inconsistently at low levels in all groups. Intrahepatic viral load did not correlate with either cytokine expression or tissue injury. In conclusion, the progressive liver injury seen in chronic HCV is associated with the upregulation of intrahepatic Th1-like cytokines and the downregulation of IL-10, a Th2-like cytokine. These results suggest a role for delayed-type hypersensitivity immune reactions in HCV related liver injury.


Facile fabrication of branched gold nanoparticles by reductive hydroxyphenol derivatives.
In nature, polyphenol is one of the most important chemicals in many reductive biological reactions widely found in plants and animals. In this study, we demonstrated that hydroxyphenol compounds and their derivatives could be used as versatile reducing agents for facile one-pot synthesis of gold nanoparticles with diverse morphological characters by reducing precursor Au(III) ions into a gold crystal structure via a biphasic kinetically controlled reduction process. We found that the biphasic reduction of hydroxyphenols generated single-crystalline branched gold nanoparticles having high-index facets on their surface. The kinetically controlled self-conversion of hydroxyphenols to quinones was mainly responsible for the generation of morphologically different branches on the gold nanoparticles. Different hydroxyphenol derivatives with additional functional groups on the aromatic ring could produce totally different nanostructures such as nanoprisms, polygonal nanoparticles, and nanofractals possibly by inhibiting the self-conversion or by inducing self-polymerization. In addition, polymeric hydroxyphenol derivatives generated stably polymer-coated spherical gold nanoparticles with controlled size, usefully applicable for biomedical applications.


Academic Performance-Based Compensation Models.
Academic radiologists spend considerable amounts of time and effort providing nonclinical value-added services in the realms of teaching, research, and administration that are not reimbursable through traditional relative value units (RVUs) under the resource-based relative value scale. Numerous systems of academic RVUs have been proposed by medicine, surgery, and radiology programs to measure and reward these nonclinical contributions. In this article the authors (1) describe the traditional clinical RVU model of reimbursement; (2) review attempts to develop academic compensation models targeted toward research, teaching, and administration; and (3) describe possible models for academic productivity compensation.


Transition to the new role of caregiving for families of patients with breast cancer: a qualitative descriptive exploratory study.
Families, especially in Eastern and Muslim countries, routinely accept the responsibility of caring for cancer patients. This study describes the transition to the new role of caregiving from the perspective of family caregivers in Iran as part of the current trend of recognizing the experiences of family members of breast cancer patients from different cultural perspectives. A descriptive exploratory qualitative research approach was used to investigate the experiences of family caregivers of patients with breast cancer in the transition to caregiving. The subjects were 23 family caregivers of breast cancer patients referred to cancer centers at Isfahan University hospitals who were selected by purposive sampling. Data was gathered through in-depth interviews. Interview transcripts were analyzed using conventional content analysis with an inductive approach. Data analysis identified the following categories: grasping a new situation without preparation, perceived inefficiency, infinite absence, and abandoned in the role. Caregivers believed that they were not prepared for their new circumstances and did not have the necessary competence and capabilities to meet the challenges of caregiving. They experienced negative consequences resulting from the difficult responsibility of caregiving. Moreover, they believed that they received limited support from relatives, health-care providers, and the community. The transition to the new role of caregiving is affected by experiences specific to the conditions of the caretakers. When these conditions can be understood and identified, it is possible to provide detailed information for policymaking and planning for family-centered care.


[In vitro interaction between persisting oocysts of Cryptosporidium parvum and murine resident peritoneal macrophages. I. Effect of parasite on macrophage capability for oxidative burst].
Cryptosporidiosis in an opportunistic infection which poses a significant threat to the immunodeficient patients (including people with AIDS). The aim of the present work was to study whether oxidative burst, known as a nonspecific immune response of macrophages, may be modulated in vitro by persisting oocysts of a coccidian pathogen Cryptosporidium parvum. Live oocysts of C. parvum engulfed by murine perithoneal macrophages may persist within the phagosomes and retain their initial morphology for about 7 days following oocyst injection into macrophage monolayer. A short-term interaction of adherent macrophages with C. parvum oocyst suspension for 5-15 min caused oxidative burst in these macrophages. After a while, the intensity of this oxidative burst smoothly decreased to vanish within the following 2-6 h oocyst-macrophage cultivation. Dead oocysts caused no oxidative burst in macrophages. Co-cultivation of macrophages with oocysts for 1.0-1.5 days led to the appearance of macrophages, which had oocysts both contacting the cell surface and existing inside the phagosomes. In these macrophages the oxidative burst in response to the addition of a chemotactic peptide (fMLP) was considerably higher than in uninfected control cells. During a 1-4 day co-cultivation, the degree of oxidative burst caused by fMLP in macrophages containing only phagocytosed oocysts did not differ from that in the non-infected (oocyst-free) control. The data obtained enable us to propose that the products of oxidative burst in macrophages, formed in response to the interaction with C. parvum oocysts, do not kill the oocysts. These can survive for a long time in the phagosomes of macrophages. Such a long persistence of oocysts in phagosomes does not affect the capability of macrophages for oxidative burst in response to the action of fMLP.


A strategy for antitumor vascular therapy by targeting the vascular endothelial growth factor: receptor complex.
Vascular endothelial growth factor (VEGF) is produced by cancer cells in response to hypoxia and is the primary stimulant of vascularization in solid tumors. Endothelial cells lining the blood vessels of these tumors have a high concentration of receptor-bound VEGF on their surface, providing a target for antibody- directed cancer therapy. To obtain a cloned antibody to this target when bound to its receptor on tumor endothelium, we used phage display technology to create a single-chain Fv (sFv) antibody library from mice immunized with the 165-amino acid isoform of human VEGF-A. We selected, purified, and characterized LL4, an anti-VEGF sFv that was shown to react with receptor-bound VEGF. LL4 bound selectively to blood vessel endothelium, as shown by immunohistochemistry on tissue sections of human tumors. Furthermore, using autoradiography and grain counting of histological sections, systemically administered LL4 was shown to localize selectively to the endothelial lining of tumor blood vessels in human colorectal carcinoma xenografts in vivo. This study demonstrates the feasibility of targeting tumor vasculature using recombinant antibodies to the VEGF:receptor complex.


Poisson ratio and excess low-frequency vibrational states in glasses.
In glass, starting from a dependence of the Angell's fragility on the Poisson ratio [V. N. Novikov and A. P. Sokolov, Nature 431, 961 (2004)], and a dependence of the Poisson ratio on the atomic packing density [G. N. Greaves, A. L. Greer, R. S. Lakes, and T. Rouxel, Nature Mater. 10, 823 (2011)], we propose that the heterogeneities are predominantly density fluctuations in strong glasses (lower Poisson ratio) and shear elasticity fluctuations in fragile glasses (higher Poisson ratio). Because the excess of low-frequency vibration modes in comparison with the Debye regime (boson peak) is strongly connected to these fluctuations, we propose that they are breathing-like (with change of volume) in strong glasses and shear-like (without change of volume) in fragile glasses. As a verification, it is confirmed that the excess modes in the strong silica glass are predominantly breathing-like. Moreover, it is shown that the excess breathing-like modes in a strong polymeric glass are replaced by shear-like modes under hydrostatic pressure as the glass becomes more compact.


[Dilatation tracheotomy after Ciglia--its use in an internal-medicine intensive care unit].
Since the first description of percutaneous dilatation tracheostomy (DTT), it has become an alternative method of equal value to surgical tracheostomy. This study collected the experience with DTT in a medical intensive care unit (ICU), with special reference to early and late complications and their management, outcome, and changes in ventilation parameters and blood gases. Between March 1994 and April 1998, 74 DTTs were performed on 71 patients (52 men, 19 women; mean age 61.8 [30-80]) years. The admission or main diagnoses were cardiovascular disease in 34 patients, pulmonary disease in 21, the remainder having had a variety of conditions. The procedure caused complications in 21 procedures (28%): 10 cases of stomal bleeding (13.5% of total number of procedures), 2 of intratracheal bleeding (2.7%), 2 of severe tracheal injury (2.7%) and mediastinal emphysema in 1 (1.3%). None required intervention because of these complications. 38 patients were discharged from hospital. Cause of death in the other 33 was unrelated to the DTT. One patient developed tracheomalacia as a late complication. Ventilatory parameters and blood gases 12 hours post-DTT were the same as before the procedure. Ciaglia's method of dilatation tracheostomy is a safe procedure also in the context of a medical ICU, if the indications are correct and the procedure performed by experienced personnel. Compared with surgical tracheostomy it significantly reduces the burden on the patient as well as requiring fewer personnel and less equipment.


[HPV and cancer].
Human papillomavirus (HPV) has been largely demonstrated involved in the pathogenesis of several intraepithelial lesions and cancers. The role of HPV in the carcinogenesis of intraepithelial and invasive anogenital lesions is currently well established, characterized by integrated DNA HPV inside the lesions. HPV genotypes are classified according to their risk of oncogenesis and HPV16 remains the most common and higher oncogenic types. HIV-infected patients have a higher rate of HPV infection with a higher persistence and higher viral loads than general population, which can explain the increasing risk of cancers in such patients. However, independently of HIV infection, HPV infections seems to be strongly associated with several neoplasms, including head and neck, oral, cervical, anal, vulvar, vaginal cancers and probably some lung cancers. Paradoxically, little information about the immunity role and virological factors involved in the occurrence and outcome of HPV epithelial lesions are currently available, leading to more effective and biological approaches, in this HPV infection setting.


Label-free DNAsensor with PCR-like sensitivity based on background reduction and target-triggered polymerization amplification.
In this work, we have developed a highly sensitive and label-free DNAsensor for nucleic acid detection based on background noise reduction by exonuclease I (Exo I) and target-triggered cycled polymerization amplification. This DNAsensor consists of a long-tail probe, a short primer and polymerase. In the absence of the target, the long-tail probe and short primer are digested by Exo I, which minimizes the intercalation of fluorescence dye and reduces the background noise. In the presence of the target, the specific binding between the long-tail probe and the target triggers cycled polymerization reactions to form long dsDNA products. These long dsDNA products prevent effectively them from degrading by Exo I and amplify the fluorescence signals. In our sensing approach, the combination of the ExoI-assisted background reduction with the cycled polymerization amplification allows us to achieve a PCR-like sensitivity without labeling, washing separation and temperature cycles in a homogenous solution. Using total RNA samples extracted from hepatitis C virus (HCV) as targets, we further demonstrate the detection capability of the DNAsensor for complex nucleic acid samples, indicating its potential applicability for clinic molecular diagnostic assays.


Approach to salvage antiretroviral therapy in heavily antiretroviral-experienced HIV-positive adults.
Despite dramatic declines in HIV-associated morbidity and mortality as a result of highly active antiretroviral therapy, management of heavily treatment-experienced patients remains complex and challenging. Treatment response rates with subsequent antiretroviral regimens are lower than with initial antiretroviral therapy. Additionally, increased mortality has been associated with multidrug-resistant HIV. We review data relevant to management of such patients and offer a systematic approach to constructing a salvage antiretroviral regimen.


BioEnterics Intragastric Balloon (BIB) versus Spatz Adjustable Balloon System (ABS): Our experience in the elderly.
The BioEnterics Intragastric Balloon (BIB) and the Spatz Adjustable Balloon System (ABS) are in fact recommended for weight reduction as a bridge to bariatric surgery. We retrospected studied patients with body mass index (BMI) and age ranges of 37-46 and 70-80 years, respectively, who had undergone BIB from January 2010 to July 2012 and prospected studied patients who had undergone Spatz balloon from July 2012 to August 2014. The aim of this study is to compare BIB and Spatz in terms of weight loss, complications, and maintenance of weight after removal. For both procedures, the median weight loss was 20 ± 3 kg, median BMI at the end of the therapy was 32 ± 2, and no severe complication occurred.


Fetus in fetu.
A 2-month-old boy was found to have an abdominal mass in the left upper quadrant. Surgical removal revealed the mass to be a fetus in fetu. Dissection and roentgenologic examination unequivocally demonstrated the presence of vertebral column and organs arranged appropriately to the vertebral axis.


Assessing modified risk tobacco and nicotine products: Description of the scientific framework and assessment of a closed modular electronic cigarette.
Cigarette smoking causes many human diseases including cardiovascular disease, lung disease and cancer. Novel tobacco products with reduced yields of toxicants compared to cigarettes, such as tobacco-heating products, snus and electronic cigarettes, hold great potential for reducing the harms associated with tobacco use. In the UK several public health agencies have advocated a potential role for novel products in tobacco harm reduction. Public Health England has stated that "The current best estimate is that e-cigarettes are around 95% less harmful than smoking" and the Royal College of Physicians has urged public health to "Promote e-cigarettes widely as substitute for smoking". Health related claims on novel products such as 'reduced exposure' and 'reduced risk' should be substantiated using a weight of evidence approach based on a comprehensive scientific assessment. The US FDA, has provided draft guidance outlining a framework to assess novel products as Modified Risk Tobacco Products (MRTP). Based on this, we now propose a framework comprising pre-clinical, clinical, and population studies to assess the risk profile of novel tobacco products. Additionally, the utility of this framework is assessed through the pre-clinical and part of the clinical comparison of a commercial e-cigarette (Vype ePen) with a scientific reference cigarette (3R4F) and the results of these studies suggest that ePen has the potential to be a reduced risk product.


Role of food-derived antioxidants against cisplatin induced-nephrotoxicity.
Cancer is a relevant public health problem that represents the second leading cause of global death. In this regard, cisplatin is a highly effective antineoplastic drug used in treatment of several types of cancer, such as head and neck, testicular, ovarian, gastric, lung and breast cancer. Nevertheless, treatment with this compound leads to nephrotoxicity, which limits its use. Oxidative stress plays a pivotal role in cisplatin-induced renal damage and several dietary antioxidants have been reported to ameliorate this secondary effect. Relevant findings on the protective effects of these antioxidant agents in cisplatin-induced nephrotoxicity are summarized in this paper. Further, limitations of animal models used in these studies are discussed. Additionally, clinical studies on the protective effect of these antioxidants, as well as future directions for these kind of trials are also considered.


Malformations of neocortical development: magnetic resonance imaging correlates.
Malformations of cortical development are a significant cause of epilepsy in adults and of developmental delay and epilepsy in children. Magnetic resonance imaging allows many of these malformations to be detected noninvasively. In the past year, the major work in this area has been aimed at improved detection of small areas of dysplasia, further identification of clinicomorphological syndromes associated with these disorders, and early attempts to classify these malformations based upon clinical and magnetic resonance criteria.


The dimerization of folded monomers of ribulose 1,5-bisphosphate carboxylase/oxygenase.
Spontaneous refolding and reconstitution processes of dimeric ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) from Rhodospirillum rubrum have been investigated using size-exclusion high performance liquid chromatography (HPLC), spectroscopic, and activity measurements. When the unfolded Rubisco in guanidine hydrochloride is diluted at 4 degrees C, a folding intermediate (Rubisco-I) is rapidly formed, which remains in an unstable monomeric state and gradually develops into folded monomer (Rubisco-M) at 4 degrees C but undergoes irreversible aggregation at 25 degrees C. Refolding of Rubisco-I to Rubisco-M is a very slow process, taking about 20 h for 70% conversion at 4 degrees C. Rubisco-M is stable at 4 degrees C and is capable of forming an active dimer spontaneously when incubated at a temperature higher than 10 degrees C. The dynamic dimerization process has been measured in a temperature range of 4-35 degrees C by HPLC, and the results demonstrate that the dimerization is strongly facilitated by the temperature. It is found that dithiothreitol is essential for the spontaneous reconstitution of Rubisco.


Assessment of renal function in renal transplant patients using cystatin C. A comparison to other renal function markers and estimates.
To date, little evidence is available to define the role of cystatin C in patients with renal transplants. Thus, to assess, whether cystatin C (CysC) provides better information on renal function than other markers, CysC, creatinine clearance (CrCl), serum creatinine (SCr), beta2-microglobulin (beta2-M), and 125I-Iothalamate clearance were determined in 30 patients. Correlation and ROC curves were obtained and characteristics like sensitivity and specificity were calculated. Further, to evaluate the usefulness of these markers for monitoring, intraindividual coefficients of variation for CysC and SCr measurements were compared in 85 renal transplant patients. CysC correlated best with GFR, whereas SCr, CrCl and beta2-M all had lower correlation coefficients. CysC was superior to SCr, even when renal function equations of were used. The diagnostic accuracy of CysC was significantly better than SCr. but did not differ significantly from CrCl and beta2-M. Together, our data show that in patients with renal transplants, CysC has a similar diagnostic value as CrCl. However, it is superior to determinations of SCr. The intraindividual variation of CysC is significantly greater than that of SCr. This might be due to better ability of CysC to reflect temporary changes especially in mildly impaired GFR, most critical for early detection of rejection and other function impairment. In conclusion, CysC allows for easy and accurate assessment of renal function (GFR) in steady state renal transplant patients and is clearly superior to the commonly used serum creatinine.


Influence of hypoxia and acidity on thermal radiosensitization and direct heat-induced death of BP-8 sarcoma cells.
The response to heat of BP-8 murine sarcoma cells was evaluated with the 125I-iodo-deoxyuridine prelabeling technique. Euoxic and hypoxic BP-8 cells were heated in vitro at pH 7.4 vs. 6.5 at temperatures ranging from 37 degrees C to 44 degrees C. The results indicated that acute hypoxia had no effect on either heat potentiation of radiation damage or direct heat-induced death. However, lowering of media pH increased direct thermal cell death and, to a lesser extent, heat potentiation of radiation lethality. These findings suggest that the enhanced radiosensitization and heat-induced death observed in chronically hypoxic tumor populations may, at least in part, be caused by hypoxia-induced tumor acidification.


Mechanism of NaCl secretion in the rectal gland of spiny dogfish (Squalus acanthias). I. Experiments in isolated in vitro perfused rectal gland tubules.
Rectal gland tubules (RGT) of spiny dogfish were dissected and perfused in vitro. Transepithelial PD (PDte), resistance (Rte), the PD across the basolateral membrane (PDbl) and intracellular chloride and potassium activities (a cell Cl-, a cell K+) were measured. In a first series, 67 RGT segments were perfused with symmetric shark "Ringers" solution. The bath perfusate contained in addition db-cAMP 10(-4), forskolin 10(-6), and adenosine 10(-4) mol X 1(-1). PDte was -11 +/- 1 (n = 67) mV lumen negative, Rte 27 +/- 2 (n = 47) omega cm2, PDbl -75 +/- 0.4 (n = 260) mV. a cell K+ and a cell Cl- were 109 +/- 22 (n = 4) and 38 +/- 4 (n = 36) mmol X 1(-1) respectively. These data indicate that Cl-secretion across the RGT must be an uphill transport process, whereas secretion of Na+ could be driven by the lumen negative PDte. Intracellular K+ is 14 mV above equilibrium with respect to the basolateral membrane PD and Cl- is 23 mV above equilibrium across the apical membrane. In series 2, the conductivity properties of the apical and basolateral membrane as well as that of the paracellular pathway were examined in concentration step experiments. Decrease of the basolateral K+ concentration led to a rapid hyperpolarization of PDbl with a mean slope of 19 mV per decade of K+ concentration change. Addition of 0.5 mmol X 1(-1) Ba2+ to the bath solution lead to a marked depolarization and abolished the response to K+ concentration steps. In the lumen a Cl- concentration downward step led to a depolarization of the lumen membrane; resulting in a mean slope of 18 mV per decade of Cl- concentration change. When dilution potentials were generated across the epithelium, the polarity indicated that the paracellular pathway is cation selective. In series 3 the equivalent short circuit current (Isc = PDte/Rte) was determined as a function of symmetrical changes in Na+ concentration, with Cl- held at 276 mmol X 1(-1), and as a function of symmetrical changes in Cl- concentration, with Na+ held at 278 mmol X 1(-1). Isc was a saturable function of Na+ concentration (Hill coefficient 0.9 +/- 0.1, K1/2 4.4 mmol X 1(-1), n = 7) and also a saturable function of Cl- concentration (Hill coefficient 2.0 +/- 0.1, K1/2 75 mmol X 1(-1), n = 11).(ABSTRACT TRUNCATED AT 400 WORDS)


Quantitative candidate gene association studies of metabolic traits in Han Chinese type 2 diabetes patients.
Recent genome-wide association studies have identified many loci associated with type 2 diabetes mellitus (T2DM), hyperuricemia, and obesity in various ethnic populations. However, quantitative traits have been less well investigated in Han Chinese T2DM populations. We investigated the association between candidate gene single nucleotide polymorphisms (SNPs) and metabolic syndrome-related quantitative traits in Han Chinese T2DM subjects. Unrelated Han Chinese T2DM patients (1975) were recruited. Eighty-six SNPs were genotyped and tested for association with quantitative traits including lipid profiles, blood pressure, body mass index (BMI), serum uric acid (SUA), glycated hemoglobin (HbA1c), plasma glucose [fasting plasma glucose (FPG)], plasma glucose 120 min post-OGTT (P2PG; OGTT = oral glucose tolerance test), and insulin resistance-related traits. We found that CAMTA1, ABI2, VHL, KAT2B, PKHD1, ESR1, TOX, SLC30A8, SFI1, and MYH9 polymorphisms were associated with HbA1c, FPG, and/or P2PG; GCK, HHEX, TCF7L2, KCNQ1, and TBX5 polymorphisms were associated with insulin resistance-related traits; ABCG2, SLC2A9, and PKHD1 polymorphisms were associated with SUA; CAMTA1, VHL, KAT2B, PON1, NUB1, SLITRK5, SMAD3, FTO, FANCA, and PCSK2 polymorphisms were associated with blood lipid traits; CAMTA1, SPAG16, TOX, KCNQ1, ACACB, and MYH9 polymorphisms were associated with blood pressure; and UBE2E3, SPAG16, SLC2A9, CDKAL1, CDKN2A/B, TCF7L2, SMAD3, and PNPLA3 polymorphisms were associated with BMI (all P values <0.05). Some of the candidate genes were associated with metabolic and anthropometric traits in T2DM in Han Chinese. Although none of these associations reached genome-wide significance (P < 5 x 10(-8)), genes and loci identified in this study are worthy of further replication and investigation.


Compensatory stepping: the biomechanics of a preferred response among older adults.
The purpose of this study was to evaluate age-related differences in the mechanics of the compensatory stepping response to balance threats. A moving platform was used to disturb the balance of 16 younger (21 to 35 years) and 19 older (68 to 88 years) adults. Backward platform translations consisted of 15-cm displacements with peak accelerations ranging from 9.4 to 15.2 m/s2. Older adults were more likely to use a step to recover balance and stepped at lower perturbation magnitudes than younger adults. Group differences were not found in time to step initiation or segmental momentum. The lack of group differences in momentum revealed that lower perturbation accelerations created an equivalent or greater magnitude of body motion in older adults compared to higher accelerations experienced by younger adults. Older adults also showed a reduced ability to attenuate the input acceleration and experienced significantly greater linear acceleration of the head.


Ion exchange column capacities. Predicting retention behavior of open tubular columns coated with the same phase.
We discuss the reported capacities of available packed ion exchange columns and the different methods used for their measurement. We outline basic considerations related to both packed and open tubular columns based on ion exchange latex particles. There is a large body of information covering the retention behavior of packed ion exchange columns based on ion exchange latex particles. We propose a parameter γiex, which is the ion exchange capacity of a column (packed or open tubular) per unit liquid volume present in the column (including accessible volume within pores) and show that the retention factor for any given ion is directly related to γiex. On this basis, if based on the same type of latex, the behavior of one type of column can be reasonably predicted from the known behavior of the other, even when the absolute capacities differ by more than 5 orders of magnitude.


Dr. Williams, a video and the day my world changed.
The messages of a Harvard professor's talk underline how much we need the Workforce Race Equality Standard.


[STANDARD TRANSCUTANEOUS AND ULTRA-MINI TRANSCUTANEOUS NEPHROLITHOTRIPSY IN TREATMENT OF NEPHROLITHIASIS].
Comparative analysis of two variants of transcutaneous nephrolithotripsy (TCNLT) in 45 patients, suffering nephrolithiasis, was performed. In 17 patients (the first group) the ultra-mini (UM) TCNLT, using tubus 11Сh, was done, and in 28 patients (the second group) – TCNLT, using a standard tubus 24Сh. The operation duration in the first group have had constituted (86.2 ± 16.3) min at average, and in the second group – (51 ± 13.6) min. The method of UМ TCNLT is a secure, miniinvasive, owing low rate of morbidity, comparing with a standard procedure, but with equal efficacy, concerning the «stone free» status (accordingly, 95.3 and 96.5%) in patients when calculi’s diameter up to 2 sm. Тubus 11Ch guarantees lesser risk of hemorrhagic complications occurrence, permits to conduct UM TCNLT without nephrostomic draining of the renal calyx and pelvis system more confidently.


Partogram action line study: a randomised trial.
To assess the effect of three different partograms on caesarean section and maternal satisfaction. Prospective randomised clinical trial. Regional teaching hospital in North West of England. Nine hundred and twenty-eight primigravid women with uncomplicated pregnancies who presented in spontaneous labour at term. The women were randomised to have their progress of labour recorded on a partogram with an action line 2, 3 or 4 hours to the right of the alert line. If the progress reached the action line, a diagnosis of prolonged labour was made. Prolonged labour was managed according to the standard ward protocol. Primary: Caesarean section rate and maternal satisfaction; secondary: need for augmentation, duration of labour, analgesia, cord blood gas analysis, postpartum haemorrhage, number of vaginal examinations, Apgar score and admission to special care baby unit. Caesarean section rate was lowest when labour was managed using a partogram with a 4-hour action line. The difference between the 3- and 4-hour partograms was statistically significant (OR 1 8, 95% CI 1.1-3.2), but the difference between 2 and 4 hours was not (OR 1.4, 95% CI 0.8-2.4). The women in the 2-hour arm were more satisfied with their labour when compared to the women in the 3-hour (P < 00001) and 4-hour (P <00001) arm. Our data suggest that women prefer active management of labour. It is possible that partograms which favour earlier intervention are associated with higher caesarean section rate. As the evidence on which to base the choice of partograms remains inconclusive further research is required.


Immunocytochemical detection of bcl-2 and p53 proteins in B-chronic lymphocytic leukemia patients.
B-cell chronic lymphocytic leukemia (B-CLL) is a disease with variable course and prognosis. It may be important to predict the possible risk of disease progression in individual patients. We have investigated by immunocytochemistry the bcl-2 and p53 protein expression in 53 B-CLL patients at the time of initial diagnosis. All B-CLL cases were bcl-2 protein positive. The relatively high frequency of p53 protein immunoreactivity was observed (17 of 53 cases; 32%). The percentage of bcl-2 and p53 protein positive cells remarkably varied in individual patients. The heterogeneity in the percentage of bcl-2 as well as p53 positive cells showed to be important in the analysis of mutual relation of these proteins. Noteworthy results were obtained when the group of p53 positive B-CLL patients was analyzed according to the percentage of p53 positive cells (less than 20% and more than 20%, respectively). An inverse relationship between a higher accumulation of p53 and repressed bcl-2 expression and vice versa was observed. The male patients (female patients were not assessed because of the limited number of p53 positive cases) with less than 20% p53 immunoreactive cells revealed a high percentage of bcl-2 protein (p=0.0008). The higher incidence (over 20%) p53 positive cells correlated with lowered percentage of bcl-2 positive cells (p=0.0368). When the patients were subdivided according to p53 positivity and negativity, the majority of p53 positive cases were males (82%), with significantly higher WBC count (p=0.0362). No significant effect of higher or lower WBC counts on bcl-2 and p53 expression was observed. However, the expression of bcl-2 protein was significantly higher in female patients under 50 years (p=0.0012). Regarding the patients of age <or=50 and >50, a significant difference in WBC count was shown in males (p=0.0590). The peripheral blood lymphocytes isolated from healthy subjects used as controls, exhibited undetectable, to low proportion of bcl-2 and p53 positive cells. Comparing the percentage of bcl-2 as well as p53 positive cells in controls and those of B-CLL patients, the significant difference for both proteins was observed (p=0.0009 and p=0.0001, respectively). The results of this study indicate that the overexpression of p53 protein may contribute to the downregulation of bcl-2 in a subgroup of our B-CLL patients. Considering the small numbers of tested p53 positive cases, it would be necessary to confirm our findings in a larger cohort of patients with longer follow up. Thus it would be possible to confirm our expectation of a possible value of the simultaneous aberrant expression of bcl-2 and p53 as useful predictors of future aggressive behavior of B-CLL.


Massive lower gastrointestinal bleeding from Meckel's diverticulum with heterotopic pancreas: case report and a brief review of the literature.
Heterotopic pancreas is defined as pancreatic tissue found out of the pancreas proper with no vascular or anatomical connection. It is a rare clinical entity and can be found at any portion of the alimentary system. We describe a case of Meckel's diverticulum with heterotopic pancreas who presented massive lower gastrointestinal bleeding. Lower gastrointestinal bleeding due to Meckel's diverticulum with heterotopic pancreas is extremely difficult to make a definitive diagnosis preoperatively especially when it onsets rapidly.


Fabrication of metallic nanowires and nanoribbons using laser interference lithography and shadow lithography.
Ordered and free-standing metallic nanowires were fabricated by e-beam deposition on patterned polymer templates made by interference lithography. The dimensions of the nanowires can be controlled through adjustment of deposition conditions and polymer templates. Grain size, polarized optical transmission and electrical resistivity were measured with ordered and free-standing nanowires.


Infected cephalohematomas and underlying osteomyelitis: a case-based review.
Cephalohematomas are relatively common sub-periosteal collections of blood that tend to resolve spontaneously without treatment. Rarely, they become infected and can be associated with underlying osteomyelitis, meningitis, or sepsis. Common pathogens include Escherichia coli and Staphylococcus species. This report describes the first case of a neonate developing an infected right parietal cephalohematoma and underlying osteomyelitis caused by Morganella morganii, which was cultured in blood and cephalohematoma aspirate. This infant male, whose risk factors included vacuum extraction during delivery and suspected post-natal pneumonia, responded well to a 6-week course of intravenous meropenem with complete resolution of both lesions. When an infected cephalohematoma is suspected, aspiration of hematoma fluid should be performed for both diagnostic and therapeutic purposes. Infectious symptoms should warrant prompt investigation and treatment, which may include drainage, debridement, and antibiotics. This report demonstrates that the combination of an infected cephalohematoma and underlying osteomyelitis might not be as uncommon as previously believed.


Trait-agreeableness influences individual reactions to a physician's affiliative behavior in a simulated bad news delivery.
We tested whether the personality trait of agreeableness predicts different individual reactions to the level of nonverbal affiliativeness shown by a physician, in the context of a simulated bad news delivery. We predicted that individuals with high levels of agreeableness would react better to a physician adopting a highly affiliative communication style compared to individuals with low levels of agreeableness. We used an experimental design with analogue patients. Eighty participants (40 men/40 women) were randomly assigned to watch a video of a physician who communicated a bad diagnosis either in a highly affiliative or in a less affiliative way. Participants reported their reactions of anger and trust in the physician, and completed the agreeableness scale of the NEO Five-Factor Inventory (NEO-FFI). In accordance with our predictions, the higher the agreeableness score of the participants, the less anger and the more trust they reported after viewing the high as compared to the low affiliative physician. These results suggest that people with high levels of agreeableness may be especially sensitive to highly affiliative physician nonverbal behavior when receiving bad news.


Chronic hypokalemia due to gastric exclusion after bariatric surgery.
Hypokalemia is a common complication of repeated vomiting or prolonged gastric suction. In the case we observed, a patient presented with chronic hypokalemia due to gastric dilatation and the development of a superior mesenteric artery syndrome several years after gastric banding. This paper presents pre-operative and post-operative illustrations of a rare but potentially serious entity.


High spatial resolution zonal wavefront reconstruction with improved initial value determination scheme for lateral shearing interferometry.
In a recent paper [J. Opt. Soc. Am. A 29, 2038 (2012)], we proposed a generalized high spatial resolution zonal wavefront reconstruction method for lateral shearing interferometry. The test wavefront can be reconstructed with high spatial resolution by using linear interpolation on a subgrid for initial values estimation. In the current paper, we utilize the difference between the Zernike polynomial fitting method and linear interpolation in determining the subgrid initial values. The validity of the proposed method is investigated through comparison with the previous high spatial resolution zonal method. Simulation results show that the proposed method is more accurate and more stable to shear ratios compared with the previous method. A comprehensive comparison of the properties of the proposed method, the previous high spatial resolution zonal method, and the modal method is performed.


Transfer of human chromosomes via human minisegregant cells into mouse cells and the quantitation of the expression of hypoxanthine phosphoribosyltransferase in the hybrids.
The behaviour of human cells arrested in mitosis can be severely perturbed so as to generate numerous small minisegregants containing very few chromosomes. These cells can be separated according to size and DNA content and fused with intact cells. In this paper we describe the production and some properties of proliferating cell hybrids generated by fusion of human minisegregant cells derived from a HeLa strain with mouse A9 cells deficient in hypoxanthine phosphoribosyltransferase (HPRT, EC 2.4.2.8). The hybrids were shown to contain up to 10 human chromosomes including a single X. Independently derived hybrid clones were quantitatively characterized and compared with the parental phenotypes with respect to HPRT. Human isozymes of each of the 3 enzymes HPRT, glucose-6-phosphate dehydrogenase (EC 1.1.1.49) and phosphoglycerate kinase (EC 2,7.2.3) were found. Tests to evaluate both structure and function of HPRT were utilized. The specific activity of HPRT of more than 10 hybrids tested was approximately 10% that of the HeLa parent. Structural characterization of HPRT from hybrid cells as evidenced by heat inactivation and electrophoretic mobility results in a 'human-like' phenotype. Functional characterization of parental HPRT results in kinetic constants for cofactor and substrate which do not permit distinction of human and of human and mouse enzymes; HPRT from the minisegregant hybrids had normal kinetic constants. The reduced specific activity of HPRT in the hybrids is discussed in terms of the inability of the mouse environment to regulate the full expression of the human structural gene.


Sub-Rayleigh optical vortex coronagraphy.
We introduce a new optical vortex coronagraph (OVC) method to determine the angular distance between two sources when the separation is sub-Rayleigh. We have found a direct relationship between the position of the minima and the source angular separation. A priori knowledge about the location of the two sources is not required. The superresolution capabilities of an OVC, equipped with an ℓ = 2 N-step spiral phase plate in its optical path, were investigated numerically. The results of these investigations show that a fraction of the light, increasing with N, from the secondary source can be detected with a sub-Rayleigh resolution of at least 0.1 λ/D.


Ovarian steroids reduced apoptotic death in SV40 temperature-sensitive mutant virus transformed uterine epithelial cells.
Ovarian steroids have been shown to inhibit uterine cell death in vivo. In this study, we investigated whether ovarian steroids regulated cell death in an uterine epithelial cell line transformed with SV40 temperature-sensitive (ts) mutant virus. To assess cell death rate, cells were grown at permissive temperature (34 degrees C) and pulsed with 3H-thymidine. The retention of incorporated radioactivity was then examined after a temperature shift to nonpermissive temperature (40 degrees C) in the absence or presence of estradiol and progesterone. When cells were continuously cultured at 34 degrees C, cell number increased rapidly and most of radioactivity was retained in the attached cells. However, the temperature shift from 34 degrees C to 40 degrees C resulted in a decrease in cell number and radioactivity in attached cells. Estradiol and progesterone attenuated this temperature shift-induced cell death. Morphological examination with Hoechst 33258 staining revealed that the temperature shift increased the percentage of apoptotic death. The treatment of ovarian steroids reduced the extent of apoptotic death. Our studies demonstrated that ovarian steroids could act directly on uterine epithelial cells to reduce apoptotic death in culture.


Optimized culture condition for enhancing lytic performance of waste activated sludge by Geobacillus sp. G1.
Hydrolysis is known as the rate-limiting step during waste activated sludge (WAS) digestion. The optimization of the culture conditions of Geobacillus sp. G1 for enhancing WAS hydrolysis was conducted in this study with uniform design and response surface methodology. Taking the lysis rate of Escherichia coli as the response, the Plackett-Burman design was used to screen the most important variables. Experimental results showed that the maximum predicted lysis rate of E. coli was 50.9% for 4 h treatment time with concentrations of skim milk, NaCl and NH4SO4 at 10.78, 4.36 and 11.28 g/L, respectively. The optimized dosage ratio of Geobacillus sp. G1 to WAS was 35%:65% (VG1:VWAS). Under this condition, soluble protein was increased to 695 mg chemical oxygen demand (COD)/L, which was 5.0 times higher than that obtained in the control (140 mg COD/L). The corresponding protease activity reached 1.1 Eu/mL. Scanning electron microscopy showed that abundant cells were apparently lysed with treatment of Geobacillus sp. G1.


[Clinical usefulness of troponin I in acute pulmonary embolism].
Troponin-I (cTp-I) is considered a sensitive biomarker of myocardial injury in acute pulmonary thromboembolism (PE) with prognosis implications, though abnormal levels vary among reports. cTp-I was measured in consecutive patients objectively diagnosed of PE by means of pulmonary angiography made with helicoidal CT. Patients were classified radiologically as central or peripheral PE and hemodynamically as massive, submassive or non-massive according to the pulmonary vessel occluded and systolic blood pressure and ProBNP levels respectively. We checked also the delay in diagnosis (DD) and 30-days all-causes mortality rate. We evaluated 164 patients; the mean age was 70 (15) years, males: 76 (46%). Median DD was 5 [interquartile range (IQ) 12) days. Median cTp-I in patients with DD>5 was 0.003microg/L (IQ 0.072)microg/L while in patients with DD<5 was 0.05microg/L (IQ 0.096) (p<0.05). cTp-I higher than 0.5microg/L occurred in 11 (7%) patients. Levels of cTp-I higher than 0.03microg/L were associated with central PE, (AUROC 0.7059 CI95% 0.6643-0.7475, sensitivity 0.75, specificity 0.69, PPV 0.75 and NPV 0.69) and massive and submassive PE (AUROC 0.7685, CI95% 0.7288-0.8082 sensitivity 0.86, specificity 0.66, PPV 0.72 and NPV 0.82), but they were not associated with mortality (AUROC 0.5394). In a multivariate analysis cTp-I did not show to be an independent predictor of central, massive and submassive PE or all causes death. In this study cTp-I was not a proper biomarker of the size of pulmonary vessel occluded, the degree of hemodynamic derangement or short-term mortality. The delay in diagnosis could influence the usefulness of cTp-I.


Angiogenesis and inflammation signaling are targets of beer polyphenols on vascular cells.
Emerging evidence indicates that chronic inflammation and oxidative stress cluster together with angiogenic imbalance in a wide range of pathologies. In general, natural polyphenols present health-protective properties, which are likely attributed to their effect on oxidative stress and inflammation. Hops used in beer production are a source of polyphenols such as xanthohumol (XN), and its metabolites isoxanthohumol (IXN) and phytoestrogen 8-prenylnaringenin (8PN). Our study aimed to evaluate XN, IXN, and 8PN effects on angiogenesis and inflammation processes. Opposite in vitro effects were observed between 8PN, stimulating endothelial and smooth muscle cell (SMC) growth, motility, invasion and capillary-like structures formation, and XN and IXN, which inhibited them. Mouse matrigel plug and rat skin wound-healing assays confirmed that XN and IXN treatments reduced vessel number as well as serum macrophage enzymatic activity, whereas 8PN increased blood vessels formation in both assays and enzyme activity in the wound-healing assay. A similar profile was found for serum inflammatory interleukin-1β quantification, in the wound-healing assay. Our data indicate that whereas 8PN stimulates angiogenesis, XN and IXN manifested anti-angiogenic and anti-inflammatory effects in identical conditions. These findings suggest that the effects observed for individual compounds on vascular wall cells must be carefully taken into account, as these polyphenols are metabolized after in vivo administration. The modulation of SMC proliferation and migration is also of special relevance, given the role of these cells in many pathological conditions. Furthermore, these results may provide clues for developing useful therapeutic agents against inflammation- and angiogenesis-associated pathologies.


Practical modelling of monopolar axonal stimulation.
Three models describing monopolar electrical stimulation of unmyelinated axons in large, uniformly conducting volumes are presented. The first is a representation of the axon as a continuous and straight electric cable of finite length with sealed ends. It has a power-series solution for the steady state which after truncation beyond the fifth term provides an accurate reflection of the imposed membrane potential for all parts of the axon except, under certain conditions, near terminals and directly opposite a closely apposed electrode. At these points, the inclusion of higher-order terms improves the accuracy quite slowly--11 terms are sometimes still unsatisfactory. The second is a steady-state solution, in terms of higher transcendental functions, for the point opposite the stimulating electrode in a similar but infinitely long cable. This turns out to be practical for estimating the membrane potential at the site of cathodal excitation under the majority of realistic geometrical and electrical parameters, and consequently complements the first method. It may be calculated with ease from mathematical tables. The third, a simulation of the cable by means of discrete electrical components (compartments), can give the complete distribution of membrane potential as a function of time with potentially unlimited accuracy. However, it takes special computer programs to set up and solve either the steady-state determinant or, if transients are desired, the time-dependent differential equation. Calculation of the voltage distribution with one of the analytical methods will often be faster for a reasonable level of accuracy, since their algorithms are independent of the total number of points introduced.


An appraisal of the interrelationships between prostaglandins and cyclic nucleotides in inflammation.
The evidence supporting the role of prostaglandins and cyclic nucleotides "in vitro" has been reviewed. The pro-inflammatory role of prostaglandins of the E series (PGE) is typified by its ability to induce increased vascular permeability. Prostaglandins of the F series (PGF) may be anti-inflammatory via their inhibitory effect on increased vascular permeability. However, a paradox exists which suggests that PGE may also be anti-inflammatory via its stimulatory effect on cyclic AMP synthesis as shown "in vitro" (e.g. decreased leucocyte lysosomal enzyme secretion; decreased lymphocyte cytotoxicity and mitosis; decreased release of mediators from sensitized tissues during anaphylaxis). Conversely PGF is capable of stimulating cyclic GMP which augments the processes listed above, and may therefore be termed pro-inflammatory. An attempt has been made to correlate these findings with "in vivo" studies which support the anti-inflammatory role of cyclic GMP. However, the significance of PGE and PGF in the inflammatory response "in vivo" appears to be more complex. It is suggested that greater emphasis should be placed on the "in vivo" study of beta-adrenergic and cholinergic mediators, substances which induce the anti- and pro-inflammatory effects of cyclic AMP and cyclic GMP "in vitro", respectively.


Recent developments in HMO malpractice liability: Chase v. Independent Practice Association.
The court's decision in Chase demonstrates that an HMO or independent practice association need not incur liability for the negligence of a physician if the arrangement between the entity and the physicians who provide services on its behalf is properly structured and maintained. IPA's successful defense of this lawsuit was based upon: (1) careful structuring of an independent relationship with the medical group, including appropriate wording in the contract establishing the relationship; and (2) careful maintenance of the relationship consistent with the terms of the contract to avoid giving patients any reason to believe that an agency relationship existed.


Diagnosing schistosomiasis.
The ideal diagnostic method for schistosomiasis detection seems to be still far from available. Paucity of egg output in low prevalence situations, low levels of circulating antigens in individuals with low intensity of infection and inadequate specificity of antibody detection systems outline pieces of a puzzle that challenges scientific efforts. Estimated prevalence, financial resources and operational reality must be taken into account when deciding the diagnostic method to be used. A combination of a screening step, using a fast strip test for antibody detection with a parasitological ratification step such as Kato-Katz repeated stool examination may serve as a diagnostic approach for a previously untreated low level endemic area. However, when eradication is the aim, and high financial investment is available, re-treatment may be based on the association between multiple stool examination and circulating antigen detection. Ethical aspects as well as cost-benefit rates between treatment and diagnosis approaches lead to the conclusion that in spite of the recent advances in simple administered and relatively safe drugs, treatment should only be performed when supported by appropriated diagnosis.


Stimulatory effect of D-ephedrine on beta3-adrenoceptors in adipose tissue of rats.
The effect of ephedrine on beta3-adrenoceptos (beta3-AR) was studied in the isolated adipose tissue of Wistar rat. Incubation with D-ephedrine (0.1-10 microM) induced a concentration-dependent decrease of uptake of [14C]-deoxy-D-glucose into white adipose tissues (WAT). The inhibitory effect of D-ephedrine was potentiated by BRL 37344, the agonist of beta3-AR and concentration-dependently inhibited by SR 59230A, the selective antagonist of beta3-AR. The action of D-ephedrine on beta3-AR was further blocked by the antibodies for beta3-AR, but not the immunoglobulin. in a concentration-dependent manner. Moreover, D-ephedrine increased glycerol release from the isolated brown adipose tissues (BAT) and this action was also abolished by SR 59230A at concentration sufficient to block beta3-AR. Thus, these results suggest that D-ephedrine has the ability to activate beta3-AR both in WAT and BAT of Wistar rats in vitro.


Abortion training in three family medicine programs: resident and patient outcomes.
Three family medicine residency programs in California integrated abortion training into routine gynecology rotations in academic years 2003-2004 and 2004-2005. Forty-six (88%) of 52 eligible residents participated in the abortion training sessions. Of these 46 residents, 39 (85%) chose to perform abortion procedures, and seven residents elected to provide other aspects of patient care only. Resident evaluations of the training program were overwhelmingly positive. Moreover, two thirds of the 43 post-training survey respondents reported that the training program increased their interest in providing abortion services, and no resident reported decreased interest. The resident complication rate was 1.0%. In post-procedure surveys completed by 155 patients at two training sites, patients reported a high level of satisfaction with the care they received from the training team. These program evaluation results suggest that abortion training can safely be integrated into family medicine residency programs, with a positive reception by both residents and patients.


A novel thiol compound, N-acetylcysteine amide, attenuates allergic airway disease by regulating activation of NF-kappaB and hypoxia-inducible factor-1alpha.
Reactive oxygen species (ROS) play an important role in the pathogenesis of airway inflammation and hyperresponsiveness. Recent studies have demonstrated that antioxidants are able to reduce airway inflammation and hyperreactivity in animal models of allergic airway disease. A newly developed antioxidant, small molecular weight thiol compound, N-acetylcysteine amide (AD4) has been shown to increase cellular levels of glutathione and to attenuate oxidative stress related disorders such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. However, the effects of AD4 on allergic airway disease such as asthma are unknown. We used ovalbumin (OVA)-inhaled mice to evaluate the role of AD4 in allergic airway disease. In this study with OVA-inhaled mice, the increased ROS generation, the increased levels of Th2 cytokines and VEGF, the increased vascular permeability, the increased mucus production, and the increased airway resistance in the lungs were significantly reduced by the administration of AD4. We also found that the administration of AD4 decreased the increases of the NF-kappaB and hypoxia-inducible factor-1alpha (HIF-1alpha) levels in nuclear protein extracts of lung tissues after OVA inhalation. These results suggest that AD4 attenuates airway inflammation and hyperresponsiveness by regulating activation of NF-kappaB and HIF-1alpha as well as reducing ROS generation in allergic airway disease.


[A survey of mental health among transferred injured survivors in Wenchuan earthquake in Sichuan].
To assess the depression and anxious status among transferred injured survivors in Wenchuan earthquake in Sichuan province. A total of 43 transferred injured survivors were investigated by questionnaire exploring their trauma symptoms and mental health status. High rates of trauma symptoms were remarkably observed in these survivors. Of all the respondents, 60% had some emotional symptoms and sleeping difficulties. About one third of respondents experienced recurrent and intrusive distressing recollection of event, 16 (37.21%) experienced nightmare, 15 (34.88%) had flashback and 7 (16.28%) of them tried to avoid relative stress. Many mental symptoms were observed in transferred injured survivors. The two major factors of mental stress were emotional symptoms and re-experience of the disaster.


A computing platform to support communication and sense-making in intensive care.
We developed a conceptual design of a mobile computing platform to support multi-disciplinary rounds in intensive care units.


Binding sites for progastrin-derived peptides in colonic crypts.
Gastrin17gly acts as a growth factor for the colonic mucosa. Studies on the binding properties of the receptor involved in transducing the proliferative effects have generally been confined to colorectal carcinoma cell lines, and no investigation of gastrin17gly receptors on normal colonocytes has yet been reported. The aim of this study was to investigate the binding of 125I-[Met15]-gastrin17gly to normal colonic crypts. Crypts were released from normal rat and rabbit colonic mucosa by treatment with EDTA and isolated by centrifugation. The binding of 125I-[Met15]-gastrin17gly was measured in displacement experiments with increasing concentrations of either gastrin17gly, gastrin17 or gastrin receptor antagonists. The concentrations required for 50% inhibition were determined by the use of curve fitting. 125I-[Met15]-Gastrin17gly bound to both rat and rabbit crypts, and displacement experiments with unlabeled gastrin17gly revealed that the IC50 values were 1.0 +/- 0.6 and 0.6 +/- 0.2 micromol/L, respectively. Binding was also competed by gastrin17, with IC50 values of 2.4 +/- 1.7 and 2.4 +/- 0.7 micromol/L, respectively. Binding was inhibited by the non-selective gastrin/CCK receptor antagonists proglumide and benzotript, but not by the cholecystokinin (CCK)-A receptor antagonist L364 718, or the gastrin/CCK-B receptor antagonist L365 260. We conclude that the gastrin17gly binding site on normal colonic crypts has properties consistent with the gastrin/CCK-C receptor.


Immediate appendectomy for appendiceal mass.
The aim of this retrospective study was to evaluate the safety and effectiveness of immediate appendectomy in patients presenting with appendicular mass. Forty-seven patients with appendicular mass were operated within 24 hours after admission to Vakif Gureba Training and Research Hospital, General Surgery Department, from January 2004 to April 2010. The appendiceal mass was diagnosed with physical examination, abdominal ultrasonography, and computed tomography, or during surgical exploration. Age and sex, duration of symptoms, physical examination findings at admission, operation details, intraoperative and postoperative complications, and length of hospital stay were analyzed for each patient. There were 25 males (53.2%) and 22 females (46.8%), with a mean age of 37.23±15.60 (range: 14-75) years. The mean time from the onset of the symptoms to operation was 4.06±2.50 (range: 1-15) days. A simple appendectomy was performed in 38 (80.9%) patients. Twenty-nine (61.8%) patients were discharged and followed up without any complication after surgery. Wound infection was detected in 13 (27.7%) patients. Immediate appendectomy in appendicular mass is a safe and effective alternative to conservative management.


Isolation and characterization of Aujeszky's disease virus in captive brown bears from Italy.
An epizootic of Aujeszky's disease (pseudorabies) in four captive European brown bears (Ursus arctos) in November 1994, in the Val di Non, Trentino Region, Italy, was linked to consumption of raw pork. Affected animals had severe pruritus resulting in self-mutilation, and all four died within 24 hr after onset of clinical signs. Aujeszky's disease virus was isolated on first passage from the brain and was characterized by means of restriction endonuclease analysis. Based on these data, we believe that bears are extremely susceptible to the disease, and that wildlife managers should consider pseudorabies as a potential risk for the captive and wild bear populations.


Zinc status does not affect aluminum deposition in tissues of rats.
To examine whether zinc deficiency would increase the toxicity of dietary aluminum, weanling, male Sprague-Dawley rats were fed purified diets containing either 2 or 30 mg Zn/kg diet, with or without 500 mg Al/kg diet for 28 d. Individually pair-fed rats were fed the 30 mg Zn/kg diet with or without added aluminum to control for inanition secondary to zinc deficiency. Rats fed the 2 micrograms Zn/kg diet showed evidence of zinc deficiency, including anorexia, growth retardation, and depressed concentrations of zinc in tibias and livers. Zinc deficiency did not significantly increase the concentrations of aluminum in the tibias, livers, kidneys, or regions of the brain examined (cerebrum, cerebellum, midbrain, and hippocampus). Inclusion of aluminum in the diet did not alter aluminum concentrations in the various tissues. Under the conditions of this study, zinc deficiency did not result in greater sensitivity to dietary aluminum exposure.


Impact of cochlear nerve deficiency determined using 3-dimensional magnetic resonance imaging on hearing outcome in children with cochlear implants.
1) To review the radiologic and audiologic data of 656 children with sensorineural hearing impairment who underwent 3-dimensional magnetic resonance imaging (MRI) in our cochlear implant (CI) center to understand the incidence of cochlear nerve deficiency (CND); and 2) to compare postimplant auditory and speech intelligibility outcomes in implantees with cochlear nerve (CN) aplasia, CN hypoplasia, and normal CN. A retrospective cohort study. A tertiary medical center. A total of 656 patients (aged 0-18 yr; mean, 4.5 ± 4.3 yr) who underwent MRI in our center during May 2000 to December 2012. The radiologic/audiologic data were reviewed. The postimplant outcomes of 13 implantees with CND (7 aplasia and 6 hypoplasia) were compared with 50 non-CND implantees using the Categories of Auditory Performance (CAP) and the Speech Intelligibility Rating (SIR) scales. Upon MRI, 139 patients (21.2%) exhibited CND. Bilateral CN aplasia occurred in 4.3% of the patients with severe-to-profound deafness (588 cases) and in one-fifth of patients with CND. The aplasia group showed significantly worse postimplant CAP (p = 0.002) and SIR (p = 0.009) scores than the non-CND group. No significant difference was noted between the hypoplasia group and the non-CND group. Although the audiologic and radiologic results may be incompatible, the majority of patients with CND may be well delineated preoperatively using MRI. The type of CND (aplasia/hypoplasia) may affect CI outcomes. Patients implanted on the side with CN hypoplasia are more likely to exhibit favorable results compared with patients implanted on the side with CN aplasia.


Suppression of amber nonsense mutations of herpes simplex virus type 1 in a tissue culture system.
We have investigated the ability of monkey kidney cell lines (SupD3 and SupD12) inducibly expressing an amber suppressor tRNA(ser) to suppress amber nonsense mutations in three genes of herpes simplex virus type 1 (HSV-1). HSV-1 mutant TK4, which contains a nonsense mutation in the non-essential viral thymidine kinase (TK) gene, synthesized a full-length TK polypeptide at about 30% of the wild-type (wt) level in induced SupD3 cells but not in the parental non-suppressor (Sup0) cells. Using complementing cells, we constructed HSV-1 mutants carrying nonsense mutations in an essential gene, UL8, encoding a protein essential for viral DNA replication (ambUL8) or in a partially dispensable gene, UL12, encoding alkaline nuclease (ambUL12). The growth of the mutants in Vero or Sup0 cells was either totally (ambUL8) or severely (ambUL12) impaired, whereas in cells expressing suppressor tRNA the mutants produced infectious virus. However, the yields were much lower than obtained with wt HSV-1. In Vero or Sup0 cells the mutants ambUL8 and ambUL12 failed to synthesize full-length UL8 and UL12 protein products, respectively. Western immunoblotting showed that the virus ambUL12 produced full-length UL12 protein in SupD12 cells which yielded a level of 25.9% of the alkaline nuclease activity of the wt HSV-1 control. Our results show that the levels of suppression of the nonsense mutations in ambUL8 and ambUL12 are insufficient to allow their continuing propagation in the available Sup+ cells. Possible reasons are discussed.


Enzyme-linked immunosorbent assay of ochratoxin A in wheat.
An enzyme-linked immunosorbent assay (ELISA) was developed for the quantitation of ochratoxin A amended to wheat. Ochratoxin A conjugated to horseradish peroxidase (HRP) was used as an enzyme marker in the assay. At toxin levels below 30 ppb, a cleanup treatment was necessary for ELISA. Among 3 cleanup methods tested (solvent partition, Sep-Pak cartridge treatment, solvent partition and cartridge treatment), reverse phase cartridge treatment was the most simple and effective. In the analysis, ochratoxin A was extracted from wheat with methanol. The methanolic extract was diluted with water to a final 10-15% methanol content, and then passed through a cartridge. Ochratoxin A was eluted from the cartridge with 85% methanol which was then concentrated. The final solution, in 0.1M, pH 7.5 sodium phosphate-Tween 20 buffer and 5% methanol, was then subjected to ELISA. ELISA allowed minimal detection of the toxin in wheat at the 1-2 ppb level after cleanup. Recoveries of toxin added to wheat samples in the 1.0-30 ppb range were 85-90% with standard deviations of 10-15%.


Random approach to determine the broadening of intersubband and interband transitions in (In)GaN/Al(In)N quantum wells.
A random approach to determine the broadening of intersubband (IS) and interband (IB) transitions in (In)GaN/Al(In)N quantum wells (QWs) has been proposed in this work. Within this approach, energies and intensities of IS and IB transitions have been calculated for 1000 randomly generated QWs with Gaussian distribution of QW width, barrier width, and indium concentration. From the results of these calculation a histogram of the intensity of optical transitions has been built. In this paper the influence of each parameter (QW width, barrier width, and indium content) on the broadening of IS and IB transitions has been considered independently and then all of the parameters have been taken into account at the same time. The obtained broadenings of IS and IB transitions have been compared with the available experimental data. It has been clearly shown that the large broadening of IS and IB transitions in the (In)GaN/Al(In)N multi-quantum well system results from the statistical distribution of QW sizes and indium concentration.


In-situ characterization of the bacterial biofilm associated with Xeroform™ and Kaltostat™ dressings and evaluation of their effectiveness on thin skin engraftment donor sites in burn patients.
Biofilm forms when bacteria surrounded by an extracellular matrix aggregate on a surface. It can develop on many surfaces, including wound dressings; this can be particularly nefarious for burn patients undergoing skin grafting (autograft) for burn wound coverage as they often suffer from compromised immune system function. Autograft donor sites are particularly vulnerable to biofilm formation; as such, timely healing of these sites is essential. Our aim was to apply scanning electron microscopy to compare the efficacy of two types of wound dressings in preventing the formation of bacterial biofilm on burn patient skin graft donor sites. One dressing contained bismuth tribromophenate at a concentration of 3% which confers it bacteriostatic properties (Xeroform™). The other was an absorptive alginate calcium sodium dressing (Kaltostat™). Samples of each wound dressing, which were in contact with the skin graft donor site, were prepared for analysis under the scanning electron microscope (SEM) using an original method developed by our research group that aims to maintain the integrity of the biofilm microstructure. Samples prepared by this method were then analyzed using SEM, which allowed the characterization of biofilm and the evaluation of bacterial density on the studied dressing samples. To this day, this imaging technique has been rarely employed for dressing analysis and this is the first time that it is employed for in situ biofilm visualization for this particular application.


Selective and nonselective inverse agonists for constitutively active type-1 parathyroid hormone receptors: evidence for altered receptor conformations.
The spontaneous signaling activity of some G protein-coupled receptors and the capacity of certain ligands (inverse agonists) to inhibit such constitutive activity are poorly understood phenomena. We investigated these processes for several analogs of PTH-related peptide (PTHrP) and the constitutively active human PTH/PTHrP receptors (hP1Rcs) hP1Rc-H223R and hP1Rc-T410P. The N-terminally truncated antagonist PTHrP(5-36) functioned as a weak partial/neutral agonist with both mutant receptors but was converted to an inverse agonist for both receptors by the combined substitution of Leu(11) and D-Trp(12). The N-terminally intact analog [Bpa(2)]PTHrP(1-36)-a partial agonist with the wild-type hP1Rc-was a selective inverse agonist, in that it depressed basal cAMP signaling by hP1Rc-H223R but enhanced signaling by hP1Rc-T410P. The ability of [Bpa(2)]PTHrP(1-36) to discriminate between the two receptor mutants suggested that H223R and T410P confer constitutive receptor activity by inducing distinct conformational changes. This hypothesis was confirmed by the observations that: 1) the double mutant receptor hP1Rc-H223R/T410P exhibited basal cAMP levels that were 2-fold higher than those of either single mutant; and 2) hP1Rc-H223R and hP1Rc-T410P internalized (125)I-PTHrP(5-36) to markedly different extents. The overall results thus reveal that two different types of inverse agonists are possible for PTHrP ligands (nonselective and selective) and that constitutively active PTH-1 receptors can access different conformational states.


Prognostic value of stress Tc-99m tetrofosmin SPECT in patients with previous myocardial infarction: impact of scintigraphic extent of coronary artery disease.
Our objective was to assess the prognostic value of the scintigraphic extent of coronary artery disease on stress technetium 99m tetrofosmin single photon emission computed tomography in patients with previous myocardial infarction. We studied 383 patients (280 men and 103 women; mean age, 60 +/- 11 years) more than 3 months after an acute myocardial infarction by exercise bicycle or dobutamine (up to 40 mug . kg -1 . min -1 ) stress Tc-99m tetrofosmin myocardial perfusion tomography. Stress images were acquired 1 hour after stress, and rest images were acquired 24 hours after stress testing. An abnormal study was defined as one demonstrating a reversible or fixed perfusion abnormality. Myocardial segments were assigned to corresponding coronary arteries as follows: the apex, anterior wall, and anterior septum were assigned to the left anterior descending coronary artery; the posterolateral wall was assigned to the left circumflex artery; and the basal posterior septum and inferior wall were assigned to the right coronary artery. During a mean follow-up of 4.3 +/- 2.1 years, 48 cardiac events occurred (36 cardiac deaths and 12 nonfatal myocardial infarctions). Myocardial perfusion was normal in 51 patients, abnormal in a single-vessel distribution in 170 patients, and abnormal in a multivessel distribution in 162 patients. The annual cardiac event rates in these groups were 0.4%, 2.6%, and 4%, respectively. In a multivariate analysis model, independent predictors of cardiac events were diabetes mellitus (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.4-4.5), history of congestive heart failure (OR, 2.7; 95% CI, 1.4-4), age (OR, 1.05; 95% CI, 1.01-1.08), and scintigraphic extent of coronary artery disease (OR, 4.2; 95% CI, 1.8-9.1). Stress Tc-99m tetrofosmin myocardial perfusion imaging provides independent prognostic information for the risk stratification of patients with previous myocardial infarction. The event rate is directly related to the scintigraphic extent of coronary artery disease. Patients with normal perfusion have an excellent event-free survival rate.


A practical, cost-effective, noninvasive system for cardiac output and hemodynamic analysis.
Impedance cardiography is a relatively inexpensive, noninvasive technique for measuring cardiac output on the basis of resistive changes in the thorax to electrical current flow. In conjunction with blood pressure monitoring and physiologic maneuvers, the technique may be used to monitor thoracic and total body fluid volume and express a variety of contractility indexes as well as relative and absolute measurements of stroke volume. We have tested hemodynamics in our laboratory by using a cost-effective, powerful microcomputer-based portable noninvasive technique, which makes possible the ensemble averaging of impedance cardiographic waveforms. In conjunction with physiologic maneuvers, the technique has been implemented at our institution and has provided helpful information in our experience in evaluating volume overload, hypertension, hypotension, shock, and heart failure. It is hoped that this noninvasive, relatively cost-effective approach will be more widely appreciated in the future, given the economic realities of medicine today.


Influence of single-trial results on clinical practice: example of adenotonsillectomy in children.
To establish whether the results of a 2004 trial on the effectiveness of adenotonsillectomy in children with mild to moderate symptoms of throat infection or adenotonsillar hypertrophy affected physicians' beliefs about the benefits of the operation and influenced clinical practice. Prospective prior-posterior study. Academic research. We evaluated beliefs prior and posterior to the 2004 trial regarding the benefits of adenotonsillectomy in a random sample of 120 Dutch otolaryngologists and 120 Dutch general practitioners. Physicians were asked to give their estimates of the probability of recovery during 1 year after adenotonsillectomy or a nonsurgical strategy in 3 scenarios of children aged 3 to 4 years with recurrent throat infection, upper respiratory tract infection (with or without fever), or sleep-related breathing disorder. Ninety-four percent of otolaryngologists (n = 46) and 31% of general practitioners (n = 14) were familiar with the 2004 trial results. Posterior beliefs of otolaryngologists and general practitioners did not differ substantially from prior beliefs; overall expectations regarding the benefits of adenotonsillectomy remained high. Dissemination of the 2004 trial results did not seem to affect the beliefs of physicians regarding the benefits of adenotonsillectomy. isrctn.org Identifier: ISRCTN04973569.


Growth hormone deficiency after traumatic brain injury in adults: when to test and how to treat?
Hypopituitarism has numerous potential causes, and it is becoming clear that traumatic brain injury (TBI), including traffic accidents and sport-related injuries, is commonly associated with pituitary dysfunction. Mechanisms of pituitary damage after TBI include direct injury and vascular problems, and more recent research suggests that autoimmunity may also be involved. There may also be a genetic influence, as the E3 allele of the ApoE gene may provide some protection from post-traumatic hypopituitarism. Studies suggest that patients with mild or moderate TBI are likely to recover pituitary function over time. In patients with severe TBI, however, adrenocorticotrophic hormone and growth hormone deficiencies may persist. Patients who experience TBI should, therefore, be followed up carefully and evaluated for pituitary dysfunction to ensure that appropriate hormone replacement therapy can be provided if needed.


[Studies on the active polysaccharides from Lycium barbarum L].
To investigate the structures and immunomodulation activity of four homogeneous polysaccharides: LBP 1a-1, LBP 1a-2, LBP 3a-1 and LBP 3a-2 isolated from Lycium barbarum L. brought from Zhongning County, Ningxia Province. Their molecular weights, sugar component (constituents) and their linkages were determined by gel permeation chromatography, acid hydrolysis, periodate oxidation and NMR spectrum. The activity of immunomodulation was evaluated with splenocyte proliferation by [3H]-TDR incorperation, in vitro. Four polysaccharides with molecular weights 11.5 x 10(4), 9.4 x 10(4), 10.3 x 10(4) and 8.2 x 10(4), were shown to enhance splenocyte proliferation induced by ConA. LBP 1a-1 and LBP 1a-2 were alpha-(1-->6)-D-glucans. LBP 3a-1 and LBP 3a-2 were found to be a-(1-->4)-D-polygalacturonans. The four polysaccharides were first isolated from this plant. Polysaccharides with main chain of alpha-(1-->4)-D-polygalacturonans showed stronger immunomodulation activity.


The O-specific polysaccharide from the marine bacterium Pseudoalteromonas agarivorans KMM 255(T).
The O-specific polysaccharide was isolated from the lipopolysaccharide of a marine bacterium Pseudoalteromonas agarivorans KMM 255(T) and studied by chemical methods along with (1)H and (13)C NMR spectroscopies. The following new structure of the O-specific polysaccharide from P. agarivorans KMM 255(T) containing 2-acetamido-2-deoxy-D-glucose (D-GlcNAc), D-glucose (D-Glc), D-glucuronic acid (D-GlcA) and two residues of D-galactose (D-Gal) was established: Formula: see text].


Formulation and biopharmaceutical evaluation of a transdermal patch containing aceclofenac.
To reduce the adverse effects of aceclofenac that accompanied with oral administration of this drug, transdermal patches in the form of drug-in-adhesive (DIA) patches, containing aceclofenac, were formulated. The effect of formulation factors on the skin permeation of the drug and physical properties of the patch were evaluated using excised rat skins. The optimized patch contained 12 % aceclofenac and 20 % lauryl alcohol in DT-2852 as a pressure-sensitive adhesive. The pharmacokinetic characteristics of the DIA patch were determined after application of the transdermal patches to human volunteers. The calculated relative bioavailability of the aceclofenac DIA patch was 18.2 % compared to oral administration of the drug. The findings of this study suggest that transdermal application of aceclofenac can substitute for oral administration of the drug.


The relationship of psychological-mindedness to adult perceptions of early parental rejection.
We tested the hypothesis that highly psychologically minded individuals perceive having grown up with rejecting parents. A Psychological Mindedness (PM) Scale, and the Parent-Child Relations Questionnaire II (PCR), were administered to 120 college students. Contrary to prediction, a significant negative correlation was found between PM and perceptions of early maternal rejection. Psychological-mindedness, it was suggested, may be attributable to "good enough mothering" and may be learned through modeling and imitation of mothers' empathic perceptions, affective responses, and behavior.