Caste-specific tyramides from Myrmicine ants.
Analysis of the extracts of male ants of Monomorium minimum and Monomorium ebeninum by GC-MS and GC-FTIR revealed the presence of tyramides 2 and 4c, for which the structures were established by comparison with synthetic samples. These compounds and their analogues 1 and 3 were also found in males of other Monomorium species, males of Myrmicaria opaciventris, and males of several Solenopsis (Diplorhoptrum) species. Vapor-phase FTIR spectra revealed critically important structural clues to two of the tyramides, which had methyl branching in the tyramide acyl moiety. Tyramide 4c exhibited a strong intramolecular amide NH hydrogen bond where an alpha-keto group was deduced to be present in the acyl moiety and also showed the overlap of this ketone group frequency with that of the amide nu(C horizontal lineO). The biological function of these compounds is uncertain; however, their role in ant-mating behavior may be suggested by a large body of evidence.


General and practical conversion of aldehydes to homologated carboxylic acids.
The reaction of aldehydes with trichloromethide followed by sodium borohydride or sodium phenylseleno(triethyl)borate under basic conditions affords homologated carboxylic acids in high yields. This operationally simple procedure provides a practical, efficient alternative to other homologation protocols. The approach is compatible with sensitive aldehydes including enals and enolizable aldehydes. It also offers convenient access to alpha-monodeuterated carboxylic acids.


Langerhans cell histiocytosis: report of a single organ involvement in a child.
Langerhans cell histiocytosis is a rare disorder characterized by abnormal proliferation of Langerhans cells that can affect various organ systems. The disease usually presents as a unifocal lytic bone lesion and can affect any age group. Less frequently it presents as a disseminated disease with multisystem involvement. Hepatic manifestation in Langerhans cell histiocytosis is relatively rare and usually presents as a part of a disseminated process. We report a case of Langerhans cell histiocytosis involving only the liver in a 9-years-old child.


Tivozanib for the treatment of renal cell carcinoma: results and implications of the TIVO-1 trial.
Multiple VEGF and mTOR inhibitors have provided improvements in median progression-free survival for metastatic renal cell carcinoma. Tivozanib is a potent and specific VEGFR-1, -2 and -3 tyrosine kinase inhibitor. Promising results led to the TIVO-I Phase III trial (n = 517) comparing tivozanib with sorafenib in patients who were either untreated or had received cytokines. This study met its primary end point by statistically significantly improving progression-free survival, but did impair overall survival, a secondary end point. Crossover from sorafenib to tivozanib may have confounded survival. Because of that detrimental survival, the US FDA rejected approval in May 2013, leading to interruption in its development for renal cell carcinoma.


Associations of maternal pre-pregnancy obesity and excess pregnancy weight gains with adverse pregnancy outcomes and length of hospital stay.
It is relatively less known whether pre-pregnancy obesity and excess gestational weight gain (GWG) are associated with caesarean delivery, pregnancy complications, preterm birth, birth and placenta weights and increased length of postnatal hospital stay. We used a population-based cohort of 6632 women who gave birth in Brisbane, Australia, between 1981 and 1983. The independent associations of pre-pregnancy obesity, GWG and institute of medicine (IOM) categories of combined pre-pregnancy BMI and GWG with outcomes were examined using multivariable regression (for continuous outcomes) and multivariable multinomial regression (for categorical outcomes) models. We found women who were obese prior to pregnancy and women who gained excess weight during pregnancy were at greater risk for a pregnancy complications (OR: 2.10; 1.74, 2.54; age adjusted model), caesarean section (OR 1.29; 1.09, 1.54), higher birth weight difference (206.45 gm; 178.82, 234.08) and greater placental weight difference (41.16 gm; 33.83, 48.49) and longer length of hospital stay. We also found that mothers who gained inadequate weight or were underweight before pregnancy were at greater risk of preterm birth (2.27; 1.71, 3.00), lower risk of pregnancy complications (0.58; 0.44, 0.77) and had lower birth (-190.63;-221.05,-160.20) and placental (-37.16; -45.23,-29.09) weights. Results indicate that all associations remain consistent after adjustment for a range of potential confounding factors with the exception of the association between pre-pregnancy obesity and hospital stay. Pre-pregnancy obesity or excessive GWG are associated with greater risk of pregnancy complications, caesarean delivery and greater birth and placenta weight. Excess GWG is associated with a longer stay in hospital after delivery, independent of pre-pregnancy BMI, pregnancy complications and caesarean delivery. In addition to pre-pregnancy obesity, it is vital that clinical practice considers excess GWG as another indicator of adverse pregnancy outcomes.


Accumulation of radioisotopes with tumor affinity. II. Comparison of the tumor accumulation of 67Ga-citrate and 201Tl-chloride in vitro.
The kinetics in tumor cells and various factors affecting the tumor accumulation of 67Ga-citrate and 201Tl-chloride were studied in vitro. 67Ga was taken up gradually by tumor cells and its excretion from the cells decreased with time. 201Tl was taken up rapidly by tumor cells. Its excretion was very rapid, indicating that the two nuclides had entirely different kinetics in tumor cells. The uptake of 201Tl by culture cells correlated with that of 42KCl and was inhibited by Ouabain. 201Tl was hardly taken up by nonviable tumor cells. These facts indicate that active transport involving Na-K ATPase is involved in the tumor accumulation of 201Tl. The uptake of 67Ga and 201Tl by tumor cells was not affected by the administration of anticancer agents. The uptake of 67Ga by tumor cells was dependent upon the concentration of transferrin in the medium, which apparently plays a role as one of the pathways of tumor accumulation of 67Ga.


Temporal Stability of Self-Reported Trauma Exposure on the Life Events Checklist for DSM-5.
The Life Events Checklist for DSM-5 (LEC-5) is a comprehensive screening instrument used to detect exposure to a range of potentially traumatic events. Despite its widespread use, research assessing the psychometric properties of scores on the LEC-5-and trauma exposure more broadly-is scarce. Using a large sample of undergraduate students (N = 1,013), we sought to evaluate the reliability of trauma exposure reporting on the LEC-5 across 8- (N = 379) and 12-week (N = 343) intervals. Reliability estimates were examined for trauma exposure type (e.g., experiencing, witnessing), traumatic event type (e.g., sexual assault), and index trauma (i.e., "worst event") reporting. Reliability was more stable for events that were directly experienced, intraclass correlation coefficients (ICCs) = .62-64, than events that were witnessed, ICCs = .47-.52, or learned about, ICCs = .48-.53. Test-retest agreement was fair to good for reports of sexual assault, physical assault, transportation accidents, natural disasters, and other sexual experiences, κs = .49-.72, but only when individuals directly experienced these events. By contrast, across both assessment intervals, the agreement was attenuated, all κs < .40, for events that individuals witnessed or learned about regardless of event type. For index events, only sexual assault and sudden accidental or violent deaths were consistently reported with a fair or better agreement, κs = .42-.64. These findings suggest that reliable trauma reporting varies largely based on the nature of the traumatic event, yielding important implications for the assessment of DSM-5 Criterion A and posttraumatic stress disorder.


Fungal Olecranon Bursitis in an Immunocompetent Patient by Knoxdaviesia dimorphospora sp. nov.: Case Report and Review.
Bursitis is a common medical condition that can occur either with or without infection. We present a case of fungal olecranon bursitis in an immunocompetent individual caused by the new species Knoxdaviesia dimorphospora. It is a dematiaceous filamentous fungus characterized by the production of two different conidia: hyaline and cylindrical, which rise up from phialidic conidiogenous cells located in the upper part of differentiated and unbranched conidiophores, and pale brown and ellipsoidal conidia produced by phialidic conidiogenous cells which are born directly on hyphae. In addition to its morphological peculiarities, the novelty of the fungus was confirmed by sequence analysis of the internal transcribed spacer (ITS) regions and D1/D2 domains of the 28S of the nuclear rRNA gene. The fungal infection was confirmed by cytological examination and repeated cultures. The infection was resolved by surgical debridement and drainage, and the patient presented a complete functional recovery 3 months later. The in vitro antifungal susceptibility to this new human opportunist is provided, terbinafine being the drug with the most potent activity.


[Nutritional evaluation, micronutrient deficiencies and anemia among female adolescents in an urban and a rural zone from Zulia state, Venezuela].
Female adolescents in reproductive age are a susceptible group to anemia and micronutrient deficiencies. The objective of this study was to know the nutritional, anthropometric and dietetic status, the prevalence of anemia, depletion of iron deposits (FeD) and Vitamin A deficiency (VAD) in female adolescents. Seventy-eight not pregnant female adolescents (15.9 +/- 1.1 years old), from an urban and a periurban zone of Maracaibo, and a rural zone near this city, without infectious and inflammatory processes, were analyzed. Anemia in adolescents was considered when Hb < 120 g/L; FeD: ferritin < 12 microg/L; VAD serum retinol <20 microg/dL; risk of VAD (RVAD) 20-30 microg/dL. The data were analyzed with the SAS program and expressed as Means +/- Standard Deviations, statistical significance was considered when p < 0.05. The percentage of caloric and protean adjustment in all groups was below the daily requirements. Adolescents from the rural zone showed significant lower values of weight (p = 0.0024), height (p = 0.0027), body mass index BMI (p = 0.0487), fatty area (p = 0.0183), MCV (p = 0.0241), MCH (p = 0.0488), MHCC (p = 0.0228), and the highest prevalence of anemia (66.67%), anemia+FeD (33.33%), and anemia+FeD+RVAD (5.56%), with respect to adolescents from the urban zone. Although, anemic adolescents from the rural zone showed a non significant decrease of the iron percentage adjustment. Iron requirements are increased during adolescence, reaching a maximum at the peak of growth and remaining almost as high in girls after menarche, to replace menstrual losses. The low iron status among adolescents from the rural zone determine that this is a high risk group to anemia and FeD and they require prevention, control and suplementation strategies.


High tolerance for oral galactose in classical galactosaemia: dietary implications.
To study the relevance of restricting the exogenous intake of small amounts of galactose, such as from fruit and vegetables, in patients with classical galactosaemia. For a period of six weeks, increasing doses of oral galactose to a maximum of 600 mg per day, were added to a very strict galactose restricted diet in three adolescent patients homozygous for the Q188R mutation. During the study, physical examination, including an extended ophthalmic examination, and laboratory studies were performed on a weekly basis. No significant change in any of the studied clinical or biochemical parameters was observed. These findings provide further evidence that attempts to exclude trace amounts of galactose from the diet are not justified. Once the diet is made more liberal, a long term follow up study will be necessary.


Epithelioid glioblastomas stratify into established diagnostic subsets upon integrated molecular analysis.
Epithelioid glioblastoma (eGBM) is a newly defined and rare GBM variant in the current WHO 2016 classification. BRAF V600E mutation is overrepresented in these tumors and there is known some morphological overlap with anaplastic epithelioid PXA (ePXA). In order to further elucidate this diagnostic category, we molecularly characterized 64 pediatric and adult examples initially diagnosed as "eGBM." Tumors were analyzed using array based methylation and direct sequencing of the BRAF and TERT genes. Our results demonstrated considerable molecular and clinical heterogeneity among eGBM cohort. Methylation patterns, copy number alterations, and mutational analysis data, in combination with clinical findings disclosed three different, well established tumor subtypes: (i) PXA-like tumors with favorable prognosis, predominantly in children and young adults (38), (ii) IDHwt GBM-like tumors with poor prognosis, mainly occurring in older adults, albeit with more frequent BRAF mutations (17), and (iii) RTK1 pediatric GBM-like neoplasms of intermediate prognosis in children and young adults, associated with chromothripsis and frequent PDGFRA amplifications (9). We conclude that the histopathologically defined eGBM do not represent a single diagnostic entity, but rather at least three molecularly and biologically distinct categories. Therefore, additional molecular testing through genome-wide molecular profiling is recommended to further stratify these rare cases.


Turgor regulation of sucrose transport in sugar beet taproot tissue.
Sink tissues that store osmotically active compounds must osmoregulate to prevent excessively high turgor. The ability to regulate turgor may be related to membrane transport of solutes and thus sink strength. To study this possibility, the kinetics of sugar uptake were determined in sugar beet (Beta vulgaris L.) taproot tissue discs over a range of cell turgors. Sucrose uptake followed biphasic kinetics with a high affinity saturating component below 20 millimolar and a low affinity linear component at higher concentrations. Glucose uptake exhibited only simple saturation type kinetics. The high affinity saturating component of sucrose and glucose uptake was inhibited by increasing cell turgor (decreasing external mannitol concentrations). The inhibition was evident as a decrease in V(max) but no effect on K(m). Sucrose uptake by tissue equilibrated in dilute buffer exhibited no saturating component. Ethylene glycol, a permeant osmoticum, had no effect on uptake kinetics, suggesting that the effect was due to changes in cell turgor and not due to decreased water potential per se. p-(Chloromercuri)benzene sulfonic acid (PCMBS) inhibited sucrose uptake at low but not high cell turgor. High cell turgor caused the tissue to become generally leaky to potassium, sucrose, amino acids, and reducing sugars. PCMBS had no effect on sucrose leakage, an indication that the turgor-induced leakage of sucrose was not via back flow through the carrier. The ability of the tissue to acidify the external media was turgor dependent with an optimum at 300 kilopascals. Acidification was sharply reduced at cell turgors above or below the optimum. The results suggest that the secondary transport of sucrose is reduced at high turgor as a result of inhibition of the plasma membrane ATPase. This inhibition of ATPase activity would explain the reduced V(max) and leakiness to low molecular weight solutes. Cell turgor is an important regulator of sucrose uptake in this tissue and thus may be an important determinant of sink strength in tissues that store sucrose.


Alcohol and retinoids.
This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Hirokazu Yokoyama and David Crabb. The presentations were (1) Roles of vitamin A, retinoic acid, and retinoid receptors in the expression of liver ALDH2, by J. Pinaire, R. Hasanadka, M. Fang, and David W. Crabb; (2) Alcohol, vitamin A, and beta-carotene: Adverse interactions, by M. A. Leo and Charles S. Lieber; (3) Retinoic acid, hepatic stellate cells, and Kupffer cells, by Hidekazu Tsukamoto, K. Motomura, T. Miyahara, and M. Ohata; (4) Retinoid storage and metabolism in liver, by William Bosron, S. Sanghani, and N. Kedishvili; (5) Characterization of oxidation pathway from retinol to retinoic acid in esophageal mucosa, by Haruko Shiraishi, Hirokazu Yokoyama, Michiko Miyagi, and Hiromasa Ishii; and (6) Ethanol in an inhibitor of the cytosolic oxidation of retinol in the liver and the large intestine of rats as well as in the human colon mucosa, by Ina Bergheim, Ina Menzl, Alexandr Parlesak, and Christiane Bode.


Peer relationships and adjustment in children with cancer.
Evaluated the psychosocial adaptations of children with cancer (n = 24, ages 8-18) as compared with same classroom controls on indices of (a) peer- and self-perceptions of sociability, aggression, and social isolation; (b) overall popularity; (c) mutual friendships; (d) feelings of loneliness; and (e) self-concept in multiple domains. Although the peer report data showed that children with cancer had a social reputation as significantly more socially isolated, no significant differences were found for their popularity, number of mutual friends, loneliness, or self-worth. Findings suggest that children with cancer have a reputation as more socially isolated, but differences were not found on measures of acceptance by peers, self-concept, or loneliness.


Application of the Network Model to Gas Diffusion in Moist Porous Media.
Millington's description of pore structure in porous media is compared with conclusions based on the network theory. Experimental gas-diffusion data for moist sand indicate that this porous material has a network structure in which each pore is connected to about 15 other pores.


Antioxidant and mercury chelating activity of Psidium guajava var. pomifera L. leaves hydroalcoholic extract.
Mercury (Hg) is widely distributed in the environment and is known to produce several adverse effects in organisms. The aim of the present study was to examine the in vitro antioxidant activity and Hg chelating ability of the hydroalcoholic extract of Psidium guajava leaves (HEPG). In addition, the potential protective effects of HEPG against Hg(II) were evaluated using a yeast model (Saccharomyces cerevisiae). HEPG was found to exert significant antioxidant activity in 2,2-diphenyl-1-picrylhydrazyl scavenger and inhibition of lipid peroxidation induced by Fe(II) assays in a concentration-dependent manner. The extract also exhibited significant Hg(II) chelating activity. In yeast, Hg(II) induced a significant decrease in cell viability. In contrast, HEPG partially prevented the fall in cell viability induced by Hg(II). In conclusion, HEPG exhibited protective effects against Hg(II)-mediated toxicity, which may be related to both antioxidant and Hg(II)-chelating activities.


Metabolic adaptations in goat mammary tissue during pregnancy and lactation.
Metabolic adaptations of goat mammary tissue during pregnancy and lactation were monitored in serial biopsies of the tissue. Changes in the synthetic capacity of secretory cells were studied by combining measurements of enzyme activities with short-term culture of mammary explants to measure lactose, casein and total protein synthesis. By these criteria, the main phase of mammary differentiation began in late pregnancy and was essentially complete by Week 5 of lactation, coinciding with the achievement of peak milk yield. While milk yield declined after Week 5, the activities of key enzymes expressed per mg DNA and the rates of lactose and casein synthesis in mammary explants were maintained over a considerable period. The results suggest that changes in the synthetic capacity of epithelial cells may account for much of the rise in milk yield in early lactation, but are not responsible for the declining phase of milk production characteristic of lactation in ruminants.


Cystic hygroma: A difficult airway and its anaesthetic implications.
A 2-month-old child presented with gross and huge swelling on the left side of the neck with difficulty in feeding. It was diagnosed to be cystic hygroma and a decision was made to excise the swelling to enable the child thrive better. Difficult intubation was anticipated and the child was intubated with inhalation induction. The intra-operative period was smooth and the tumour was excised completely. Post-operatively, it was decided to ventilate the child because of airway difficulties.


Mureidomycin A, a new inhibitor of bacterial peptidoglycan synthesis.
Mureidomycin A (MRD), a novel peptidylnucleoside antibiotic with antipseudomonal activity, inhibited not only peptidoglycan synthesis but also lipid-intermediate formation from UDP-N-acetylmuramyl (MurNAc)-pentapeptide and UDP-N-acetylglucosamine in an in vitro peptidoglycan-synthesizing system, using ether-treated cells of Pseudomonas aeruginosa. Both types of inhibition by MRD disappeared when UDP-MurNAc-pentapeptide was preincubated with ether-treated cells. Moreover, MRD completely inhibited lipid-intermediate I (undecaprenyl-p-p-MurNAc-pentapeptide) formation at a concentration below the MIC. From these results, it was concluded that the real target of MRD's action was translocase, which catalyzes lipid-intermediate I formation from UDP-MurNAc-pentapeptide and a lipid carrier.


Ecoimmunology: is there any room for the neuroendocrine system?
Ecological Immunology assumes that immunological defenses must be minimized in terms of cost (energy expenditure). To reach this goal, a complex and still largely unexplored strategy has evolved to assure survival. From invertebrates to vertebrates, an integrated immune-neuroendocrine response appears to be crucial for the hierarchical redistribution of resources within the body according to the specific ecological demands. Thus, on the basis of experimental data on the intimate relationship between stress and immune responses that has been maintained during evolution, we argue that a broader perspective based on the integration of immune and neuroendocrine responses should be adopted to describe the comprehensive strategy that the body utilizes to adapt to dynamic environmental conditions. We discuss the hypothesis that a bow-tie architecture might be suitable to describe the variety of immune-neuroendocrine inputs that continuously target cells and organs while, at the same time, fulfilling the basic requirement of minimizing the cost of immune-neuroendocrine responses. Bow-tie architectures are able to convert a variety of stimuli (fan in) into a wide range of fine-tuned responses (fan out) by passing through the integrating activity of a core (knot) constituted by a limited number of elements. Finally, we argue that the ecologically negotiated immune-neuroendocrine strategies may have deleterious effects in the post-reproductive period of life when, at least in humans, chronic, low-grade, systemic inflammation develops, in accordance with the antagonistic pleiotropy theory of aging.


Discovery platform for inhibitors of IgH gene enhancer activity.
Immunoglobulin heavy chain (IgH) translocations are common and early oncogenic events in B cell and plasma cell malignancies including B cell non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM). IgH translocations bring oncogenes into close proximity with potent enhancer elements within the IgH locus, leading to oncogene up-regulation. As IgH enhancer activity is tightly controlled by B cell lineage-specific signaling and transcriptional networks, we hypothesized that IgH enhancers are potentially druggable targets/elements. To test this, we developed a molecular imaging-based high-throughput screening platform for discovering inhibitors of IgH enhancer-driven transcriptional activity. As proof of concept, we identified a low micromolar potency molecule (compound 30666) that inhibited immunoglobulin production by MM cells and blocked expression of an array of IgH translocation-induced oncogenes (CCND1, FGFR3/MMSET, and MYC) in MM and NHL cell lines. Prolonged exposure to 30666 significantly reduced the viability of IgH translocation-positive NHL and MM cells, but was less effective against cells lacking IgH translocations. Compound 30666 exhibited suitable pharmacological properties, including metabolic stability in liver microsomes and oral bioavailability in mice, and demonstrated preclinical anti-MM activity in a plasmacytoma mouse model. Our work suggests that IgH enhancers are attractive and potentially druggable targets for IgH translocation driven malignancies.


Polysaccharide-inducible endoglucanases from Lentinula edodes exhibit a preferential hydrolysis of 1,3-1,4-β-glucan and xyloglucan.
Three genes encoding glycoside hydrolase family 12 (GH12) enzymes from Lentinula edodes, namely Lecel12A, Lecel12B, and Lecel12C, were newly cloned by PCR using highly conserved sequence primers. To investigate enzymatic properties, recombinant enzymes encoded by L. edodes DNAs and GH12 genes from Postia placenta (PpCel12A and PpCel12B) and Schizophyllum commune (ScCel12A) were prepared in Brevibacillus choshinensis. Recombinant LeCel12A, PpCel12A, and PpCel12B, which were grouped in GH12 subfamily 1, preferentially hydrolyzed 1,3-1,4-β-glucan. By contrast, LeCel12B, LeCel12C, and ScCel12A, members of the subfamily 2, exhibited specific hydrolysis of xyloglucan. These results suggest that two subfamilies of GH12 are separated based on the substrate specificity. Transcript levels of L. edodes genes increased 72 h after growth of L. edodes mycelia cells in the presence of plant cell wall polymers such as xyloglucan, 1,3-1,4-β-glucan, and cellulose. These results suggest that L. edodes GH12 enzymes have evolved to hydrolyze 1,3-1,4-β-glucan and xyloglucan, which might enhance hyphal extension and nutrient acquisition.


A Framework for Stochastic Optimization of Parameters for Integrative Modeling of Macromolecular Assemblies.
Integrative modeling of macromolecular assemblies requires stochastic sampling, for example, via MCMC (Markov Chain Monte Carlo), since exhaustively enumerating all structural degrees of freedom is infeasible. MCMC-based methods usually require tuning several parameters, such as the move sizes for coarse-grained beads and rigid bodies, for sampling to be efficient and accurate. Currently, these parameters are tuned manually. To automate this process, we developed a general heuristic for derivative-free, global, stochastic, parallel, multiobjective optimization, termed StOP (Stochastic Optimization of Parameters) and applied it to optimize sampling-related parameters for the Integrative Modeling Platform (IMP). Given an integrative modeling setup, list of parameters to optimize, their domains, metrics that they influence, and the target ranges of these metrics, StOP produces the optimal values of these parameters. StOP is adaptable to the available computing capacity and converges quickly, allowing for the simultaneous optimization of a large number of parameters. However, it is not efficient at high dimensions and not guaranteed to find optima in complex landscapes. We demonstrate its performance on several examples of random functions, as well as on two integrative modeling examples, showing that StOP enhances the efficiency of sampling the posterior distribution, resulting in more good-scoring models and better sampling precision.


Controllable Environment Protein Corona-Disguised Immunomagnetic Beads for High-Performance Circulating Tumor Cell Enrichment.
The enrichment performance of immunomagnetic beads (IMBs) in blood samples is usually challenging due to the ungoverned, in situ-formed protein corona, as it generally leads to negative effects, such as impeded targeting capacity and unwanted nonspecific absorption. On the contrary, a controlled protein premodification of IMBs with diverse functional environment (blood) proteins endows the composites with a new biological identity and may improve the anti-nonspecific ability, resulting in promising isolation benefits for circulating tumor cell (CTC) enrichment and downstream analyses. Specifically, fetal bovine serum and the four most abundant blood proteins, including human serum albumin, fibrinogen, immunoglobulin, and transferrin, were separately applied in this work. Conclusively, the biological properties of the applied protein corona camouflage have a great influence on the capture performance of IMBs, and certain proteins can enhance the enrichment performance to a large extent. Promisingly, human serum albumin-camouflaged IMBs (HSA-PIMBs) achieved a capture efficiency of 84.0-90.0% and significantly minimized nonspecific absorbed leukocytes to 164-264 in blood samples (0.5 mL, 25-55 model CTCs). Furthermore, HSA-PIMBs isolated 62-505 CTCs and 13-31 leukocytes from the blood samples of five cancer patients. The novel environment camouflage strategy provides a new insight into protein corona utilization and may improve the performance of targeted nanomaterials in a complex biological environment.


How self psychology found me.
The author describes the evolution of self psychology from Kohut's early work to the present through the lens of her own life and work.


Virus-Mediated Genome Editing via Homology-Directed Repair in Mitotic and Postmitotic Cells in Mammalian Brain.
Precise genome editing via homology-directed repair (HDR) in targeted cells, particularly in vivo, provides an invaluable tool for biomedical research. However, HDR has been considered to be largely restricted to dividing cells, making it challenging to apply the technique in postmitotic neurons. Here we show that precise genome editing via HDR is possible in mature postmitotic neurons as well as mitotic cells in mice brain by combining CRISPR-Cas9-mediated DNA cleavage and the efficient delivery of donor template with adeno-associated virus (AAV). Using this strategy, we achieved efficient tagging of endogenous proteins in primary and organotypic cultures in vitro and developing, adult, aged, and pathological brains in vivo. Thus, AAV- and CRISPR-Cas9-mediated HDR will be broadly useful for precise genome editing in basic and translational neuroscience.


Metoprolol in dilated cardiomyopathy: is it possible to identify factors predictive of improvement? The Heart Muscle Disease Study Group.
Some controlled clinical trials showed a beneficial effect of beta-blockers on symptoms, exercise tolerance, and left ventricular function in dilated cardiomyopathy. The purpose of this study was to investigate if there are clinical variables at baseline that could predict a favorable response to long-term metoprolol therapy. Since November 1987, 94 consecutive patients with dilated cardiomyopathy and left ventricular ejection fraction less than 0.40 were treated with metoprolol (mean final dosage, 136 +/- 32 mg) associated with tailored medical therapy with digitalis, diuretics, and angiotensin-converting enzyme inhibitors. Eighty-four surviving patients had a complete 2-year noninvasive follow-up period. Ten patients died or were transplanted before the final assessment. Improvement was defined according to a clinical score based on left ventricular ejection fraction (increase > or = 10 U), left ventricular end-diastolic diameter (decrease > or = 10%), regression of restrictive filling pattern, New York Heart Association functional class, exercise tolerance (increase > or = 2 minutes), and cardiothoracic ratio (decrease > or = 10%). According to these criteria, 48 patients (51.1%) were classified as improved. Multivariate analysis identified a group of patients with a history of mild hypertension (blood pressure between 140/90 and 170/100 mmHg) and significantly higher probability of improvement with longterm metoprolol (odds ratio [OR], 2.22; 95% confidence interval, 1.25-3.94; P = .007). Among the 71 patients with normal blood pressure (< 140/90 mmHg), heart rate in upright position (100 vs 75 beats/min: OR, 2; 95% confidence interval, 1.38-4.94; P = .003), left ventricular ejection fraction 0.20-0.33 versus less than 0.20 (OR, 4.72; 95% confidence interval, 1.06-21.04; P = .042), and New York Heart Association class I-II versus III-IV (OR, 2.74; 95% confidence interval, 0.97-7.75; P = .05) were significantly associated with a positive response to metoprolol. At baseline, both supine and upright heart rate were significantly higher in patients who improved, but heart rate in the upright position was the most significant predictor of improvement in patients with normal blood pressure at multivariate analysis. According to the authors' logit model, patients with a history of mild hypertension or with a higher resting heart rate, associated with controlled symptoms of heart failure (New York Heart Association class I-II) or moderate to severe left ventricular ejection fraction (range, 0.20-0.33) showed a remarkable probability of long-term (2-year) improvement on metoprolol.


Multiscale Characterization of Engineered Cardiac Tissue Architecture.
In a properly contracting cardiac muscle, many different subcellular structures are organized into an intricate architecture. While it has been observed that this organization is altered in pathological conditions, the relationship between length-scales and architecture has not been properly explored. In this work, we utilize a variety of architecture metrics to quantify organization and consistency of single structures over multiple scales, from subcellular to tissue scale as well as correlation of organization of multiple structures. Specifically, as the best way to characterize cardiac tissues, we chose the orientational and co-orientational order parameters (COOPs). Similarly, neonatal rat ventricular myocytes were selected for their consistent architectural behavior. The engineered cells and tissues were stained for four architectural structures: actin, tubulin, sarcomeric z-lines, and nuclei. We applied the orientational metrics to cardiac cells of various shapes, isotropic cardiac tissues, and anisotropic globally aligned tissues. With these novel tools, we discovered: (1) the relationship between cellular shape and consistency of self-assembly; (2) the length-scales at which unguided tissues self-organize; and (3) the correlation or lack thereof between organization of actin fibrils, sarcomeric z-lines, tubulin fibrils, and nuclei. All of these together elucidate some of the current mysteries in the relationship between force production and architecture, while raising more questions about the effect of guidance cues on self-assembly function. These types of metrics are the future of quantitative tissue engineering in cardiovascular biomechanics.


Functional and taxonomic dynamics of an electricity-consuming methane-producing microbial community.
The functional and taxonomic microbial dynamics of duplicate electricity-consuming methanogenic communities were observed over a 6 months period to characterize the reproducibility, stability and recovery of electromethanogenic consortia. The highest rate of methanogenesis was 0.72 mg-CH4/L/day, which occurred during the third month of enrichment when multiple methanogenic phylotypes and associated Desulfovibrionaceae phylotypes were present in the electrode-associated microbial community. Results also suggest that electromethanogenic microbial communities are very sensitive to electron donor-limiting open-circuit conditions. A 45 min exposure to open-circuit conditions induced an 87% drop in volumetric methane production rates. Methanogenic performance recovered after 4 months to a maximum value of 0.30 mg-CH4/L/day under set potential operation (-700 mV vs Ag/AgCl); however, current consumption and biomass production was variable over time. Long-term functional and taxonomic analyses from experimental replicates provide new knowledge toward understanding how to enrich electromethanogenic communities and operate bioelectrochemical systems for stable and reproducible performance.


Chickenpox, chickenpox vaccination, and shingles.
Chickenpox in the United Kingdom, where vaccination is not undertaken, has had a stable epidemiology for decades and is a routine childhood illness. Because of vaccination, chickenpox is now a rarity in the USA. In the UK vaccination is not done because introduction of a routine childhood vaccination might drive up the age at which those who are non-immune get the illness (chickenpox tends to be more severe the older you are), and the incidence of shingles may increase. The United Kingdom is waiting to see what happens in countries where vaccination is routine.


KATP channels contribute to beta- and adenosine receptor-mediated pulmonary vasorelaxation.
ATP-sensitive K+ (KATP) channels have been implicated in the regulation of vasomotor tone in aortic, mesenteric, and pulmonary vascular smooth muscle. Several investigators have described an association between KATP channels and isoproterenol (Iso)-stimulated relaxation responses. To study the relationship between receptor-dependent pulmonary vasorelaxation and KATP channels, we examined the response to agonists that generate adenosine 3',5'-cyclic monophosphate at two distinct levels of the signal transduction pathway after inhibition or activation of KATP channels in isolated rat pulmonary artery rings. Cumulative concentration responses to beta-adrenergic receptor stimulation (Iso), purinergic receptor stimulation [adenosine (Ado)], and direct stimulation of adenylate cyclase [forskolin (FSK)] were studied with and without concurrent inhibition of KATP channels (glibenclamide or tolbutamide). In addition, the effect of direct KATP channel activation (cromakalim) on the response to beta-adrenergic and purinergic receptor stimulation was determined. Last, we investigated the influence of KATP channel inhibition on endothelium-dependent and -independent mechanisms of pulmonary vasorelaxation linked to guanosine 3',5'-cyclic monophosphate production. KATP channel inhibition impaired the response to Iso and Ado. Activation of KATP channels caused a leftward shift in the dose responses of Iso and Ado, with a significant decrease in the 50% effective concentration for each agent. KATP channel inhibition did not impair the pulmonary arterial vasorelaxation response to FSK, acetylcholine, or sodium nitroprusside. KATP channels appear to contribute to beta-adrenergic and purinergic receptor-stimulated vasorelaxation in rat pulmonary arteries.


Validation of performance of certified medical assistants in preschool vision screening examination.
Preschool vision screening examination is still a new concept in Nepal. There is a need for developing cost-effective tools for detecting amblyogenic factors in Nepalese children. Certified medical assistants (CMA) are health personnel who work in village health posts. To find out the effectiveness of vision screening by certified medical assistants using simple tools like an HOTV chart and the Red Reflex test. A cross sectional and validation study was carried out in two phases. In the first phase, 20 CMAs from each Village Development Centre (VDC) of the Bhaktapur District were given training on visual acuity test by using an HOTV chart, Bruckner test by using a retinoscope and the test for ocular alignment by a torch light. In the second phase, children aged 3 - 7 years were examined by trained certified medical assistants in five remote VDCs of Bhaktapur District. These children underwent the gold standard examination by two pediatric ophthalmologists blind to the CMAs± findings. The mean age of children was 5.26 ± 376 years. The overall sensitivity of certified medical assistants examination was 58 % and the specificity was 98 %. While comparing the test characteristics of different examination tools, the HOTV test was found to be the most effective one with the sensitivity of 80 % and the specificity of 98 %. Vision screening by certified medical assistants can help in detection and early referral of children having amblyogenic risk factors with high sensitivity. The HOTV test is the most effective one with high sensitivity and specificity. In developing countries like Nepal,where access to regular eye examination is a rare possibility, preschool vision screening using the HOTV test can be effective.


Wilson's disease--a rare psychiatric presentation.
The development of extrapyramidal syndrome characterised by rigidity, bradykinesia, dysphagia and dysarthria in a male individual with four distinct episodes of (mania like) behavioural disturbances with fairly good remission in a time frame of five years, in a male individual, was suspected to develop the neurological manifestations of Wilson's disease and was investigated. In the absence of Kayser-Fleischer ring by slit-lamp examination and with normal copper and ceruloplasmin serum levels, the diagnosis was possible because of the positive findings of the magnetic resonance imaging (MRI) studies and increased 24 hours urinary copper levels with the penicillamine challenge test. The findings and its implications are highlighted and discussed.


The Double-Edged Sword of Military Response to Societal Disruptions: A Systematic Review of the Evidence for Military Personnel as Pathogen Transmitters.
Given their lack of immunity and increased exposure, military personnel have the potential to serve as carriers or reservoirs for infectious diseases into or out of the deployment areas, but, to our knowledge, the historical evidence for such transmission events has not previously been reviewed. Using PubMed, we performed a systematic review of published literature between 1955 and 2018, which documented evidence for military personnel transporting infectious pathogens into or out of deployment areas. Of the 439 articles screened, 67 were included for final qualitative and quantitative review. The data extracted from these articles described numerous instances in which thousands of military service members demonstrated potential or actual transmission and transportation of multiple diverse pathogens. These data underscore the immense importance preventive medical professionals play in mitigating such risk, how their public health efforts must be supported, and the importance of surveillance in protecting both military and civilian populations.


Second polar body incorporation into a blastomere results in 46,XX/69,XXX mixoploidy.
A case of 46,XX/69,XXX mixoploidy is described. The patient had a normal 46,XX diploid karyotype in lymphocytes but a triploid 69,XXX cell line in most of her fibroblasts. In order to learn more about the underlying mechanism resulting in mixoploidy, we studied short tandem repeat polymorphisms (STRPs) in lymphocyte DNA of the patient's parents and in both lymphocyte and fibroblast DNA of the proband. The findings showed maternal origin of the supernumerary chromosome complement and are best explained by second polar body incorporation into a blastomere.


Acute pulmonary edema associated with obstruction of the airways. Case report.
Negative pressure pulmonary edema has been defined as non-cardiogenic edema, with transudation of fluid to the interstitial space of the lungs due to an increase in negative intrathoracic pressure secondary to obstruction of the upper airways. This is the case of a healthy patient who underwent general anesthesia and developed acute pulmonary edema after extubation. A 23-year old female patient, physical status ASA II, underwent gynecologic videolaparoscopy under general anesthesia. The procedure lasted 3 hours without intercurrence. After extubation the patient developed laryngeal spasm and reduction in oxygen saturation. The patient improved after placement of an oral cannula and administration of oxygen under positive pressure with a face mask. Once the patient was stable she was transferred to the recovery room where, shortly after her arrival, she developed acute pulmonary edema with elimination of bloody serous secretion. Treatment consisted of elevation of the head, administration of oxygen via a face mask, furosemide and fluid restriction. Chest X-ray was compatible with acute pulmonary edema and normal cardiac area. Electrocardiogram (ECG), echocardiogram and cardiac enzymes were normal. The condition of the patient improved and she was discharged from the hospital the following day, asymptomatic. Acute pulmonary edema associated with obstruction of the upper airways can aggravate surgical procedures with low morbidity, affecting mainly young patients. Early treatment should be instituted because it has a fast evolution and, in most cases, resolves without lasting damages.


Normal hip in children: correlation of US with anatomic and cryomicrotome sections.
Full and simultaneous exploitation of features designed to maximize signal-to-noise ratio with the new generation of ultrasound equipment enabled detailed sonographic depiction of the anatomy of the hip and its surroundings. Scanning in familiar planes provided images that are easier to interpret. In addition, correlation of these images with cryomicrotome sections and histochemical studies disclosed several new findings. The articular cartilage of infant hips-composed mostly of water-is anechoic. However, the hyaline cartilage-which contains many vascular channels, columns of cartilage cells, and mesenchymal stroma-appears as alternating hypoechoic or anechoic columns and echogenic columns. The fibrocartilage of the limbus, on the other hand, is echogenic, as are other fibrous tissues. As expected, the points of attachment of the distal aspect of the synovial membrane, the fibrous capsule, and the ligaments in relation to the epiphyseal growth plate, varied with age, as did the characteristics of the cartilaginous structures. Familiarization with the sonographic appearance of normal hip anatomy in subjects of all ages is a first step toward recognition of various pathologic entities of the hip.


Peripherally applied candesartan inhibits central responses to angiotensin II in conscious rats.
In the brain, angiotensin II (Ang II) induces various effects such as blood pressure increase, the release of arginine vasopressin (AVP) and drinking behaviour. In the present study, we investigated the ability of the angiotensin II type-I (AT(1)) receptor antagonist, candesartan, administered peripherally, to block the central effects of Ang II. Experiments were performed in conscious rats instrumented with an intracerebroventricular (i.c.v.) cannula or a guide cannula into the paraventricular nucleus (PVN) and arterial and femoral catheters. Candesartan was administered intravenously (i.v.) at doses of 0.01, 0.1, 1 or 10 mg/kg. Controls received vehicle (0.05 N Na(2)CO(3)). The drinking response ( n=10-11 per group), the pressor response ( n=7-8) and the release of AVP into the circulation ( n=10-11) following i.c.v. Ang II (100 ng) were measured 0.5, 2, 4 and 24 h following i.v. drug application. Candesartan inhibited the central responses to i.c.v. injected Ang II dose- and time-dependently. At the highest dose (10 mg/kg), the drinking and pressor responses and the release of AVP in response to i.c.v. Ang II were completely blocked at 4 h and still markedly inhibited 24 h after the antagonist application (by 85%, 48% and 86%, respectively). The lowest dose of the antagonist was without effect. In a further experiment, the release of AVP induced by microinjection of Ang II (100 ng) into the PVN was determined before and 4 h after administration of vehicle or candesartan (1 mg/kg, i.v.). Candesartan completely blocked the AVP release into the circulation induced by Ang II microinjection into the PVN. Our results demonstrate that candesartan administered peripherally effectively inhibits responses mediated by AT(1) receptors localised in periventricular brain regions as well as inside the blood-brain-barrier.


Ecophysiological traits in C3 and C4 grasses: a phylogenetically controlled screening experiment.
Experimental evidence demonstrates a higher efficiency of water and nitrogen use in C(4) compared with C(3) plants, which is hypothesized to drive differences in biomass allocation between C(3) and C(4) species. However, recent work shows that contrasts between C(3) and C(4) grasses may be misinterpreted without phylogenetic control. Here, we compared leaf physiology and growth in multiple lineages of C(3) and C(4) grasses sampled from a monophyletic clade, and asked the following question: which ecophysiological traits differ consistently between photosynthetic types, and which vary among lineages? C(4) species had lower stomatal conductance and water potential deficits, and higher water-use efficiency than C(3) species. Photosynthesis and nitrogen-use efficiency were also greater in C(4) species, varying markedly between clades. Contrary to previous studies, leaf nitrogen concentration was similar in C(4) and C(3) types. Canopy mass and area were greater, and root mass smaller, in the tribe Paniceae than in most other lineages. The size of this phylogenetic effect on biomass partitioning was greater in the C(4) NADP-me species than in species of other types. Our results show that the phylogenetic diversity underlying C(4) photosynthesis is critical to understanding its functional consequences. Phylogenetic bias is therefore a crucial factor to be considered when comparing the ecophysiology of C(3) and C(4) species.


Effects of Amine Oxide Surfactants on Reactions of Bromide and Hydroxide Ions with Methylnaphthalene-2-Sulfonate.
The SN2 reaction of Br- with methylnaphthalene-2-sulfonate (MeONs) in water is accelerated by micelles of tetradecyldialkyl amine oxide (alkyl = methyl, n-propyl) and rates increase sharply in HBr due to increased binding of Br- to the protonated amine oxide. Second-order rate constants at the micellar surface are similar to those at surfaces of trialkylammonium and sulfobetaine micelles. The reaction of OH- with MeONs is weakly inhibited by amine oxide micelles, showing that dispersive, as well as coulombic and charge-dipole, forces play a major role in the association of ions with surfaces of micellar aggregates. Copyright 1999 Academic Press.


Approaches to worker rehabilitation by occupational and physical therapists in the United States: factors impacting practice.
Work-related rehabilitation services have changed in nature and scope since their inception in the late 1970s. A review of the literature reveals a large body of published data concerning the various approaches used by therapists in this practice area, but a limited number of comparison studies documenting the value of one approach over the other. This national survey of physical and occupational therapists in the US was conducted in 2002, and examined the prevailing trends in service provision, and factors that determine the nature of services provided to clients. Results indicate that services continue the move to onsite service provision and an emphasis on prevention, but that select services, such as onsite job analysis and comprehensive, inter-disciplinary programs are being used to a limited degree. Research that examines the relative contributions of selected work-related services to successful and efficient return to work outcomes is necessary to identify best practice approaches. Therapists and insurance providers should work more closely in exchange of data that will ensure optimal program design and funding.


Membrane dopamine beta-hydroxylase: a precursor for the soluble enzyme in the bovine adrenal medulla.
Searching for endogenous proteolytic activities converting the membrane form of dopamine beta-hydroxylase (dopamine beta-monooxygenase, DBH) into the soluble and releasable form, DBH was monitored enzymatically and immunologically in aqueous and detergent-solubilized extracts of the adrenomedullary fractions. Degradation of the soluble DBH and acidic chromogranins by activation of endogenous proteases occurred during lysis in H2O. Shifts in the hydrophobicity of the membrane DBH were also apparent. Loss in enzyme protein or activity was, on the other hand, not observed for buffer-dialysed CG (pH 5-6). Limited proteolysis within the membrane phase was, however, indicated by the shift towards dominance of the intermediate hydrophobic DBH in the buffer-dialysed CG. By two-dimensional, crossed immunoelectrophoresis with cationic detergent the microsomal DBH was immunologically identical to the granule-bound enzyme but differed from the latter in molecular heterogeneity and in susceptibility to proteolytic solubilization by endogenous protease activities. DBH in the membranes of the chromaffin granules was proteolytically solubilized at pH 6-8 and the soluble DBH further degraded at pH 5. The results indicate that a post-translational conversion of the amphiphilic DBH into the soluble form, initiated at the level of the microsomes, may continue within the light and the heavy granule fractions which contain several DBH-converting and degrading proteolytic activities with acid optima.


Copy-up mutants of the plasmid RK2 replication initiation protein are defective in coupling RK2 replication origins.
The broad host range plasmid RK2 replicates and regulates its copy number in a wide range of Gram-negative bacteria. The plasmid-encoded trans-acting replication protein TrfA and the origin of replication oriV are sufficient for controlled replication of the plasmid in all Gram-negative bacteria tested. The TrfA protein binds specifically to direct repeat sequences (iterons) at the origin of replication. A replication control model, designated handcuffing or coupling, has been proposed whereby the formation of coupled TrfA-oriV complexes between plasmid molecules results in hindrance of origin activity and, consequently, a shut-down of plasmid replication under conditions of higher than normal copy number. Therefore, according to this model, the coupling activity of an initiation protein is essential for copy number control and a copy-up initiation protein mutant should have reduced ability to form coupled complexes. To test this model for plasmid RK2, two previously characterized copy-up TrfA mutations, trfA-254D and trfA-267L, were combined and the resulting copy-up double mutant TFrfA protein TrfA-254D/267L was characterized. Despite initiating runaway (uncontrolled) replication in vivo, the copy-up double-mutant TrfA protein exhibited replication kinetics similar to the wild-type protein in vitro. Purified TrfA-254D, TrfA-267L, and TrfA-254D/267L proteins were then examined for binding to the iterons and for coupling activity using an in vitro ligase-catalyzed multimerization assay. It was found that both single and double TrfA mutant proteins exhibited substantially reduced (single mutants) or barely detectable (double mutant) levels of coupling activity while not being diminished in their capacity to bind to the origin of replication. These observations provide direct evidence in support of the coupling model of replication control.


Alterations of sirtuins in mitochondrial cytochrome c-oxidase deficiency.
Sirtuins are NAD+ dependent deacetylases, which regulate mitochondrial energy metabolism as well as cellular response to stress. The NAD/NADH-system plays a crucial role in oxidative phosphorylation linking sirtuins and the mitochondrial respiratory chain. Furthermore, sirtuins are able to directly deacetylate and activate different complexes of the respiratory chain. This prompted us to analyse sirtuin levels in skin fibroblasts from patients with cytochrome c-oxidase (COX) deficiency and to test the impact of different pharmaceutical activators of sirtuins (SRT1720, paeonol) to modulate sirtuins and possibly respiratory chain enzymes in patient cells in vitro. We assayed intracellular levels of sirtuin 1 and the mitochondrial sirtuins SIRT3 and SIRT4 in human fibroblasts from patients with COX- deficiency. Furthermore, sirtuins were measured after inhibiting complex IV in healthy control fibroblasts by cyanide and after incubation with activators SRT1720 and paeonol. To determine the effect of sirtuin inhibition at the cellular level we measured total cellular acetylation (control and patient cells, with and without treatment) by Western blot. We observed a significant decrease in cellular levels of all three sirtuins at the activity, protein and transcriptional level (by 15% to 50%) in COX-deficient cells. Additionally, the intracellular concentration of NAD+ was reduced in patient cells. We mimicked the biochemical phenotype of COX- deficiency by incubating healthy fibroblasts with cyanide and observed reduced sirtuin levels. A pharmacological activation of sirtuins resulted in normalized sirtuin levels in patient cells. Hyper acetylation was also reversible after treatment with sirtuin activators. Pharmacological modulation of sirtuins resulted in altered respiratory chain complex activities. We found inhibition of situins 1, 3 and 4 at activity, protein and transcriptional levels in fibroblasts from patient with COX-deficiency. Pharmacological activators were able to restore reduced sirtuin levels and thereby modulate respiratory chain activities.


Novel alpha-amylase that is highly resistant to chelating reagents and chemical oxidants from the alkaliphilic Bacillus isolate KSM-K38.
A novel alpha-amylase (AmyK38) was found in cultures of an alkaliphilic Bacillus isolate designated KSM-K38. Based on the morphological and physiological characteristics and phylogenetic position as determined by 16S ribosomal DNA gene sequencing and DNA-DNA reassociation analysis, it was suggested that the isolate was a new species of the genus Bacillus. The enzyme had an optimal pH of 8.0 to 9.5 and displayed maximum catalytic activity at 55 to 60 degrees C. The apparent molecular mass was approximately 55 kDa, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and the isoelectric point was around pH 4.2. This enzyme efficiently hydrolyzed various carbohydrates to yield maltotriose, maltohexaose, maltoheptaose, and, in addition, maltose as major end products after completion of the reaction. The activity was not prevented at all by EDTA and EGTA at concentrations as high as 100 mM. Moreover, AmyK38 was highly resistant to chemical oxidation and maintained more than 80% of its original activity even after incubation for 1 h in the presence of excess H2O2 (1.8 M).


Health and spirituality 'walk along' in wellness journey of medical students.
To assess and compare knowledge, attitudes and practices of male and female medical students of Karachi in the context of physical, emotional and spiritual wellness. The cross-sectional questionnaire-based survey was conducted from January to December 2010, comprising randomly selected 800 male/female medical students in eight medical colleges of Karachi. The responses--'never,' 'sometimes,' 'mostly' and 'always' (numbered 0-4 )--were analysed in terms of frequency, proportion and percentages by Predictive Analysis Software (PASW) version 18. Chi-square test was applied for comparison of categorical aspects of wellness, and results were declared significant at p < 0.05. Of the 800 questionnaires, 736 (92%) fully-completed questionnaires comprised the study universe. According to the survey, 503 (68.37%), 504 (68.45%) and 658 (89.35%) medical students were aware of the concept of physical, emotional and spiritual wellness respectively. Males had greater involvement in physical activity (p < 0.001), while females selected healthy diet (p < 0.03). The dimensions of physical and emotional wellness on an aggregate did not differ significantly in both genders, but knowledge and practices of spiritual wellness in females gave them direction to face episodes of anxiety for which males had to take help from mentors and psychologists (p < 0.034, p < 0.0001). Spirituality, the key success factor in better wellness management, was found to be greater among female medical students.


Sufficient and Necessary Open-Loop Stackelberg Strategy for Two-Player Game With Time Delay.
This paper is concerned with both difference and differential leader-follower games with time delay. The problem remains challenging although the leader-follower game for delay-free system has been well studied in the past decades. The main obstacle encountered is the noncausality of strategy design caused by the delay. The key technique developed to overcome the difficulty is the introduction of the new co-states which capture the future information of the control and the new state which contains the past effects. The novel contributions of this paper are as follows. First, the sufficient and necessary solvability condition is given to ensure the existence of a unique open-loop Stackelberg strategy for the difference game. Second, the open-loop strategy is explicitly obtained in terms of decoupled and symmetric Riccati equations. Last but not least, a unique strategy for continuous time systems is also given by applying the techniques developed in this paper.


Human Nop5/Nop58 is a component common to the box C/D small nucleolar ribonucleoproteins.
We have identified an apparent human homolog of the yeast Nop5/Nop58 protein. hNop5/Nop58 codes for a protein of predicted molecular weight 59.6 kDa and is 46.8% identical to Saccharomyces cerevisiae Nop5/Nop58. Immunofluorescent staining with antibodies against hNop5/Nop58 indicate that it is localized primarily to the nucleolus, and coimmunoprecipitation from nuclear extracts demonstrates that hNop5/Nop58 interacts with the box C/D family of snoRNAs. Thus, hNop5/Nop58 is a common component of the box C/D snoRNPs, and joins fibrillarin as the second such component identified and characterized in metazoans.


Health-care reform's great expectations and physician reality.
The Patient Protection and Affordable Care Act will not prove to be the reform for which physicians were long hoping. Private insurance rates will climb sharply, forcing people onto government programs; physician reimbursement will plummet; the physician shortage will worsen; rationing in the form of waiting lists is certain; health care as a whole will worsen; and once fully engaged, nationalization of health care will be irreversible.


Aquaporin expression patterns in the developing mouse salivary gland.
Little is known about the presence of the various membrane-located water channels, aquaporins (AQP), during the prenatal and postnatal development of the mouse submandibular salivary gland (SMG). To learn more about AQPs in the developing aspect of salivary glands, we investigated trends in the expression patterns of several AQPs using the embryonic, early postnatal, and young adult mouse SMGs as models. We have chosen AQPs previously found in salivary glands in other animals. Transcripts of AQPs 1, 3, 4, 5, and 8 were detected by reverse transcription-polymerase chain reaction (RT-PCR) and quantified. Aquaporin proteins 1, 3, 4, and 5, but not AQP protein 8, were detected and quantified using western blotting. The various AQPs showed distinct transcript and protein-expression patterns. The change in trends may indicate that the importance of the various AQPs varies throughout the developmental stages in the mouse SMG. Their presence might be related to cell adhesion, migration, proliferation, apoptosis, transepithelial transport, osmosensing, or cell volume regulation; all roles that in the literature are linked to the various AQPs. Overall, this study demonstrates that AQP presentation varies and has a specific expression pattern during the development of mouse SMG. This feature may be important for glandular anatomical and physiological development.


Robotic-Assisted Neck Dissection: Our Experience.
Introduction Robotic neck dissection surgery allows less invasiveness to significantly improve the aesthetic impact even though it does not compromise the principles of radical cancer procedure. Objective The aim of our work is to describe our personal experience with robotic neck dissection surgery. Methods A retrospective study was conducted by analyzing 10 patients subjected to a robotic neck dissection surgery. In the period from August 2012 to December 2018, these patients have been treated exclusively with robotic lateral-cervical dissection. Five of them were subjected to robotic-assisted transaxillary neck dissection (RATAND) and the other 5 treated with robotic-assisted retroauricular neck dissection (RARAND), then the surgical results have been compared with 5 similar dissections performed by open neck dissection (OND). Results The average surgical time of RATAND was estimated in 166 minutes, the average surgical time of RARAND was estimated in 153 minutes and the average surgical time of OND was estimated in 48 minutes. Both robotic techniques are valid from the oncological and aesthetic point of view, but in terms of surgical time, they are much longer than the open technique. Conclusions In terms of the post-operative decree, in our opinion, the retroauricular technique is more rapid for the purposes of recovery.


[Etiopathogenic factors in colorectal cancer. Genetic and clinical features (first of 2 parts)].
Colorectal Cancer (CRC) is the second cause of death in Spain, reaching the first place in non-smoking population. It is also the tumour with the greatest one-year incidence. The last few years some reduction in its incidence along with a greater 5-year average survival has been observed. Most CRCs develop from benign polyps. Vogelstein's hypothesis suggests an orderly progression from normal mucosa, to a small polyp, to a large polyp and finally to a CRC. In this progression transforming cells will be increasingly charged with molecular alterations. 20% of CRCs have a genetic background although only a fourth of these are genetically based. The APC (or FAP) gene mutation is one of the earlier events that can be seen in tumour progression. When this mutation appears in the germ line it renders Familial Adenomatose Polyposis Syndrome (that evolves to CRC in a 100% of cases) or to the Gardner Syndrome (if it has extracolonic expressions). The p53 mutation is a late event in cellular transformation but it makes a rapid accumulation of mutations an easier process and it confers advantages for survival of the tumour cells. Mutations in the genes implicated in microsatellite instability are related to DNA error repair; their clinical correlates are the Lynch I and II syndromes. Other important genes related to CRC are DCC and ras. CLINICAL FACTORS: Inflammatory Bowel Disease (particularly Crohn's disease) is the most important clinical factor, it may enhance basal risk 30 times. Other risk factors are: previous malignant conditions, pelvic irradiation and previous surgery (cholecystectomy and ureterosigmoidostomy). The endocrinologic factors have a rising importance and so hormonal substitution therapy for menopause and multiparity can provide some protection. The use of NSAIDs can also be protective (specially COX-2 inhibitors). It is important that people who are identified as having a high risk for developing a CRC are subjected to a strict clinical and endoscopic follow-up in order to be able to identify an incipient tumour or to practice prophylactic surgery. The use of hormonal substitution therapy or anti COX-2 NSAIDs can be future useful chemoprophylactic agents.


Walking with Diabetes (WW-DIAB) programme a walking programme for Indonesian type 2 diabetes mellitus patients: A pilot randomised controlled trial.
This pilot study aimed to examine the feasibility and effectiveness of a pedometer-based walking programme in Indonesian type 2 diabetes mellitus patients. Feasibility was assessed by monitoring participant recruitment, retention, and adherence to the step-monitoring and recording instructions. Effectiveness was assessed in a pilot randomised controlled trial. Participants were type 2 diabetes mellitus patients randomly assigned to a pedometer-only (PED-only) group (n = 22) and a pedometer with text message support (PED+) group (n = 21). Outcomes were step counts, self-reported physical activity, social cognitive constructs, glycaemic parameters, and health-related quality of life. These were assessed at baseline, 12-week intervention, and 12 weeks later. Longitudinal analyses using generalised estimating equations were carried out to assess treatment and time effects on study outcomes. All but one participant (98%) attended 12- and 24-week data collection follow-ups. Throughout the study period, 82% of PED+ participants submitted their daily steps log. Daily steps increased in both groups (p < 0.001) but more in the PED+ group (2064 more steps at week 24, 95% confidence interval: 200-3925, p = 0.03). Self-reported physical activity levels and glycaemic parameters increased similarly in the two groups over time (p < 0.05). Improvements in social cognitive processes were seen only in the PED+ group (p < 0.05). There were no significant improvements in health-related quality of life. This study provides preliminary evidence that a pedometer-based walking programme, with or without additional support, is feasible and improves physical activity and glucose levels in Indonesian type 2 diabetes mellitus patients. Greater increases in step counts can result from the provision of text message support and education materials than from the provision of a pedometer only.


Electricity generation from synthesis gas by microbial processes: CO fermentation and microbial fuel cell technology.
A microbiological process was established to harvest electricity from the carbon monoxide (CO). A CO fermenter was enriched with CO as the sole carbon source. The DGGE/DNA sequencing results showed that Acetobacterium spp. were enriched from the anaerobic digester fluid. After the fermenter was operated under continuous mode, the products were then continuously fed to the microbial fuel cell (MFC) to generate electricity. Even though the conversion yield was quite low, this study proved that synthesis gas (syn-gas) can be converted to electricity with the aid of microbes that do not possess the drawbacks of metal catalysts of conventional methods.


The role of fluoroscopy in the removal of tracheobronchial pin aspiration.
In this study, we investigated the role of fluoroscopy in the bronchoscopic removal of aspirated pins. Of 373 patients who underwent bronchoscopy for presumed tracheobronchial foreign body aspiration, 56 pin aspiration cases were selected and divided into two groups according to whether fluoroscopic guidance was required (group I) or not (group II). The localisation of foreign bodies, mortality and morbidity ratios and the duration of the procedures were investigated. Pin aspiration percentage was 15. Pins were mostly located in peripheral airways in group I, and in central airways in group II (p < 0.05). The mean duration of the procedure was 42 +/- 30 min in group I and 17 +/- 13 min in group II (p < 0.01). There was no mortality. Morbidity percentage was 7 in group I and 12 in group II (p > 0.05). No thoracotomy was required in any cases. Fluoroscopic guidance is safe and carries no additional morbidity and mortality and can be used for pins in the tracheobronchial tree.


The Source of Purchased Medications and Its Impact on Medication Mistakes and Hospitalizations.
Older adults self-administer prescribed medication regimens to treat chronic diseases, which can lead to mismanagement, medication-related harm, and hospitalization. Using the National Health and Aging Trends Study (NHATS) dataset, we examined the extent to which the medication source could impact the occurrence of self-reported medication mistakes and hospitalizations in community-dwelling adults aged ≥65 years who managed medications independently (N = 3,899). The majority (65%) picked up medications, 18% had medications delivered, and 17% used both methods. Compared to those picking up their medications, those using delivery only were less likely to have a hospital stay (odds ratio [OR] = 0.61, 95% confidence interval [CI] [0.51, 0.94]) but had no difference in odds of medication mistakes (OR = 1.13, 95% CI [0.57, 2.23]). Those using both methods were more likely to report hospital stays (OR = 1.43, 95% CI [1.11, 1.85]) and medication mistakes (OR = 1.65, 95% CI [1.00, 2.73]). Health care providers should consider medication source when assessing older adults' ability to safely self-manage medications. [Research in Gerontological Nursing, 15(2), 69-75.].


Pigment production in murine melanoma cells is regulated by tyrosinase, tyrosinase-related protein 1 (TRP1), DOPAchrome tautomerase (TRP2), and a melanogenic inhibitor.
Using antibodies that recognize either tyrosinase, tyrosinase-related protein-1 (TRP1), or tyrosinase-related protein-2 (TRP2, DOPAchrome tautomerase), the quantities of those melanogenic enzymes were analyzed in five melanoma cell lines that possess various degrees of melanin production. All cells except JB/MS-W increased melanin production four to 30 times after 4 d of melanocyte-stimulating hormone (MSH) treatment. Melanin production by JB/MS-W cells was always under background, with or without MSH treatment. There was a positive correlation between quantities and synthetic rates of those melanogenic enzymes and their melanin formation or DOPAchrome tautomerase activities. The activity of a heat-resistant melanogenic inhibitory factor was also analyzed. The results showed, surprisingly, that pigmented cells showed higher levels of melanogenic inhibitors activity. Tyrosinase activity was increased dramatically whereas the level of melanogenic inhibitor was remarkably decreased following MSH treatment. Interestingly, melanogenic inhibitor derived from JB/MS-W cells suppressed not only tyrosinase but also DOPAchrome tautomerase, another enzyme functional in melanin production. These results clearly suggest that melanin production is regulated by a subtle balance between the activities of these enzymes and other factors such as the melanogenic inhibitor.


[Change and significance of coagulation function and von Willebrand factor antigen level in HELLP syndrome].
To investigate the changes and clinical significance of blood coagulation function and von Willebrand factor antigen (vWF:Ag) in patients with HELLP syndrome (hemolysis, elevated liver function, low platelet count). The clotting data of patients with severe preeclampsia and HELLP syndrome (observation group) admitted to the department of critical care medicine of the Fifth Center Hospital in Tianjin from May 2015 to December 2019 were retrospectively analyzed, and normal late pregnancy women with the same period were enrolled as the control group. The coagulation indexes such as prothrombin time (PT), activated partial thrombin time (APTT), antithrombin (AT), fibrinogen (Fib), D-dimer and plasma vWF:Ag level were compared between the two groups, and among patients with HELLP syndrome with different disease degree. (1) Sixty-five patients with HELLP syndrome and 65 normal pregnant women with third trimester were included. Both groups were women of childbearing age, and there were no significant difference in the baseline data. (2) The levels of Fib, D-dimer in both groups increased, but they were significantly higher in the observation group than those in the control group [Fib (g/L): 4.94 (4.76, 5.85) vs. 3.58 (2.97, 4.14), D-dimer (mg/L): 3.34 (2.55, 4.32) vs. 1.72 (1.29, 2.08), both P < 0.05], the AT was obviously reduced [62.00 (49.00, 73.00)% vs. 97.50 (90.75, 107.00)%, P < 0.01], and both PT and APTT were in the normal reference range in the two groups. In addition, the plasma vWF:Ag level in the observation group was significantly higher than that in the control group [516.50 (467.20, 563.00)% vs. 246.45 (189.95, 274.10)%, P < 0.01]. (3) According to thrombocytopenia, among the 65 patients with HELLP syndrome, 26 cases were mild [platelet count (PLT) > 100×109/L], 22 cases were moderate [PLT (50-100)×109/L], and 17 cases were severe (PLT < 50×109/L). With the aggravation of the disease, the D-dimer, Fib, vWF:Ag levels in the mild, moderate, severe patients significantly increased, while the AT level significantly decreased, and there was statistically significant difference between the two groups [D-dimer (mg/L): 2.63 (2.60, 2.73), 3.15 (2.55, 3.73), 3.84 (3.52, 4.23); Fib (g/L): 4.23 (4.06, 4.47), 4.72 (4.34, 5.04), 5.43 (5.14, 5.76); vWF:Ag: 465.20 (437.20, 495.40)%, 500.10 (472.40, 534.50)%, 543.50 (521.30, 563.00)%; AT: 67.50 (61.60, 78.00)%, 63.70 (53.30, 70.40)%, 54.40 (44.00, 61.20)%; all P < 0.05]. Patients with HELLP syndrome may show hypercoagulability and excessive expression of peripheral blood vWF:Ag level, which can induce platelet aggregation, leading to thrombocytopenia and thrombotic microangiopathy, and the clinicians should pay attention to that.


Obesity in Nursery School Children in Corum, Turkey.
Regular body mass index (BMI) screenings in schools is important to ensure that 3- to 6-year-old children are not negatively affected by obesity in terms of their current and future health. The aim of this study was to determine the overweight and obesity results of 3- to 6-year-old children and to guide children and their family in making healthier dietary choices by informing them. This analytical-descriptive study was conducted in Corum, Turkey, in the year 2011. The study's sample consisted of all available 3- to 6-year-old children entering nursery school (specifically, the Buharaevler, Karsıyaka, Nasrettin Hoca, Ulukavak, Mimar Sinan, and Sevgi nursery schools). Findings from the study were statistically analyzed using the SPSS 15.0 program. The Chi-square test and analysis of variance (ANOVA) program were used in the comparison of study data. A p-value of less than 0.05 was considered significant. It was determined that 9.5% of the participating female children and 5.2% of the male children were underweight and that the boys were more obese than the girls in general. The correlation between the child's gender and their BMI was not found to be statistically significant (P-value > 0.05). The overweight frequency of the children was 12.1%, and the obesity frequency was 14.3%. Furthermore, it was determined that the obesity rates of the children increased with their age. Accordingly, the correlation between the child's age and BMI was found to be statistically significant (P-value < 0.05). An approach to preventing obesity must not be enacted only in health centers. Schools should also offer information and resources for families in order to prevent obesity in children.


How psychological safety and feeling heard relate to burnout and adaptation amid uncertainty.
Psychological safety-the belief that it is safe to speak up-is vital amid uncertainty, but its relationship to feeling heard is not well understood. The aims of this study were (a) to measure feeling heard and (b) to assess how psychological safety and feeling heard relate to one another as well as to burnout, worsening burnout, and adaptation during uncertainty. We conducted a cross-sectional survey of emergency department staff and clinicians (response rate = 52%; analytic N = 241) in July 2020. The survey measured psychological safety, feeling heard, overall burnout, worsening burnout, and perceived process adaptation during the COVID-19 crisis. We assessed descriptive statistics and construct measurement properties, and we assessed relationships among the variables using generalized structural equation modeling. Psychological safety and feeling heard demonstrated acceptable measurement properties and were correlated at r = .54. Levels of feeling heard were lower on average than psychological safety. Psychological safety and feeling heard were both statistically significantly associated with lower burnout and greater process adaptation. Only psychological safety exhibited a statistically significant relationship with less worsening burnout during crisis. We found evidence that feeling heard mediates psychological safety's relationship to burnout and process adaptation. Psychological safety is important but not sufficient for feeling heard. Feeling heard may help mitigate burnout and enable adaptation during uncertainty. For health care leaders, expanding beyond psychological safety to also establish a feeling of being heard may further reduce burnout and improve care processes.


FGF2 and insulin signaling converge to regulate cyclin D expression in multipotent neural stem cells.
The ex vivo expansion of stem cells is making major contribution to biomedical research. The multipotent nature of neural precursors acutely isolated from the developing central nervous system has been established in a series of studies. Understanding the mechanisms regulating cell expansion in tissue culture would support their expanded use either in cell therapies or to define disease mechanisms. Basic fibroblast growth factor (FGF2) and insulin, ligands for tyrosine kinase receptors, are sufficient to sustain neural stem cells (NSCs) in culture. Interestingly, real-time imaging shows that these cells become multipotent every time they are passaged. Here, we analyze the role of FGF2 and insulin in the brief period when multipotent cells are present. FGF2 signaling results in the phosphorylation of Erk1/2, and activation of c-Fos and c-Jun that lead to elevated cyclin D mRNA levels. Insulin signals through the PI3k/Akt pathway to regulate cyclins at the post-transcriptional level. This precise Boolean regulation extends our understanding of the proliferation of multipotent NSCs and provides a basis for further analysis of proliferation control in the cell states defined by real-time mapping of the cell lineages that form the central nervous system.


Comparison of bone levels after intramuscular administration of cephradine ('Velosef') or flucloxacillin/ampicillin in hip replacement.
Serum and bone levels of antibiotics were measured after the intramuscular injection of either 1 g cephradine or 500 mg flucloxacillin plus 500 mg ampicillin in 48 patients undergoing total hip replacement. The results showed that both regimens produced adequate blood levels, but that the levels after cephradine were higher and more prolonged. Bone levels of cephradine were significantly higher than for flucloxacillin or ampicillin. In half of the patients studied, flucloxacillin bone levels were below the limit of detection in both cancellous and cortical bone samples. In all 24 patients, cortical levels of cephradine were satisfactory for anti-staphylococcal activity although cancellous levels were unsatisfactory in 4 patients. The penetration of the antibiotics was greater into cortical bone than into cancellous bone.


Unsuspected difficult intubation caused by a laryngeal web.
We report a case of unsuspected difficult intubation in an adult caused by laryngeal web formation in the anterior commissure of the larynx. After induction of anaesthesia, most parts of the posterior commissure of the vocal cords were seen clearly at laryngoscopy, but a 7.5-mm internal diameter (id) tracheal tube could not be advanced below the level of the vocal cords because of resistance. Intubation was re-attempted several times after oxygenation by mask with trials of smaller tubes. Finally, a 5.0-mm id cuffed tube was passed successfully through the vocal cords, and secured in place. Because of the unexpected difficulties in intubation, an otolaryngologist was consulted to examine the larynx with a microscope. A web of 0.5 cm in the anterior commissures was found which caused subglottic stenosis.


C-1 lateral mass screw fixation in children with atlantoaxial instability: case series and technical report.
Retrospective cohort study. To evaluate the feasibility, safety, and efficacy of incorporating C-1 lateral mass screws into fusion constructs in children with atlantoaxial instability. The operative treatment of atlantoaxial instability varies widely based on anatomy, patient age, and surgeon preference. The modified Harms construct, consisting of polyaxial C-1 lateral mass screws together with C-2 pedicle or pars screws and rods, has shown satisfactory fusion rates and minimal incidence of complications in adult patients. However, its utility in the pediatric population remains unproven, largely because of the technical challenges and risks inherent in placing C-1 lateral mass screws in children with immature bone quality, extensive anatomical variability, and smaller osseous structures. We retrospectively reviewed the records of all pediatric patients with atlantoaxial instability treated surgically, with a fusion construct incorporating C-1 lateral mass screws, at our institution between July 1, 2005 and June 30, 2008. Eight patients were identified and their relevant clinical data were abstracted from the medical record. All patients had C-1 lateral mass screws placed as part of a fixation construct. Six cases used C-2 pedicle screws and 2 cases used C-3 lateral mass screw fixation for the inferior portion of the construct. There were 6 female and 2 male patients. Age at the time of the surgery ranged from 5 to 13 years (mean 9 y), and follow-up ranged from 11 to 38 months (mean 23 mo). No C-2 nerve root was sacrificed in any patient. There were no intraoperative or postoperative complications, including neurological injury, vascular injury, or hardware-related complications. Successful fusion was documented with dynamic cervical spine radiography in all cases. C-1 lateral mass screw placement is generally feasible and safe in pediatric patients. With a nearly 2-year average follow-up, C1-2 rigid screw/rod fixation has proven to be an effective treatment modality for pediatric atlantoaxial instability in our series.


Tumor proliferative fraction in solid malignant neoplasms. A comparative study of Ki-67 immunostaining and flow cytometric determinations.
Tumor proliferative fraction (TPF) has been shown to correlate with prognosis in some malignancies. A method for its determination that is practical, accurate, and reproducible is still being sought. In this comparative study of techniques, TPF values were determined in mirror-image samples of 126 consecutive solid malignant neoplasms using flow cytometry and immunostaining with Ki-67, a monoclonal antibody that recognizes an unknown nuclear antigen expressed during the entire cell proliferation cycle but not in resting cells. The mean TPF values for all cases were 19.5 +/- 15.6% (percentage of tumor cells stained) by Ki-67 (range, 1-86%) and 15.7 +/- 9.6% (S + G2M) by flow cytometry (range, 3-60%), which correlated significantly at r = 0.53 and P = 0.005. The correlation was less strong in tumors with low S-phase values (less than or equal to 10%, r = 0.28) than in tumors with intermediate and high S-phase values (r = 0.66). Ki-67 staining percentages did not correlate with patient age, sex, or tissue origin of the tumor. Ki-67 staining appears comparable to flow cytometry determination of TPF in solid malignancies with intermediate and high S-phase values. In tumors with low S-phase values, Ki-67 immunostaining shows higher TPF values, which perhaps reflect an increase in the proportion of G1-phase cells or dilutional effect of nonneoplastic cells in the tumors with low proliferative fraction.


Diheteroarylethenes as thermally stable photoswitchable acceptors in photochromic fluorescence resonance energy transfer (pcFRET).
We have employed diheteroarylethenes as acceptors for photochromic FRET (pcFRET), a technique introduced for the quantitative determination of fluorescence resonance energy transfer (FRET). In pcFRET, the fluorescent emission of the donor is modulated by cyclical transformations of a photochromic acceptor. Light induces a reversible change in the structure and, concomitantly, in the absorption properties of the acceptor. Only the closed forms of the selected diheteroarylethenes 2a and 2b have an absorption band overlapping the emission band of the donor, 1. The corresponding variation in the overlap integral (and thus critical transfer distance R(o)) between the two states provides the means for reversibly switching the process of FRET on and off, allowing direct and repeated evaluation of the relative changes in the donor fluorescence quantum yield. The diheteroarylethenes demonstrate excellent stability in aqueous media, an absence of thermal back reactions, and negligible fatigue. The equilibration of these systems after exposure to near-UV or visible light follows simple monoexponential kinetics. We developed a general conceptual scheme for such coupled photochromic-FRET reactions, allowing quantitative interpretations of the photostationary and kinetic data, from which the quantum yields for the cyclization and cycloreversion reactions of the photochromic acceptor were calculated.


Surgical treatment of aorto-iliac artery disease.
In a period of 6 years, up to January, 1980, the author has treated 248 cases of aorto-iliac artery disease. There were 109 cases of abdominal aortic aneurysm, and the remainder was obstructive aorto-iliac artery disease. All but 20% of elective abdominal aortic aneurysms were asymptomatic. There were 100 cases of elective abdominal aortic aneurysm resection with operative mortality of 2%. There were 19 cases of ruptured aortic aneurysm with hospital mortality of 47%. There were 49 cases of aorto-femoral artery bypasses with 6th year cumulative patency rate of 89% in aorto-femoral bypass with Dacron graft, and 69% in aorto-iliac artery bypass with Dacron graft, and 2 year cumulative patency rate of 75% in descending thoracic aorto-femoral artery bypass with Poly Tetra Fluoro Ethylene graft. There were 32 cases of axillo-femoral artery bypasses and 48 cases of femoral-femoral artery bypasses. The 3 year cumulative patency rate of axillo-femoral artery bypass with PTFE graft was 89%, and that of femoral-femoral artery bypass with PTFE was 85%. However, axillo-femoral artery bypass with Dacron graft had 3-year patency rate of 67% and femoral-femoral artery bypass with Dacron graft was 62%. The 4 year cumulative patency rate of axillo-femoral artery bypass with Dacron graft was 39%. The 5 year cumulative patency rate of femoral-femoral artery bypass with Dacron graft was 62%


Surface polaron states on single-crystal rutile TiO2 nanorod arrays enhancing charge separation and transfer.
Polaron states on TiO2 photoanodes provide an important electron transfer pathway at the electrode-electrolyte interface. Here, we electrochemically doped single-crystal rutile TiO2 nanorod arrays with exposed (110) facets to produce surface polaron states, Ti3+-OH, which greatly contributed to charge separation and transfer. Our results experimentally clarified the previously confused understanding of the origin of improved photoelectrochemical (PEC) water splitting performance and verified that the enhanced PEC effects mainly arise from surface polaron states instead of grain boundary passivation.


[Dynamic magnetic resonance of the temporomandibular joint. Observations and findings].
Condylar movements can be executed only if the TMJ morphology can satisfy functional needs of the masticatory apparatus. Articular components have to be in good relation with dento-skeletal functional anatomy: if this does not occur, mandibular dynamics may establish some functional stresses on the condylar head and the articular eminence. These overloaded structures and particularly their functional surfaces react to this situation to be remodelling and deformation of the articular cavity. In our work we have used a new method to analyse condylar dynamics using MRI. The reconstruction of mandibular movements, using this instrumentation, permits to make some useful observations on the functional capability of TMJ to adjust itself to different maxillofacial morphologies and, consequently, how this joint can fall in a dysfunctional and pathological condition.


Preservation of ranking order in the expression of human Housekeeping genes.
Housekeeping (HK) genes fulfill the basic needs for a cell to survive and function properly. Their ubiquitous expression, originally thought to be constant, can vary from tissue to tissue, but this variation remains largely uncharacterized and it could not be explained by previously identified properties of HK genes such as short gene length and high GC content. By analyzing microarray expression data for human genes, we uncovered a previously unnoted characteristic of HK gene expression, namely that the ranking order of their expression levels tends to be preserved from one tissue to another. Further analysis by tensor product decomposition and pathway stratification identified three main factors of the observed ranking preservation, namely that, compared to those of non-HK (NHK) genes, the expression levels of HK genes show a greater degree of dispersion (less overlap), stableness (a smaller variation in expression between tissues), and correlation of expression. Our results shed light on regulatory mechanisms of HK gene expression that are probably different for different HK genes or pathways, but are consistent and coordinated in different tissues.


Thoracoscopy: the preferred approach for the resection of selected posterior mediastinal tumors.
The posterior mediastinum is a common site for neurogenic tumors. These are mostly asymptomatic and detected incidentally during radiologic investigations. However, they occasionally present with compressive or neurologic symptoms. The tumors are mostly benign but can also be malignant. Left untreated, they continue to grow. Therefore, once detected, resection is always advised. Traditionally, resection has been performed by standard posterolateral thoracotomy. More recently, such tumors have been removed thoracoscopically. We report our experience with three such cases and present a comprehensive analysis of cases of thoracoscopic resection of posterior mediastinal neurogenic tumors reported in the English literature to suggest guidelines for their current management.


Concentration-dependent effect of met-enkephalin on human polymorphonuclear leukocytes.
Met-enkephalin in 10(-9)-10(-7)M concentrations exerts an ADCC-stimulating effect on human PMNLs through naloxone-sensitive opiate receptors, elevating the cytoplasmic free Ca2+ and cGMP levels. In higher, 10(-6)-10(-5)M concentrations ME has a cAMP-elevating effect and a rapid 45Ca2+ influx was observed. This latter effect of ME, which is also associated with the suppression of ADCC activity, was abolished by the enkephalinase inhibitor, puromycin. A strong relationship is suggested between the suppressing effect of metenkephalin, enkaphalinase and the protein kinase C system.


Mandibular dysfunction and periodontitis. A comparative study of patients with periodontal disease and occlusal parafunctions.
Fifty-one patients (mean age, 47.3 years) with moderate to severe periodontal disease and 40 patients (mean age, 48.9 years) with symptoms related to bruxism (occlusal parafunctions such as grinding and/or clenching of the teeth) were compared with regard to periodontal conditions and signs and symptoms of mandibular dysfunction. The bruxists reported more symptoms of pain and dysfunction of the masticatory system than the periodontal patients. The clinical dysfunction index was significantly higher among the bruxists, while there was a similarity between the groups in the variation of occlusal conditions, except for occlusal wear, which was more pronounced in the bruxist group. Attrition was in general positively correlated to alveolar bone height. This correlation was stronger (and statistically significant) for the canines than for other teeth. Attrition was negatively correlated to tooth mobility. It is concluded that patients with moderate to severe periodontal disease and patients with bruxism/occlusal parafunctions are distinctly different with regard to signs and symptoms of mandibular dysfunction. The results support the opinions that there is no or only weak correlation between periodontal disease and bruxism, and between bruxism and occlusal status.


Adoption of Internet technology by UK postgraduate centres: a questionnaire survey.
A survey of UK postgraduate centres during September 1997 found that almost 60% were connected to the Internet, but librarians were still the largest user group, few had more than one access point and support to users was limited. Significant progress was made during the following 18 months--by April 1999 all but one of the remaining sites had Internet access in either the postgraduate centre or in a separate library. Lack of funds and decisive policy were stated to be the most common reasons for delay in connecting. The Internet was rated highly as source of the latest research information and support for evidence-based medicine and continuing education. Expansion of the role of librarians to include assistance with sophisticated searches seemed a logical move to the majority, yet the survey suggests that a significant investment in time and money will be required to support the use of the Internet in continuing medical education in the broadest sense. It is likely that the traditional boundaries between IT departments, libraries and user groups will need to be redrawn if the technology is to be exploited effectively.


Oocyte shuttle, a recombinant protein transporting donor DNA into the Xenopus oocyte in situ.
The newly developed oocyte shuttle protein contains a streptavidin moiety that tightly binds biotinylated DNA. Injected intravenously into adult Xenopus females, the protein-DNA complex is rapidly transported through the bloodstream and, within the ovary, the vitellogenin ligand present in the protein binds to the receptors at the surface of the oocytes. The bound complex is internalized and translocates into the oocyte nucleus thanks to an SV40 nuclear localization signal, enhanced by an adjacent casein kinase phosphorylation site. Functioning of the shuttle protein is documented by transporting DNA molecules that, upon intramolecular homologous recombination within the oocyte nucleus, express easily traceable markers such as green fluorescence or tetracycline resistance.