Paralytic poliomyelitis can be eliminated.
Since the introduction and widespread use of inactivated and oral poliovirus vaccines, there has been a continued and increasing commitment to worldwide poliomyelitis control. The eradication of poliomyelitis in certain countries, smallpox eradication worldwide, the World Health Organization's (WHO) Expanded Programme on Immunization, and advances in poliovirus vaccine production augur well for worldwide elimination within the next few decades. The success of any such program rests firmly upon scientific feasibility, intensive epidemiologic surveillance, and economic justification. The development of a variety of disease-specific control/prevention programs worldwide have improved communicable disease reporting in many countries and established health-care infrastructure as well. Equally important has been the emergence of the concept of epidemiologic surveillance. The success of poliomyelitis elimination in large parts of the world, the WHO commitment, and the tragic, visible effects of poliomyelitis are sufficiently strong arguments to persuade the countries of the world to make the necessary effort to eliminate poliomyelitis within the next generation.


The separation, prtial purificatio nd some properties of isoenzymes of aldolase from guinea-pig cerebral cortex.
1. Aldolase isoenzymes from guinea-pig cerebral cortex were partially purified and separated by ammonium sulphate fractionation and chromatography on DEAE-cellulose. 2. Each purified isoenzyme was shown to be virtually uncontaminated with other forms by starch-gel electrophoresis. The quantitative distribution of the isoenzymes was: I, 6.2%; II, 5.2%; III, 15.3%; IV, 25.7%; V, 33.3%. 3. The pH optima for the five separated isoenzymes were similar; all were in the range pH7.5-8.0. Values for pK(a) (6.31-6.55) and pK(b) (9.45-9.59) were calculated from the data and suggested the involvement of histidine and lysine residues. 4. The stabilities of the isoenzymes were shown to be I=II>III>IV>V at pH4.4 in order of decreasing stability and are discussed in terms of subunit structure. 5. The substrate activity ratios (fructose 1,6-diphosphate/fructose 1-phosphate) were measured and all were in the range 12-44.


Increasing the success rate of lantibiotic drug discovery by Synthetic Biology.
Lantibiotics are post-translationally modified antimicrobial peptides produced by bacteria from diverse environments that exhibit an activity against pathogenic bacteria comparable to that of medically used antibiotics. The actual need for new antimicrobials in therapeutics has placed them in the pipeline of antibiotic research, due not only to their high antimicrobial activity but also to the fact that they are directed to novel targets. This review covers the different approaches traditionally used in bacteriocin discovery, based on the isolation of bacteria from different habitats and determining their inhibitory spectrum against a set of relevant strains. It also elaborates on more recent approaches covering organic synthesis and semi-synthesis of lantibiotics, genomic and proteomic approaches and the application of Synthetic Biology to the field of antimicrobial drug discovery. Lantibiotics show a great potential in fulfilling the requirements for new antimicrobials. Culture-dependent techniques are still applied to lantibiotic discovery producing successful results that can be furthered by employing high-throughput screening techniques and peptidogenomics. The necessity of culturing bacteria and growing them in specific conditions for lantibiotic expression, can hamper the discovery rate, especially in exotic or unculturable bacteria. Thus, a combination of genome mining procedures, to detect novel lantibiotic-related sequences, with heterologous production systems and high-throughput screening, offers a promising strategy. Furthermore, the characterization of the mechanism of action of many lantibiotics, and the development of "plug and play" peptide biosynthesis systems, offers the possibility of initiating the rational design of non-natural lantibiotics based on structure-activity relationships.


Antitumor effects of ricin A chain immunotoxins prepared from intact antibodies and Fab' fragments on solid human Hodgkin's disease tumors in mice.
Three monoclonal antibodies which strongly bind to Hodgkin and Reed-Sternberg cells and two corresponding Fab' fragments were linked to deglycosylated ricin A chain (dg A) to evaluate their potential as immunotoxins for the treatment of Hodgkin's disease. Two of the antibodies, Ber-H2 and HRS-3, were shown to bind to the same epitope on the CD30 antigen, whereas the third antibody, IRac, bound to a different antigen. None of the antibodies significantly cross-reacted with normal human tissues as judged by indirect immunofluorescence and immunoperoxidase analyses on frozen sections from 28 normal tissues. All three antibodies formed potent and specific immunotoxins. They inhibited protein synthesis of the L540 Hodgkin's disease cell line in vitro by 50% at concentrations of 1 x 10(-11) M for IRac.dgA, 9 x 10(-11) M for HRS-3.dgA, and 2 x 10(-10) M for Ber-H2.dgA. HRS-3 Fab' and IRac Fab' immunotoxins were 7.8- and 60-fold less cytotoxic, respectively, than their intact counterparts in vitro. In vivo, a single i.v. injection of a dose of Ber-H2.dgA, HRS-3.dgA, or IRac.dgA corresponding to 40% of the LD50 induced lasting complete remissions in 38, 44, and 50%, respectively, of mice with solid s.c. L540 tumors of 60 to 80 mm3 size (0.5-cm diameter). At equivalent dosage (40% of the LD50), the HRS-3 Fab'.dgA and the IRac Fab'.dgA both induced lasting complete remissions in 25% of the mice, although the HRS-3 Fab'.dgA was significantly superior to IRac Fab'.dgA at retarding tumor growth in the remaining animals. The effectiveness of the immunotoxins depended on the size of the tumor at the time of injection, since IRac.dgA treatment induced complete remissions in 100% of mice with small tumors (10 to 20 mm3, approximately 0.3 cm in diameter) but only 13% of mice with larger tumors of 400 to 600 mm3 (approximately 1 cm in diameter). Tumors which regrew after IRac.dgA treatment mainly consisted of antigen-deficient mutants having reduced sensitivity to IRac.dgA but normal sensitivity to HRS-3.dgA. It is concluded that HRS-3.dgA, HRS-3 Fab'.dgA, and IRac.dgA are candidates for the treatment of Hodgkin's disease in humans.


Do management practices support or constrain safe driving behaviour? A multi-level investigation in a sample of occupational drivers.
It has been estimated that one-third of all work-related deaths occur while driving for work-related purposes. Despite this, many organisations are unaware of the practices, beyond those that identify and control the impact of unforeseen events (i.e., risk management), that predispose drivers to risk. This study addresses the issue by identifying the management practices operationalised as, High Performance Workplace Systems (HPWS) that influence safe driver behaviour. The study also explores the value given to safety by senior level management as a moderator of the relationship between HPWS practices and driver behaviour. Each factor was tested within a two level hierarchical model consisting of 911 drivers, nested within 161 supervisors and 83 organisations. The findings highight that under conditions of high investment in job and work design, communication and selection practices, drivers reported poorer driving behaviour. An interaction effect also demonstrated that under conditions of high investment in remuneration, drivers reported safer behaviour, but only when they perceived that managers valued and prioritised safety. The findings challenge current thinking in the management of workplace road safety.


Methyl-N-methylanthranilate, a pungent compound from Citrus reticulata Blanco leaves.
More analgesic compounds are needed in medicine against pain since the available drugs displayed secondary effects. Natural products are a source of molecules to develop new analgesics, using the information of plants, applied against pain, with effects such as pungency, tingling, and needle, due to their possible role in the central nervous system (NCS). Citrus reticulata Blanco (Rutaceae) leaves are usually bitten to flavor the mouth and possess this type effect in lips and tongues; due to this fact the structure of the bioctive compound could be the source of other types of analgesics. The objective of this study is to determine the causal agent of the pungent effect in mandarin essential oil. Mandarin essential oil was obtained and then purified by column chromatography. Each fraction was tested and pungency was detected only in the first fraction which was pure. The compound responsible for the pungency in the essential oils of leaves from Citrus reticulata (mandarin) was purified and the structure was assigned as methyl-N-methylanthranilate, on the basis of NMR 1D and 2D and MS. This substance corresponds to another type of molecule involving an antinociceptive effect. Terpenes are compounds found in essential oils. The compound responsible for the pungency of mandarin and other citrus leaves was isolated, and surprisingly it was identified as a methyl-N-methylanthranilate. This kind of molecules with this activity could be used to discover new analgesics in human therapy against pain.


Red blood cell distribution width as a prognostic marker of mortality in patients on chronic dialysis: a single center, prospective longitudinal study.
To determine if red cell distribution width (RDW) is associated with all-cause mortality in patients on chronic dialysis and to evaluate its prognostic value among validated prognostic biomarkers. This is a single center, prospective longitudinal study. At the time of inclusion in January 2011, all patients were physically examined and a routine blood analysis was performed. A sera sample was preserved for determination of NT-pro-brain natriuretic peptide (NT-pro-BNP) and eosinophil cationic protein. Carotid intima media thickness (IMT) was also measured. Following one year, all-cause mortality was evaluated. Of 100 patients, 25 patients died during the follow-up period of one-year. Patients who died had significantly higher median [range] RDW levels (16.7% [14.3-19.5] vs 15.5% [13.2-19.7], P<0.001. They had significantly higher Eastern Cooperative Oncology Group (ECOG) performance status (4 [2-4] vs 2 [1-4], Plt;0.001), increased intima-media thickness (IMT) (0.71 [0.47-1.25] vs 0.63 [0.31-1.55], P=0.011), increased NT-pro-BNP levels (8300 [1108-35000] vs 4837 [413-35000], P=0.043), and increased C-reactive protein (CRP) levels (11.6 [1.3-154.2] vs 4.9 [0.4-92.9], Plt;0.001). For each 1% point increase in RDW level as a continuous variable, one-year all cause mortality risk was increased by 54% in univariate Cox proportional hazard analysis. In the final model, when RDW was entered as a categorical variable, mortality risk was significantly increased (hazard ratio, 5.15, 95% confidence interval, 2.33 to 11.36) and patients with RDW levels above 15.75% had significantly shorter survival time (Log rank Plt;0.001) than others. RDW could be an additive predictor for all-cause mortality in patients on chronic dialysis. Furthermore, RDW combined with sound clinical judgment improves identification of patients who are at increased risk compared to RDW alone.


[Model selection and curative effect judgment criteria for artificial liver in the treatment of liver failure].
Artificial liver is one of the effective methods to treat liver failure. Patients with liver failure are critically ill and have great individualized differences. Therefore, the specific program for the treatment of liver failure with artificial liver should be individualized. The commonly used non-biological artificial liver models include simple plasmapheresis, double filtration plasmapheresis, plasma filtration with dialysis, double plasma molecular adsorption system, molecular absorbent recirculating system, hemodiafiltration, continuous venovenous hemodiafiltration, hybrid, etc. The curative effect should be properly judged from patient's symptoms, laboratory test indicators, survival rate and other aspects after artificial liver therapy.


Enhancing regulatory T-cell function via inhibition of high mobility group box 1 protein signaling in immune thrombocytopenia.
Primary immune thrombocytopenia (ITP) is the most common acquired autoimmune bleeding disorder. Abnormally increased levels of High Mobility Group Box 1 (HMGB1) protein associate with thrombocytopenia and therapeutic outcome in ITP. Previous studies proposed that a natural inhibitor of HMGB1, 18β-glycyrrhetinic acid (18β-GA), could be used for its anti-inflammatory and immune-modulatory effects, although its ability to correct immune balance in ITP is unclear. In this study, we showed that plasma HMGB1 correlated negatively with platelet counts in ITP patients, and confirmed that 18β-GA stimulated the production of regulatory T cells (Treg), restored the balance of CD4+ T-cell subsets and enhanced the suppressive function of Treg through blocking the effect on HMGB1 in patients with ITP. HMGB1 short hairpin RNA interference masked the effect of 18β-GA in Treg of ITP patients. Furthermore, we found that 18β-GA alleviated thrombocytopenia in mice with ITP. Briefly, anti-CD61 immune-sensitized splenocytes were transferred into severe combined immunodeficient mice to induce a murine model of severe ITP. The proportion of circulating Treg increased significantly, while the level of plasma HMGB1 and serum antiplatelet antibodies decreased significantly in ITP mice along 18β-GA treatment. In addition, 18β-GA reduced phagocytic activity of macrophages towards platelets both in ITP patients and ITP mice. These results indicate that 18β-GA has the potential to restore immune balance in ITP via inhibition of HMGB1 signaling. In short, this study reveals the role of HMGB1 in ITP, which may serve as a potential target for thrombocytopenia therapy.


Having a child diagnosed with cancer: an assessment of values from the mother's viewpoint.
The purpose of this qualitative study was to explore the mother's experience of having a child diagnosed with cancer. Semistructured interview questions, focused specifically on values, provided the foundation for the study. Each of the 9 participants was a mother of a child diagnosed with cancer 30 days prior to participation. Subsequent data were collected from each participant 6 months after the original interview. Using a phenomenological approach for data collection and analyses, themes were uncovered from each interview data set. The initial interviews identified 3 themes: (1) problems accessing the health care system, (2) challenges of family dynamics, and (3) support structures. Each theme persisted in the second interview, with an additional theme, (4) future plans, uncovered. Data from this study may provide guidance for health care professionals who provide care to these children and their families. The importance of maintaining communication and keeping promises cannot be overstated.


A Case of Acquired von Willebrand Syndrome Complicated by Acute Myelomonocytic Leukemia.
We here report a 21-year-old male who presented with acute myelomonocytic leukemia (AMML) associated with acquired von Willebrand syndrome (AVWS). To our knowledge, this is the first case of AVWS caused by AMML. In our case, following remission-induction chemotherapy combined with idarubicin and cytarabine, the patient showed remarkable improvement of bleeding symptoms due to AVWS. Moreover, after an allogeneic stem cell transplantation from a sibling donor, both AMML and AVWS maintain complete remission.


Weakly coupled molecular photonic wires: synthesis and excited-state energy-transfer dynamics.
Molecular photonic wires, which absorb light and undergo excited-state energy transfer, are of interest as biomimetic models for photosynthetic light-harvesting systems and as molecular devices with potential applications in materials chemistry. We describe the stepwise synthesis of four molecular photonic wires. Each wire consists of an input unit, transmission element, and output unit. The input unit consists of a boron-dipyrrin dye or a perylene-monoimide dye (linked either at the N-imide or the C9 position); the transmission element consists of one or three zinc porphyrins affording short or long wires, respectively; and the output unit consists of a free base (Fb) porphyrin. The components in the arrays are joined in a linear architecture via diarylethyne linkers (an ethynylphenyl linker is attached to the C9-linked perylene). The wires have been examined by static absorption, static fluorescence, and time-resolved absorption spectroscopy. Each wire (with the exception of the C9-linked perylene wire) exhibits a visible absorption spectrum that is the sum of the spectra of the component parts, indicating the relatively weak electronic coupling between the components. Excitation of each wire at the wavelength where the input unit absorbs preferentially (typically 480-520 nm) results in emission almost exclusively from the Fb porphyrin. The static emission and time-resolved data indicate that the overall rate constants and quantum efficiencies for end-to-end (i.e., input to output) energy transfer are as follows: perylene-(N-imide)-linked short wire, (33 ps)(-1) and >99%; perylene-(C9)-linked short wire, (26 ps)(-1) and >99%; boron-dipyrrin-based long wire, (190 ps)(-1) and 81%; perylene-(N-imide)-linked long wire, (175 ps)(-1) and 86%. Collectively, the studies provide valuable insight into the singlet-singlet excited-state energy-transfer properties in weakly coupled molecular photonic wires.


Viscoelastic fluid response can increase the speed and efficiency of a free swimmer.
Microorganisms navigate through complex environments such as biofilms and mucosal tissues and tracts. To understand the effect of a complex medium upon their locomotion, we investigate numerically the effect of fluid viscoelasticity on the dynamics of an undulating swimming sheet. First, we recover recent small-amplitude results for infinite sheets that suggest that viscoelasticity impedes locomotion. We find the opposite result when simulating free swimmers with large tail undulations, with both velocity and mechanical efficiency peaking for Deborah numbers near one. We associate this with regions of highly stressed fluid aft of the undulating tail.


A Comparative Pharmacokinetic Study by UHPLC-MS/MS of Main Active Compounds after Oral Administration of Zushima-Gancao Extract in Normal and Adjuvant-Induced Arthritis Rats.
A sensitive and rapid ultra high-performance liquid-chromatography tandem mass spectrometry (UHPLC-MS/MS) method has been applied to investigate the influence of rheumatoid arthritis (RA) on the pharmacokinetics of nine analytes (daphnetin, daphnoretin, 7-hydroxycoumarin, liquiritin, isoliquiritin, liquiritigenin, isoliquiritigenin, glycyrrhizin, and glycyrrhetinic acid), which are major active components in Zushima-Gancao extract. The analytes and internal standard (IS) were separated in a Hypersil Gold C18 column and detected on a triple-stage quadrupole mass spectrometer using the validated method. All analytes exhibited good linearities (R² > 0.98), and the lower limit of quantification (LLOQs) were sufficient for quantitative analysis. Intra- and inter-batch precision were all within 14.96% while the accuracy of nine analytes ranged from -17.99 to 14.48%, and these results were all within acceptance criteria. The extraction recoveries, matrix effects, and stabilities were all satisfactory. Main pharmacokinetic parameters of each compound were compared, and significant differences were found in parameters of daphnetin, daphnoretin, liquiritin, isoliquiritin, isoliquiritigenin, glycyrrhizin, and glycyrrhetinic acid, especially the last one, between the two groups. Therefore, adjuvant-induced arthritis has different effects on the pharmacokinetics of ingredients in Zushima-Gancao extract. The comparative pharmacokinetic study between normal and adjuvant-induced arthritis rats might provide more comprehensive information to guide the clinical usage of Zushima-Gancao extract for treating RA.


Comparison of swimming capacity and energetics of migratory European eel (Anguilla anguilla) and New Zealand short-finned eel (A. australis).
The spawning migration of the European eel (Anguilla anguilla) can cover more than 6000 km, while that of the New Zealand short-finned eel (A. australis) is assumed to be approximately 3000 km. Since these species are expected to show adaptive traits to such an important lifetime event, we hypothesized differences in swimming capacity and energetics as a response to this adaptation. In an experimental swimming respirometer set-up, critical swimming speed (Ucrit), optimal swimming speed (Uopt), mass specific oxygen consumption rate (ṀO2), standard metabolic rate (SMR), active metabolic rate at Ucrit (AMRcrit) and at Uopt (AMRopt), the minimum cost of transport at Uopt (COTmin), and the scope for activity, were assessed and compared between the species. With a similar body length and mass, European eels showed ca. 25% higher values for both Ucrit and Uopt, and 23% lower values for COTmin, compared to New Zealand short-finned eels. However, SMR, AMRcrit, AMRopt, and scope for activity did not differ between the species, indicating very similar swimming physiology traits. This study discusses physiological aspects of long distance migration and provides recommendations for (a) swimming respirometry in anguilliform fish, and (b) telemetry research using externally attached pop-up tags.


Histone H3 variants specify modes of chromatin assembly.
Histone variants have been known for 30 years, but their functions and the mechanism of their deposition are still largely unknown. Drosophila has three versions of histone H3. H3 packages the bulk genome, H3.3 marks active chromatin and may be essential for gene regulation, and Cid is the characteristic structural component of centromeric chromatin. We have characterized the properties of these histones by using a Drosophila cell-line system that allows precise analysis of both DNA replication and histone deposition. The deposition of H3 is restricted to replicating DNA. In striking contrast, H3.3 and Cid deposit throughout the cell cycle. Deposition of H3.3 occurs without any corresponding DNA replication. To confirm that the deposition of Cid is also replication-independent (RI), we examined centromere replication in cultured cells and neuroblasts. We found that centromeres replicate out of phase with heterochromatin and display replication patterns that may limit H3 deposition. This confirms that both variants undergo RI deposition, but at different locations in the nucleus. How variant histones accomplish RI deposition is unknown, and raises basic questions about the stability of nucleosomes, the machinery that accomplishes nucleosome assembly, and the functional organization of the nucleus. The different in vivo properties of H3, H3.3, and Cid set the stage for identifying the mechanisms by which they are differentially targeted. Here we suggest that local effects of "open" chromatin and broader effects of nuclear organization help to guide the two different H3 variants to their target sites.


The value of health care--a matter of discussion in Germany.
Interest in assessing the value of health-care services in Germany has considerably increased since the foundation of the Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen, IQWiG (Institute for Quality and Efficiency in Health Care). The practical application of value assessment illustrates how problematic the process can be. In all decisions made for the provision of health care, data concerning the measurable dimensions (quantity and quality of efficacy and effectiveness, validity of the results and costs) flow into a complex and not yet standardized decision-making process concerning public financing. Some of these decisions are based on data of uncertain validity, unknown reproducibility and unclear appropriateness. In this paper we describe the theoretical aspects of value from psychological and economic viewpoints and discuss national and international approaches. Methodic details and difficulties in assessing the value of health-care services are analysed. A definition of the intangible value of health-care services will be proposed which contains only three factors: the absolute risk reduction (usually a measure of efficacy), the validity of the scientific papers examined and the type of the expected effectiveness (prevention of death and disability, restitution of well-being). The intangible value describes the additional benefit when comparing two possible actions, like treatment or observation only. The description of intangible value from the viewpoint of different stakeholders is a useful measure for subsequent steps (not discussed here) - the evaluation of costs and of patient benefit. A standardised, transparent, fair and democratic evaluation is essential for the definition of a basic benefit package.


Single-tooth implant placement and loading in fresh and regenerated extraction sockets. Five-year results: a case series using two different implant designs.
Implant-supported restorations are a commonly used treatment modality. However, insufficient data are available that compare treatment outcomes of implant restorations using different protocols. Similarly, data comparing the treatment outcomes of different implant designs are limited. This retrospective, non-randomized study evaluates 241 single implants in 241 patients (127 males and 114 females; mean age: 49.3 years; range: 45 to 75 years). Tapered-type (TAP; n = 118) and cylindric screw-type (CYL; n = 123) implants were used. Implants were grouped into the treatment categories of immediate placement, delayed placement, immediate non-occlusal loading, and delayed loading. Clinical parameters, including clinical attachment level (CAL), plaque index (PI), and bleeding on probing (BOP), were recorded at examinations at baseline (BSL) and 1 (E1), 3 (E3), and 5 years (E5) after loading with the final restoration. Eleven implants were lost (five CYL and six TAP). CAL and PI outcomes were similar for both implant types. No significant influence of implant position was found. A CAL loss of 1.5 mm was observed during the first 3 years. The type of implant and timing of placement showed no significant influence on the survival rate, whereas the failure rate was lower for immediate non-occlusal loaded implants. The type of implant, position, and timing of placement and loading did not influence the survival rate of this treatment method.


Role of itraconazole metabolites in CYP3A4 inhibition.
Itraconazole (ITZ) is a potent inhibitor of CYP3A in vivo. However, unbound plasma concentrations of ITZ are much lower than its reported in vitro Ki, and no clinically significant interactions would be expected based on a reversible mechanism of inhibition. The purpose of this study was to evaluate the reasons for the in vitro-in vivo discrepancy. The metabolism of ITZ by CYP3A4 was studied. Three metabolites were detected: hydroxy-itraconazole (OH-ITZ), a known in vivo metabolite of ITZ, and two new metabolites: keto-itraconazole (keto-ITZ) and N-desalkyl-itraconazole (ND-ITZ). OHITZ and keto-ITZ were also substrates of CYP3A4. Using a substrate depletion kinetic approach for parameter determination, ITZ exhibited an unbound K(m) of 3.9 nM and an intrinsic clearance (CLint) of 69.3 ml.min(-1).nmol CYP3A4(-1). The respective unbound Km values for OH-ITZ and keto-ITZ were 27 nM and 1.4 nM and the CLint values were 19.8 and 62.5 ml.min(-1).nmol CYP3A4(-1). Inhibition of CYP3A4 by ITZ, OH-ITZ, keto-ITZ, and ND-ITZ was evaluated using hydroxylation of midazolam as a probe reaction. Both ITZ and OH-ITZ were competitive inhibitors of CYP3A4, with unbound Ki (1.3 nM for ITZ and 14.4 nM for OH-ITZ) close to their respective Km. ITZ, OH-ITZ, keto-ITZ and ND-ITZ exhibited unbound IC50 values of 6.1 nM, 4.6 nM, 7.0 nM, and 0.4 nM, respectively, when coincubated with human liver microsomes and midazolam (substrate concentration < Km). These findings demonstrate that ITZ metabolites are as potent as or more potent CYP3A4 inhibitors than ITZ itself, and thus may contribute to the inhibition of CYP3A4 observed in vivo after ITZ dosing.


Pivotal advance: inhibition of HMGB1 nuclear translocation as a mechanism for the anti-rheumatic effects of gold sodium thiomalate.
Gold compounds such as gold sodium thiomalate (GST) can reduce the symptoms of rheumatoid arthritis (RA), although their mechanism of action is not well defined. As the proinflammatory mediator high mobility group box chromosomal protein 1 (HMGB1) may play a role in the pathogenesis of RA, we have performed in vitro studies to investigate whether GST inhibits HMGB1 release as the basis of its mode of action. Murine RAW 264.7 or human THP-1 macrophage cells were stimulated in culture with agents causing extracellular HMGB1 release, including LPS, IFN-gamma, polyinosinic:polycytidylic acid, IFN-beta, or NO in the presence of GST, ranging from 0 microM to 250 microM. Secretion and intracellular location of HMGB1 were assessed by Western blotting, HMGB1-specific ELISPOT assay, and immunofluorescent staining. In parallel, TNF and IFN-beta levels were analyzed by ELISPOT and/or ELISA. Supernatant NO production was analyzed by the Griess method. At pharmacologically relevant doses, GST inhibited the extracellular release of HMGB1 from activated macrophages and caused the nuclear retention of this protein; in contrast, no effects were observed on the secretion or production of TNF. Release of the key endogenous mediators of HMGB1 translocation, IFN-beta and NO, was inhibited by GST. This inhibition required gold, as sodium thiomalate did not affect the responses measured. Furthermore, gold chloride also inhibited release of HMGB1. Together, these results suggest a new mechanism for the anti-rheumatic effects of gold salts in RA and the potential of drugs, which interfere with intracellular HMGB1 transport mechanisms, as novel agents to treat RA.


[Reactor neutron activation analysis for aluminium in the presence of phosphorus and silicon. Contributions of 28Al activities from 31P(n, alpha) 28Al and 28Si(n, p) 28Al reactions].
Reactor neutron activation analysis for aluminium in samples containing phosphorus and silicon was studied. The experiments were performed by using neumatic tube of the Kyoto University Reactor (KUR). At first, the ratios of the 28Al activity produced from 27Al(n, gamma) 28Al reaction by thermal neutrons to that from 31P(n, alpha) 28Al reaction by fast neutrons, and to that from 28Si(n, p) 28Al reaction were measured by gamma-ray spectrometry. With a ratio of about 5 for the thermal to fast neutron flux of KUR, the ratio of the 28Al activity from aluminium to that from phosphorus was to be 812 +/- 7, and to that from silicon 282 +/- 3. Secondly, the contributions of 28Al activities from phosphorus and silicon and the determination limit of aluminium were calculated for various parameters, such as fast neutron flux, thermal to fast neutron flux ratio, amounts of phosphorus and silicon, etc. Thirdly, on the basis of these results, aluminium contents in spinal cords and brains of amyotrophic lateral sclerosis, Parkinsonism-dementia complex and control cases were determined.


MK-0457, a novel kinase inhibitor, is active in patients with chronic myeloid leukemia or acute lymphocytic leukemia with the T315I BCR-ABL mutation.
MK-0457 (VX-680) is a small-molecule aurora kinase (AK) inhibitor with preclinical antileukemia activity. The T315I BCR-ABL mutation mediates resistance to imatinib, nilotinib, and dasatinib. MK-0457 has in vitro activity against cells expressing wild-type or mutated BCR-ABL, including the T315I BCR-ABL mutation. Three patients with T315I abl-mutated chronic myeloid leukemia (CML) or Philadelphia chromosome (Ph)-positive acute lymphocytic leukemia (ALL) have achieved clinical responses to doses of MK-04547 that are not associated with adverse events. Higher MK-0457 dose levels were associated with clinical responses and down-regulation of CrkL phosphorylation in leukemia cells. The possible role of AK inhibition in these clinical responses requires further investigation. The currently reported cases are the first observed clinical activity of a kinase inhibitor against the T315I phenotype. The observation of responses in 3 patients with T315I phenotype-refractory CML or Ph-positive ALL, at doses of MK-0457 associated with no significant extramedullary toxicity, is very encouraging.


Collagenous fibril texture of the human knee joint menisci.
Anatomical and clinical literature describes the arrangement of collagen fibrils in the human meniscus as being "arcade-like". The "arcade-like" orientation, mainly running in a radial direction in the internal circumference and in a circular direction in the external circumference, was found in polarization light microscopic studies. This, however, does not provide a mechanical explanation for the direction of meniscus tears. In view of this contradiction collagen fibrils in the menisci of adults aged from 18 to 85 years were exposed layer-by-layer to study their arrangement by scanning electron microscopy. The results obtained by this procedure were compared to the path of the split lines. Scanning electron microscopy reveals three distinct layers in the meniscus cross section: (1) The tibial and femoral sides of the meniscus surfaces are covered by a meshwork of thin fibrils with a diameter of approximately 30 nm. (2) Beneath the superficial network there is a layer of lamellalike collagen fibril bundles on the tibial and femoral surface. In the area of the external circumference of the anterior and posterior segments the bundles of collagen fibrils are arranged in a radial direction. In all other parts the collagen fibril bundles intersect at various angles. (3) The main portion of the meniscus collagen fibrils are located in the central region between the femoral and the tibial surface layers. Everywhere in the central main portion of the meniscus the bundles of collagen fibrils are orientated in a circular manner. The split lines in the region of the internal circumference of the menisci are arranged in a circular manner, generally running in a radial direction in the portions adjacent to the base. Scanning electron microscopy reveals that the direction of the split lines depends on the orientation of the collagen fibrils in the superficial lamellar layer. The arcade-like path of the collagen fibrils described in the literature can not be confirmed either by scanning electron microscopy or by the course of the split lines. The circular arrangement of collagen fibrils in the central portion of the meniscus provides a functional explanation for the longitudinal orientation of the majority of tears in the meniscus tissue.


Increased serine phosphorylation and activation of STAT1 by oncogenic Ras transfection.
Interferon (IFN)-gamma induces the activation of a signal transducer and activator of transcription 1 (STAT1), and regulates the growth response of diverse cell types. Although STAT1 activation is primarily induced upon tyrosine phosphorylation by Jak1 and Jak2 (the IFN-gamma receptor-associated tyrosine kinases), the full activation of STAT1 is thought to involve serine phosphorylation by unidentified protein kinases. As a part of our on-going investigation on the deregulation of STATs in oncogene-transformed cells, we found that STAT1 activation was efficiently induced by IFN-gamma in oncogenic Ras-transformed fibroblasts, compared to the parental fibroblasts. This was shown by target DNA binding activity, nuclear translocation, and tyrosine phosphorylation of STAT1. Using a transient transfection system, we directly demonstrated that Ras-transfection up-regulated the IFN-y-induced STAT1 activation with a concomitant increase in Erk MAPK activity. Notably, the enhanced serine phosphorylation of STAT1 was observed upon Ras-transfection, which was specifically associated with the induction of MAPK, but not Akt activity in these cells. The data suggest that Ras/MAPK module components may positively regulate STAT1 activity by inducing the serine-phosphorylation of STAT1. This would contribute to the enhanced tyrosine phosphorylation, nuclear translocation, and DNA-binding of STAT1 upon exposure of the cells to IFN-gamma in the Ras-transformed cells.


Health trends among college freshmen.
Trends in college student health based on an annual survey of college freshmen administered for 30 consecutive years (1966-1995) at colleges and universities nationwide are described. Trends in the following areas are covered: (1) alcohol and drugs, (2) physical health, (3) psychological health, and (4) sexual attitudes. Gender and institutional differences in health behaviors and attitudes among the 1995 class of college freshmen are also considered. Major trends include declines in beer drinking and in physical and emotional self-confidence and an increase in stress and cigarette smoking. "Unhealthy" behaviors and attitudes are reported most often by freshmen at public 2-year institutions.


Radiographic, macroscopic, and microscopic changes in growth plates of calves raised on hard flooring.
The effect of flooring on the development of physeal and metaphyseal lesions of the limbs was studied in 1- to 5-month-old dairy calves. Calves were allotted to 2 groups. Group I was housed on a clay floor throughout the study and group II was housed on metal slats until weaned and then on concrete. Radiographs of the right thoracic limb of the animals were made 7 times during the experimental period and of the right thoracic and pelvic limbs at necropsy. Selected sections of the physeal regions of the distal part of the radius, metacarpus, metatarsus, and rib were examined microscopically. The physes of the limbs in the 2 groups had eosinophilic streaks and patches which originated in the germinal zone and were associated with blood vessels. These foci varied from small streaks parallel to the chondrocyte columns to multiple horizontal branching patches in which cleft formation and necrosis interrupted the physis, resulting in osseous bridging. Remnants of necrotic cartilage or cartilage containing hypertrophied chondrocytes were located in the metaphysis adjacent to the areas of physeal disruption. Multiple undulations of the physes with variations in thickness and orientation of the chondrocyte columns occurred in the physes of all limbs examined. These areas did not interrupt the physis and were not associated with metaphyseal lesions. The ribs in both groups had focal areas of failure of endochondral ossification characterized by elongation of the hypertrophied zone, accumulation of fibrin and hemorrhage in the zone of provisional calcification, and retention of cartilage within the metaphysis.(ABSTRACT TRUNCATED AT 250 WORDS)


Evaluation of Episiotomy Characteristics of EPISCISSORS-60 Scissors Compared with Mayo Scissors: A Single-Blind Randomized Clinical Trial.
It seems that angled scissors may be able to minimize the occurrence of obstetric anal sphincter injuries (OASIS) during vaginal delivery by correcting the angle of the episiotomy incision.For this purpose, this study aimed to evaluate the episiotomy characteristics of EPISCISSORS-60 scissors compared with Mayo scissors. In this single-blind clinical trial study, 64 pregnant women candidates for natural childbirth were included; 32 women underwent episiotomy with Mayo scissors and 32 underwent episiotomy with the EPISCISSORS-60 instrument. Then, post-suturing angle, incision length, episiotomy, postpartum pain, bleeding volume, and the incidence of OASIS and dyspareunia were assessed. The collected data were analyzed by independent sample t test, chi-square test, and the Fisher exact test. Episiotomy incision length in the EPISCISSORS-60 group with a mean of 4.75 ± 0.72 cm was significantly longer than the Mayo group with a mean of 3.91 ± 0.52cm (P < 0.001). In addition, the incidence of dyspareunia was not significantly different between the 2 groups (6.3% vs 15.6%; P = 0.426). Sphincter damage did not occur at all in the EPISCISSORS-60 group and only 2 cases of grade 3 sphincter rupture occurred in the Mayo group (P = 0.238). The mean of post suturing angle in the EPISCISSORS-60 group (59.09° ± 3.47°) was significantly higher than the Mayo group, with a mean of 31.06° ± 7.21° (P < 0.001). According to the results of the present study, the use of EPISCISSORS-60 can be associated with a higher post-suture episiotomy angle compared with Mayo scissors. As a result, both the incidence of OASIS and its long-term side effects, like dyspareunia, were decreased. However, in our study, the incidence of these complications was very rare and not different between the 2 groups.


Application of physical organic chemistry to engineered mutants of proteins: Hammond postulate behavior in the transition state of protein folding.
Transition states in protein folding may be analyzed by linear free-energy relationships (LFERs) analogous to the Brønsted equation for changes in reactivity with changes in structure. There is an additional source of LFERs in protein folding: the perturbation of the equilibrium and rate constants by denaturants. These LFERs give a measure of the position of the transition state along the reaction coordinate. The transition state for folding/unfolding of barnase has been analyzed by both types of LFERs: changing the structure by protein engineering and perturbation by denaturants. The combination has allowed the direct monitoring of Hammond postulate behavior of the transition state on the reaction pathway. Movement of the transition state has been found and analyzed to give further details of the order of events in protein folding.


Biological properties of peripheral blood progenitor cells mobilized by cyclophosphamide and granulocyte colony-stimulating factor.
Patients transplanted with mobilized blood progenitor cells (PBPC) recover their neutrophil counts more rapidly than patients transplanted with bone marrow even when they receive the same dose/kg of granulocyte-macrophage colony-forming cells (CFU-GM). Here we have sought a biological explanation for this phenomenon. Most CD34-positive PBPC are quiescent (<1% in S phase) when they are collected from the bloodstream of patients treated with cyclophosphamide and granulocyte colony-stimulating factor (G-CSF), but we have shown that they are able to resume proliferation rapidly in vitro by measuring the kinetics of CFU-GM production by primitive plastic-adherent (Pdelta) cells. Also, Pdelta cells in PBPC harvests, unlike normal marrow Pdelta cells, were insensitive to cell-cycle restraint imposed by contact with marrow-derived stromal cells. We found that Pdelta cells in PBPC collections produce relatively more CFU-GM and relatively fewer BFU-E than Pdelta cells in bone marrow, indicating that granulopoiesis might occur at the expense of erythropoiesis, but we were unable to find any differences in the kinetics of granulocytic maturation between PBPC and bone marrow. Our interpretation of these findings is that transplanted PBPC rapidly enter the cell cycle and contact with stromal cells in the marrow does not reduce the proportion of progenitors participating in neutrophil production. Consequently. neutrophil recovery after PBPC infusion is more rapid than neutrophil recovery after marrow infusion. Granulopoiesis at the expense of erythropoiesis may also contribute to this effect.


Characteristics of vestibular function and static balance skills in deaf children.
The vestibular function and static balance skills of 34 children who had sensorineural deafness, ranged in age from 5 to 9 years, and attended the Western Pennsylvania School for the Deaf were compared with normative data. The purpose of the investigation was to describe the characteristics of vestibular function and static balance skill in deaf children who had no other known handicaps. We explored the relationship between these two characteristics. The Southern California Postrotary Nystagmus test and the Standing Balance subtests (eyes open and closed) of the Southern California Sensory Integration tests were used to evaluate the deaf children. Comparison of study results with norms revealed a significant difference in duration of postrotary nystagmus between hearing and deaf children. Balance skills were not significantly related to level of vestibular response. No significant sex differences were found in the vestibular or balance status of the deaf children. The differences in the characteristics of vestibular function and static balance skills in the deaf children compared with hearing children are important to therapists working with the deaf. Therapists should consider that these differences exist when they identify those deaf children with learning or other sensory-motor problems. Therapists familiar with the use of the Southern California Sensory Integration tests and Southern California Postrotary Nystagmus test must be cautious in using these tests with the deaf until they are standardized for this group.


Contamination of the visors of total body exhaust suits in total hip replacement surgery.
We examined 40 visors, used with the Charnley helmets and the total body exhaust suits, for contamination with blood, fat, or washout fluids during primary and revision total hip arthroplasty. All visors showed droplet contamination. This was more extensive in revision surgery (55 droplets: mean) than in primary operations (20 droplets: mean). Surgeons undertaking total hip arthroplasty must have full-face cover. (Hip International 2004; 14: 193-5).


The transvaginal hybrid NOTES versus conventionally assisted laparoscopic sigmoid resection for diverticular disease (TRANSVERSAL) trial: study protocol for a randomized controlled trial.
Natural orifice transluminal endoscopic surgery (NOTES) is the consequence of further development of minimally invasive surgery to reduce abdominal incisions and surgical trauma. The potential benefits are expected to be less postoperative pain, faster convalescence, and reduced risk for incisional hernias and wound infections compared to conventional methods. Recent clinical studies have demonstrated the feasibility and safety of transvaginal NOTES, and transvaginal access is currently the most frequent clinically applied route for NOTES procedures. However, despite increasing clinical application, no firm clinical evidence is available for objective assessment of the potential benefits and risks of transvaginal NOTES compared to the current surgical standard. The TRANSVERSAL trial is designed as a randomized controlled trial to compare transvaginal hybrid NOTES and laparoscopic-assisted sigmoid resection. Female patients referred to elective sigmoid resection due to complicated or reoccurring diverticulitis of the sigmoid colon are considered eligible. The primary endpoint will be pain intensity during mobilization 24 hours postoperatively as measured by the blinded patient and blinded assessor on a visual analogue scale (VAS). Secondary outcomes include daily pain intensity and analgesic use, patient mobility, intraoperative complications, morbidity, length of stay, quality of life, and sexual function. Follow-up visits are scheduled 3, 12, and 36 months after surgery. A total sample size of 58 patients was determined for the analysis of the primary endpoint. The confirmatory analysis will be performed based on the intention-to-treat (ITT) principle. The TRANSVERSAL trial is the first study to compare transvaginal hybrid NOTES and conventionally assisted laparoscopic surgery for colonic resection in a randomized controlled setting. The results of the TRANSVERSAL trial will allow objective assessment of the potential benefits and risks of NOTES compared to the current surgical standard for sigmoid resection. The trial protocol was registered in the German Clinical Trials Register ( DRKS00005995) on March 27, 2014.


[Mealtime support for patients with eating disorders: a survey on the clinical practice in German eating disorders centers].
Mealtime support is a cornerstone of eating disorders (ED) inpatient and day-care treatment but has received only little attention in research so far and no valid recommendations are available for this type of intervention. Thus, the aim of the present study was to gather a comprehensive picture of how mealtime support is currently practiced in Germany. In a nationwide survey, 97 staff members from 66 ED centers across Germany completed a survey-form that covered 4 broad topics: (a) setting, (b) general conditions, (c) specific interventions, and (d) treatment providers' perspective. For the most part, mealtime support is delivered by nurses. Two thirds of the centers provide at least one therapeutically supported meal per day. Most centers offer their patients a kitchen and/or a guided cooking group. Patient eating behavior and amount of food eaten is documented by three quarters of staff members. Most staff members offer some kind of role modeling by eating their own meals at the same table. Food exposure is provided by a minority. Whereas two thirds use sanctions when patients did not achieve their eating goals, only one third use positive reinforcement when patients achieved their goals. Less than one half offer some kind of post-meal support. The results provide important insights into the current practice of mealtime support and will thus inform future studies that examine the efficacy of different types and interventions of mealtime support.


Tahibacter caeni sp. nov., isolated from activated sludge.
A Gram-reaction-negative, aerobic, rod-shaped, non-spore-forming, non-motile bacterial strain, designated BUT-6(T), was isolated from activated sludge of a wastewater-treatment facility. The strain grew at 15-35 °C (optimum 30 °C), pH 4.0-10.0 (optimum pH 7.0) and 0-3.0 % (w/v) NaCl (optimum 1.0 %). Phylogenetic analysis based on 16S rRNA sequences showed that strain BUT-6(T) was most closely related to Tahibacter aquaticus PYM5-11(T) (98.6 % similarity). However, the DNA-DNA relatedness between strain BUT-6(T) and T. aquaticus PYM5-11(T) was 47.1 %. The major fatty acids (>10 % of total fatty acids) of strain BUT-6(T) were iso-C15 : 0, iso-C17 : 1ω9c and iso-C17 : 0. The major respiratory quinone was ubiquinone Q-8. The profile of polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylmethylethanolamine, an unidentified aminophospholipid, three unknown aminolipids and unidentified phospholipids. The DNA G+C content of strain BUT-6(T) was 71.7 mol%. On the basis of the data from the polyphasic taxonomic study presented, strain BUT-6(T) is considered to represent a novel species of the genus Tahibacter, for which the name Tahibacter caeni sp. nov. is proposed. The type strain is BUT-6(T) ( = CCTCC AB 2013266(T) = KACC 17139(T)).


Polyetheretherketone development in bone tissue engineering and orthopedic surgery.
Polyetheretherketone (PEEK) has been widely used in the medical field as an implant material, especially in bone tissue engineering and orthopedic surgery, in recent years. This material exhibits superior stability at high temperatures and is biosecured without harmful reactions. However, the chemical and biological inertness of PEEK still limits its applications. Recently, many approaches have been applied to improve its performance, including the modulation of physical morphology, chemical composition and antimicrobial agents, which advanced the osteointegration as well as antibacterial properties of PEEK materials. Based on the evolution of PEEK biomedical devices, many studies on the use of PEEK implants in spine surgery, joint surgery and trauma repair have been performed in the past few years, in most of which PEEK implants show better outcomes than traditional metal implants. This paper summarizes recent studies on the modification and application of biomedical PEEK materials, which provides further research directions for PEEK implants.


Update on screening and clinical diagnosis of meticillin-resistant Staphylococcus aureus (MRSA).
Based on the failure of conventional control strategies, some experts and public health officials have promoted active screening to detect asymptomatic carriers of meticillin-resistant Staphylococcus aureus (MRSA) as an effective prevention strategy. Data regarding the (cost-) effectiveness of MRSA screening have recently grown and have produced mixed results. Several clinical studies have not only provided conflicting findings but have also raised numerous issues about the appropriate populations for universal versus targeted screening, screening method(s) and intervention(s). It must also be emphasised that screening alone is not effective. Results should be followed by appropriate interventions to reduce the risk of MRSA transmission and infection. We believe a reasonable approach in most European hospitals with an MRSA on-admission prevalence of <5% is to use targeted rather than universal screening (predominantly with chromogenic media, except for high-risk units and critically ill patients for whom molecular tests could be cost effective), after carefully considering the local MRSA epidemiology, infection control practices and vulnerability of the patient population. This strategy is likely to be cost effective if linked to prompt institution of control measures.


Activation of the flavoprotein domain of gp91phox upon interaction with N-terminal p67phox (1-210) and the Rac complex.
A series of truncated forms of His(6)-tagged gp91phox were expressed, solubilized, and purified in the presence of 30 microM FAD. The truncated gp91phox with the longest sequence in the C-terminal region (221-570) (gp91C) showed the highest activity (turnover rate, 0.92) for NADPH diaphorase in the presence of either 0.3% Triton X-100 or 0.5% Genapol X-80. Activity was not inhibited by superoxide dismutase but was blocked by an inhibitor of the respiratory burst oxidase, diphenylene iodonium. The flavinated gp91C contained approximately 0.9 mol of FAD/mol of protein (MW 46 kDa) and 12% alpha-helix content. In the absence of p47phox, p67phox showed considerable activation of gp91C in the presence of Rac. Carboxyl-terminal truncated p67phox (1-210) (p67N), which is the minimal active fragment, was fused with Rac or Q61LRac. The fusion protein p67N-Rac (or p67N-Q61LRac) showed a 2-fold higher stimulatory effect on NBT reductase activity of gp91C than the combination of the individual cytosolic p67N and Rac proteins. In contrast, Rac-p67N, a fusion with the opposite orientation, showed a smaller significant effect on the enzyme activity. The EC(50) values for p67phox, p67N, p67N-Rac, and Rac-p67N were 8.00. 4.35, 2.56, and 15.2 microM, respectively, while the K(m) value for NADPH in the presence and absence of the cytosolic components was almost the same (40-55 microM). In the presence of Rac, p67N or p67phox bound to gp91C with a molar ratio of approximately 1:1 but neither p67N nor Rac alone showed significant binding.


Genetic and phenotypic characterization of a Pseudomonas aeruginosa population with high frequency of genomic islands.
Various genomic islands, PAPI-1, PAPI-2, PAGI-1, PAGI-2, PAGI-3, and PAGI-4, and the element pKLC102 have been characterized in different P. aeruginosa strains from diverse habitats and geographical locations. Chromosomal DNA macroarray of 100 P. aeruginosa strains isolated from 85 unrelated patients hospitalized in an intensive care unit was created to assess the occurrence of these genomic islands (GEIs). The macroarray was then hybridized with labeled probes derived from each genomic island. In addition, PFGE patterns with SpeI, frequency of virulence genes, and antimicrobial resistance patterns of the strains were studied. Our results showed that almost all P. aeruginosa strains presented up to eight virulence genes. By SpeI macrorestriction fragment analysis we were able to identify 49 restriction patterns; 35 patterns correspond to single strains and the remaining 14 to strains subgroup (a-n). Most of the strains showed variation in number or composition of GEIs and a specific antimicrobial pattern indicating that each strain was an unrelated isolate. In terms of the number of genomic islands per strain, 7 GEIs were found in 34% of the strains, 6 in 18%, 5 in 12%, 4 in 14%, 3 in 10%, 2 in 7%, and 1 in 4%; only one isolate did not present any GEI. The genomic islands PAPI-1 and PAPI-2 and the element pKLC102 were the most frequently detected. The analysis of the location of each GEI in the chromosome of two strains show that the islands PAGI-3, PAPI-1, PAPI-2 and pKLC102 are present in the insertion site previously reported, but that PAGI-2 and PAGI-4 are inserted in another chromosome place in a site not characterized yet. In conclusion our data show that P. aeruginosa strains exhibited an epidemic population structure with horizontal transfer of DNA resulting in a high frequency of GEIs.


Incidence, clinical features and epidemiology of rotavirus gastro-enteritis in hospitalized children.
Two hundred and eighteen patients with acute gastro-enteritis (GE) and 67 controls (patients admitted during the period of study for illness other than (GE) were included in this study. Their stool samples were subjected to the following tests to detect the presence of rotavirus: enzyme-linked immunosorbent assay (ELISA), latex agglutination and electron microscopy. Samples positive by any one or more of the above methods were considered positive for rotavirus and were subjected to polyacrylamide gel electrophoresis of viral RNA. Rotavirus was detected in 59 (27.1%) of the 218 GE samples and four (6%) of the control samples. ELISA was the most sensitive test and could detect viral antigen long after the other methods failed to do so.


[The practice guideline 'Otitis externa' (first revision) from the Dutch College of General Practitioners; a response from the perspective of otorhinolaryngology].
The first revision of the practice guideline 'Otitis externa' from the Dutch College of General Practitioners describes diagnostic, therapeutic and preventive aspects of care and focuses mainly on the acute form of the disease. In comparison with the previous guideline, some modest but valuable improvements have been made with regard to diagnosis and medical treatment. For acute otitis externa, treatment with acid and corticosteroid eardrops is considered the treatment of choice, rather than treatment with acid eardrops only. The guideline clearly discusses indications for referral of patients with otitis externa to an otorhinolaryngologist. Hypersensitivity and more severe pathology should be excluded in persistent cases. For chronic otitis externa, an otorhinolaryngologist can provide surgical treatment with a good chance of success and a low recurrence rate.


Cesarean delivery is not associated with decreased at-birth fracture rates in osteogenesis imperfecta.
Osteogenesis imperfecta (OI) predisposes to recurrent fractures. Patients with the moderate to severe forms of OI present with antenatal fractures, and the mode of delivery that would be safest for the fetus is not known. We conducted systematic analyses of the largest cohort of individuals with OI (n = 540) enrolled to date in the OI Linked Clinical Research Centers. Self-reported at-birth fracture rates were compared among individuals with OI types I, III, and IV. Multivariate analyses utilizing backward-elimination logistic regression model building were performed to assess the effect of multiple covariates, including method of delivery, on fracture-related outcomes. When accounting for other covariates, at-birth fracture rates did not differ based on whether delivery was by vaginal route or by cesarean delivery (CD). Increased birth weight conferred higher risk for fractures irrespective of the delivery method. In utero fracture, maternal history of OI, and breech presentation were strong predictors for choosing CD. Our study, the largest to analyze the effect of various factors on at-birth fracture rates in OI, shows that CD is not associated with decreased fracture rate. With the limitation that the fracture data were self-reported in this cohort, these results suggest that CD should be performed only for other maternal or fetal indications, not for the sole purpose of fracture prevention in OI.Genet Med 18 6, 570-576.


Diagnosis of common bacterial causes of urethritis in men by Gram stain, culture and multiplex PCR.
Urethritis is one of the most important causes of morbidity and mortality in developing countries. The aim of this study was to detect common bacterial causes of urethritis in men by Gram stain, culture and multiplex PCR.185 male patients who presented at the Skin and venereal clinic of the Dhaka Medical College, Bangladesh with clinical symptoms suggestive of urethritis were enrolled in this study. Urethral discharges were tested for detection of Neisseria gonorrhoeae by Gram stain, culture and PCR. Multiplex PCR assay was done to detect DNA of Chlamydia trachomatis, Ureaplasma urealyticum and Mycoplasma genitalium. Out of 185 participants, 30.27% and 14.6% were infected by Neisseria gonorrhoeae and Chlamydia trachomatis respectively. None of the individuals was found positive for either Ureaplasma urealyticum or Mycoplasma genitalium. Among the Neisseria gonorrhoeae positive patients 27.57% were positive from Gram stain, 26.49% were culture positive, 30.27% were positive by PCR (p<0.001). 32.65% of the Neisseria gonorrhoeae isolates were penicillinase producers and 83.67% were susceptible to ceftriaxone. Considering culture as the gold standard, the sensitivity and specificity of PCR for the detection of Neisseria gonorrhoeae was 100%, and 94.85% respectively with an accuracy of 96.22%. 3.73% of the 134 smear negative and 5.15% of the 136 culture negative samples were positive by PCR. PCR was the most sensitive and rapid method for the diagnosis of urethritis. Multiplex PCR may be a useful approach to laboratory diagnosis of urethritis in men for its high sensitivity and specificity.


Expanding services in a shrinking economy: desktop document delivery in a dental school library.
How can library staff develop and promote a document delivery service and then expand the service to a wide audience? The setting is the library at the Indiana University School of Dentistry (IUSD), Indianapolis. A faculty survey and a citation analysis were conducted to determine potential use of the service. Volume of interlibrary loan transactions and staff and equipment capacity were also studied. IUSD Library staff created a desktop delivery service (DDSXpress) for faculty and then expanded the service to practicing dental professionals and graduate students. The number of faculty using DDSXpress remains consistent. The number of practicing dental professionals using the service is low. Graduate students have been quick to adopt the service. Through careful analysis of capacity and need for the service, staff successfully expanded document delivery service without incurring additional costs. Use of DDSXpress is continually monitored, and opportunities to market the service to practicing dental professionals are being investigated.


Switching from a high-fat cellulose diet to a high-fat pectin diet reverses certain obesity-related morbidities.
Reducing caloric intake is a proven intervention for mitigating and modulating morbidities associated with overnutrition. Caloric restriction is difficult to affect clinically, therefore, dietary interventions that ameliorate the adverse consequences of overnutrition in the presence of a high-calorie diet would be of value. Mice were fed an obesogenic diet containing 60% fat + 10% cellulose (HFC), or a control diet containing 10% fat + 10% cellulose (LFC) for 12 wks. Subgroups of mice were then switched from HFC to each of the following diets for an additional 5 wks: 1) 60% fat + 10% pectin (HFP), 2) LFC or 3) 10% fat + 10% pectin (LFP). To test for statistical differences, one-way or two-way ANOVAs were used with or without repeated measurements as needed. In comparison to HFC, HFP prevented additional weight gain while LFC and LFP triggered weight loss of 22.2 and 25.4%, respectively. Mice continued on HFC experienced a weight increase of 26% during the same 5 wk. interval. After 12 wks, HFC decreased mouse locomotion by 18% when compared to control diet, but a diet switch to LFC or LFP restored mouse movement. Importantly, HFP, LFC, and LFP reduced fasting blood glucose when compared to HFC. Likewise, HFP, LFC and LFP improved glucose tolerance and decreased fatty liver by 37.9, 49.8, 53.6 and 20.2%, 37.2, 43.7%, respectively. Taken together, the results indicate that the dietary fiber pectin can mitigate some adverse consequences of overnutrition even in the presence of high-fat.


Content framing role on public sentiment formation for pre-crisis detection on sensitive issue via sentiment analysis and content analysis.
Social media has been tremendously used worldwide for a variety of purposes. Therefore, engagement activities such as comments have attracted many scholars due its ability to reveal many critical findings, such as the role of users' sentiment. However, there is a lacuna on how to detect crisis based on users' sentiment through comments, and for such, we explore framing theory in the study herein to determine users' sentiment in predicting crisis. Generic content framing theory consists of conflict, economic, human interest, morality, and responsibility attributes frame as independent variables whilst sentiment as dependent variables. Comments from selected Facebook posting case studies were extracted and analysed using sentiment analysis via Application Programme Interface (API) webtool. The comments were then further analysed using content analysis via Positive and Negative Affect Schedule (PANAS) scale and statistically evaluated using SEM-PLS. Model shows that 44.8% of emotion and reactions towards sensitive issue posting are influenced by independent variables. Only economic consequences and responsibility attributes frame had correlation towards emotion and reaction at p<0.05. News reporting on direction towards economic and responsibility attributes sparks negative sentiment, which proves that it can best be described as pre-crisis detection to assist the Royal Malaysian Police and other relevant stakeholders to prevent criminal activities in their respective social media.


Binding of dyes to hydroxyapatite treated with cetylpyridinium chloride or cetrimonium bromide.
The effect of cetylpyridinium chloride (CPC) and cetrimonium bromide (CTAB) on the adsorption of some acidic food dyes to hydroxyapatite was studied. The dyes investigated were brilliant blue (FD&C Blue No. 1), tartrazine (FD&C Yellow No. 5), sunset yellow (FD&C Yellow No. 6) and amaranth (FD&C Red No. 2). The apatite had adsorbed 9.2 mumol CPC per g dry weight. The adsorbed CPC was in equilibrium with a free concentration of 20 microgram/ml (58 micrometer). The adsorption of CPC and CTAB to the apatite was followed by an increased ability of the crystals to bind the dyes. The dyes were very firmly adsorbed and were not released during a series of washings. Untreated apatite showed only a minor affinity for the dyes. The adsorbed dyes were easily washed out. CPC and CTAB showed the smae specific ability to increase the binding capacity of the apatite. The results are discussed and related to the formation of stains on the teeth in persons using quaternary ammonium compounds for mouthrinsing. A mechanism explaining the production of stains is proposed.


Qualification of a high-efficiency, gated spectrometer for x-ray Thomson scattering on the National Ignition Facility.
We have designed, built, and successfully fielded a highly efficient and gated Bragg crystal spectrometer for x-ray Thomson scattering measurements on the National Ignition Facility (NIF). It utilizes a cylindrically curved Highly Oriented Pyrolytic Graphite crystal. Its spectral range of 7.4-10 keV is optimized for scattering experiments using a Zn He-α x-ray probe at 9.0 keV or Mo K-shell line emission around 18 keV in second diffraction order. The spectrometer has been designed as a diagnostic instrument manipulator-based instrument for the NIF target chamber at the Lawrence Livermore National Laboratory, USA. Here, we report on details of the spectrometer snout, its novel debris shield configuration and an in situ spectral calibration experiment with a Brass foil target, which demonstrated a spectral resolution of E/ΔE = 220 at 9.8 keV.


Update on thoracic paravertebral blocks.
Thoracic paravertebral block was widely practised at the beginning of the 20th century. It has enjoyed a renaissance in the past decade. This form of afferent blockade is the technique of injecting local anaesthetic into the thoracic paravertebral space. Thoracic paravertebral analgesia is mostly indicated for unilateral surgical procedures of the thorax and abdomen. Compared to the other available regional techniques such as epidural, intercostal and interpleural, paravertebral blocks offer comparable or better analgesia with less side effects. Thoracic paravertebral blocks deserve greater consideration and investigation.


Volume fluctuations and compressibility of a vibrated granular gas.
The volume fluctuations in the steady state reached by a vibrated granular gas of hard particles confined by a movable piston on the top are investigated by means of event-driven simulations. Also, a compressibility factor, measuring the response in volume of the system to a change in the mass of the piston, is introduced and measured. From the second moment of the volume fluctuations and the compressibility factor, an effective temperature is defined by using the same relation as obeyed by equilibrium molecular systems. The interpretation of this effective temperature and its relationship with the granular temperature of the gas, and also with the velocity fluctuations of the movable piston, is discussed. It is found that the ratio of the temperature based on the volume fluctuations to the temperature based on the piston kinetic energy obeys simple dependencies on the inelasticity and on the piston-particle mass ratio.


Homotopy analysis method to study a quadrupole mass filter.
The homotopy analysis method (HAM) is applied to study the behavior of a hyperbolic rods of quadrupole mass filter and a sinusoidal potential form V(ac) cos(Ωt). Numerical computation method of a 20th-order HAM is employed to compare the physical properties of the confined ions with fifth-order Runge-Kutta method. Also, comparison is made for the first stability region, the ion trajectories in real time, the polar plots, and the ion trajectory in x - y plan. The results show that the two methods are fairly similar; therefore, the HAM method has potential application to solve linear and nonlinear equations of the charge particle confinement in quadrupole field.


Enhancement of an electroporation system for gene delivery using electrophoresis with a planar electrode.
In this paper a new electroporation (EP) system is developed, which includes an EP microchip and a logic circuit, which combined with electrophoresis (ES), can provide site-specific enhancement of gene concentration. In this ES-EP microchip, an arc planar electrode provides the ES function for DNA attraction, and interdigitated array electrodes provide appropriate electric fields for the EP on the chip surface. In addition, the adherent cells can be manipulated in situ without detachment of the ES-EP microchip, which performs the "Lab on a chip". Experimental results have shown that the efficiency of gene transfection with an attracting-electric field (35.89%) becomes much higher than that without an attracting-electric field (16.62%). Cell numbers as low as 10(4) cells, and DNA as little as 4 microg are sufficient for evaluating the phenotypic effects following the over-expression of the introduced genes on the ES-EP microchip. The proposed system has the advantages of portability, cost-effectiveness, a high transfection rate and ease of operation.


Dual Imprinted Polymer Thin Films via Pattern Directed Self-Organization.
Synthetic topographically patterned films and coatings are typically contoured on one side, yet many of nature's surfaces have distinct textures on different surfaces of the same object. Common examples are the top and bottom sides of the butterfly wing or lotus leaf, onion shells, and the inside versus outside of the stem of a flower. Inspired by nature, we create dual (top and bottom) channel patterned polymer films. To this end, we first develop a novel fabrication method to create ceramic line channel relief structures by converting the oligomeric residue of stamped poly(dimethylsiloxane) (PDMS) nanopatterns on silicon substrates to glass (SiOx, silica) by ultraviolet-ozone (UVO) exposure. These silica patterned substrates are flow coated with polystyrene (PS) films and confined within an identically patterned top confining soft PDMS elastomer film. Annealing of the sandwich structures drives the PS to rapidly mold fill the top PDMS pattern in conjunction with a dewetting tendency of the PS on the silica pattern. Varying the film thickness h, from less than to greater than the pattern height, and varying the relative angle between the top-down and bottom-up patterned confinement surfaces create interesting uniform and nonuniform digitized defects in PS channel patterns, as also a defect-free channel regime. Our dual patterned polymer channels provide a novel fabrication route to topographically imprinted Moiré patterns (whose applications range from security encrypting holograms to sensitive strain gauges), and their basic laser light diffractions properties are illustrated and compared to graphical simulations and 2D-FFT of real-space AFM channel patterns. While traditional "geometrical" and "fringe" Moiré patterns function by superposition of two misaligned optical patterned transmittance gratings, our topographic pattern gratings are quite distinct and may allow for more unique holographic optical characteristics with further development.


Experiences and Perpetration of Recent Intimate Partner Violence Among Women and Men Living in an Informal Settlement in Nairobi, Kenya: A Secondary Data Analysis.
Evidence suggests an overlap between intimate partner violence (IPV) experience and perpetration. However, few studies in sub-Saharan Africa have investigated experience and perpetration of IPV among women and men within the same community. This study reports prevalence of past-year IPV experience and perpetration among women and men living in an informal settlement in Nairobi, Kenya, and factors associated with IPV. Data analyzed for this study involved a geographically distributed random sample of 273 women and 429 men who participated in a community survey. We approximated prevalence of IPV experience and perpetration and used logistic regression for estimating associations between individual-level factors and IPV. Women and men experienced similar levels of IPV, but a significantly higher proportion of men reported physical and sexual IPV perpetration. Witnessing violence between parents in childhood was associated with women's physical and sexual, and men's sexual IPV experience; and with women perpetrating emotional, and men perpetrating sexual IPV. Less equitable gender attitudes were associated with men's perpetration of physical IPV. More equitable gender knowledge was associated with women's experience of sexual IPV, and with men perpetrating IPV. Perceived skills to challenge gender inequitable practices were negatively associated with men perpetrating sexual IPV. In conclusion, we found IPV experience and perpetration were highly correlated, and that, contrary to commonly reported gender gaps, men and women experienced similar rates of IPV. We make suggestions for future research, including on IPV prevention interventions in areas with such IPV prevalence that would be beneficial for women and men and future generations.


Cell based cancer vaccines: regulatory and commercial development.
There is both clinical and regulatory drive to expedite development of safe, efficacious cancer therapies. Stimulation of the patients immune system through vaccination with tumour cells has long been at the vanguard of cancer therapeutic vaccines, and several have been demonstrated to be safe and to have efficacy in early clinical trials for a range of cancers including melanoma, renal cell carcinoma, prostate and colorectal cancers. A number of development-stage vaccines and strategies are currently being tested, utilising either autologous or allogeneic tumour cells, which may also have been ex vivo manipulated (e.g. cytokine transfected cells). It seems likely that clinical trial success, and hence patient benefit, could be improved through better patient identification, possibly by the discovery and use of novel immune response biomarkers. In this review, we aim to summarise the state of tumour cell vaccines in commercial development and to explore not only the difficulties of determining efficacy, but also the production challenges faced when developing a vaccine from proof of principle to pivotal phase III trials.


Patient perception and acceptability of multidose dry powder inhalers: a randomized crossover comparison of Diskus/Accuhaler with Turbuhaler.
This study was designed to provide information on correct use and preference to features and device handling of two multidose dry powder inhalers, the Diskus/Accuhaler and the Turbuhaler. A total of 169 powder-naive patients (mean age 40 years) with asthma or chronic obstructive pulmonary disease (COPD) were enrolled in a randomized crossover comparison of both inhalers. An effective use of either inhaler was assessed before (leaflet only) and after inhaler education. Ease of use especially during an attack and the presence of a dose counter were regarded as the most important features for an ideal inhaler. The percentage of correct handling maneuvers and the percentage of patients achieving 100% of correct maneuvers increased significantly (p < 0.001) after inhaler education in both devices, but percentage of correct use after the intervention was significantly higher for the Diskus/Accuhaler (92.6%) than for the Turbuhaler (89.8%; p = 0.036). Overall 60% of patients thought the Diskus/Accuhaler was preferable to the Turbuhaler (p < 0.001). The main reasons given were presence of a dose counter, perceived ease of use including ease of learning to use, design, and attached cover. Among those who preferred the Turbuhaler device, the main reason cited was small size, discreetness, and ease of holding. In the multivariate analysis, inhaler education (p = 0.005) and education level (p = 0.009) were significantly associated with the percentage of correct maneuvers. Age, sex, or tested inhaler showed no effect on appropriateness of the inhalation technique.


Bronchial colonization and postoperative respiratory infections in patients undergoing lung cancer surgery.
To evaluate the risk factors associated with postoperative respiratory infection in patients undergoing lung cancer surgery, with special emphasis on the perioperative pattern of airway colonization. Prospective cohort study. Department of Pneumology and Thoracic Surgery of a tertiary hospital. Seventy-eight consecutive patients undergoing lung cancer surgery were evaluated. Patients were followed up until hospital discharge or death. Fiberoptic bronchoscopies with bilateral protected specimen brush or bronchial aspirates were performed during anesthesia prior to the initiation of the surgical procedure. Sixty-five patients (83%) had perioperative bronchial colonization by either potentially pathogenic microorganisms (PPMs) [28 patients, 36%] or non-potentially pathogenic microorganisms (56 patients, 72%). The 24 patients (31%) with a postoperative respiratory infection (pneumonia, purulent tracheobronchitis, or pleural empyema) had significantly higher perioperative bronchial colonization by PPMs (15 patients [63%] vs 13 patients [24%], p = 0.003) and a higher bacterial index (mean +/- SD, 3.6 +/- 3.3 vs 0.9 +/- 1.4; p = 0.003), compared to patients without infection. The agreement between pathogens found in perioperative evaluation and during postoperative infection was total in 5 patients (21%), partial in 5 patients (21%), and no concordance in 14 patients (58%). In the multivariate analysis, the presence of perioperative airway colonization by a PPM (odds ratio [OR], 6.9; p = 0.001) and a higher postoperative pain score (OR, 4.1; p = 0.014) were independent predictors of postoperative respiratory infection. Adequate control of postoperative pain, as well as the conditions that potentially cause airway colonization by PPMs, could be beneficial in preventing postoperative respiratory infections after lung cancer surgery.


Beyond equivalence of care in prison pharmacy.
Prison healthcare has undergone a significant transformation over recent times. The main aim of these changes was to ensure prisoners received the same level of care as patients in the community. Prisons are a unique environment to provide healthcare within. Both the environment and the patient group provide a challenge to healthcare delivery. One of the biggest challenges currently being faced by healthcare providers is the misuse and abuse of prescription medication. It seems that the changes that have been made in prison healthcare, to ensure that prisoners receive the same level of care as patients in the community over recent times, have led to an increase in this problem. Prison pharmacy is ideally placed to help reduce the misuse and abuse of prescription medication. This can be achieved by using the skills and knowledge of the pharmacy department to ensure appropriate prescribing of medication liable to misuse and abuse.


Influence of very small bubbles on kLa measurement in viscous microbiological cultures.
In gas-liquid dispersions based on viscous non-Newtonian fluids, numerous very small bubbles are formed due to their high residence times in contacting devices such as bubble columns. The influence of these small bubbles on the measurement of the volumetric mass transfer coefficient in the contactor by the dynamic CO(2) gas analysis method is discussed. It is found that their effect on this measuring technique is insignificant compared to that when using the conventional dissolved-oxygen technique.


Review of research related to Parse's Theory of Human Becoming.
Ninety-three retrievable studies guided by the human becoming theory between 1985 and 2006, are reviewed. A summary of the studies is tabulated according to the two basic human becoming research methods, the human becoming applied research method, and other qualitative research methods using human becoming as the frame of reference. The authors provide an overview of the studies and the human becoming research methods and further illuminate the findings of studies reviewed under four major themes that describe the phenomena studied.


Decreased cholinesterase level combined with renal dysfunction and sympathetic denervation associated with increased cardiac mortality in systolic heart failure.
Cardiac mortality in patients with heart failure (HF) is likely to be aggravated by malnutrition, assessed by serum cholinesterase (ChE) level, as well as by kidney dysfunction or impairment of cardiac sympathetic denervation. Their prognostic interactions, however, have not been determined. A total of 991 systolic HF patients were enrolled in our HF database following clinical evaluation including evaluation of the nutrition state and assessment of standardized heart-to-mediastinum ratio (sHMR) of iodine-123-labeled meta-iodobenzylguanidine activity. Patients were followed up for an average of 43 months with the primary endpoint of fatal cardiac events (CEs). The CE patient group had a lower level of ChE, lower estimated glomerular filtration rate (eGFR) and lower late sHMR than those in the non-CE patient group. A five-parameter model with the addition of serum ChE selected in the multivariate logistic analysis (model 2) significantly increased the AUC predicting risk of cardiac events compared with a four-parameter model without serum ChE (model 1), and net reclassification analysis also suggested that the model with the addition of serum cholinesterase significantly improved cardiac event prediction. Moreover, in overall multivariate Cox hazard analysis, serum ChE, eGFR and late sHMR were identified to be significant prognostic determinants. HF patients with two or all of the prognostic variables of serum ChE < 230 U/L, eGFR < 48.8 ml/min/1.73 m2 and late sHMR < 1.90 had significantly and incrementally increased CE rates compared to those in HF patients with none or only one of the prognostic variables. Decreases in cholinesterase level and kidney function further increase cardiac mortality risk in HF patients with impairment of cardiac sympathetic innervation.


Treatment of peyronie's disease with combination of clostridium histolyticum collagenase and penile traction therapy: a prospective, multicenter, single-arm study.
The aim of this paper is to analyze our experience with intraplaque administration of collagenase from Clostridium Histolyticum (CCH) together with penile modeling for selected patients with Peyronie's disease (PD). We conducted a prospective, multicenter, single-arm study. Patients were included from October 2015 to August 2019. We carried out the I + E PROTOCOL (IMPRESS + extender). Each cycle involved administration of two injections of CCH separated 24-72 h, up to a maximum of four cycles. 24-48 h after injection patients underwent penile modeling maneuvers with the use of a PTD at home for at least 4 h a day. After each cycle, penile curvature was evaluated by the Kelami test. Mean pretreatment curvature was 57° (30-100). Eighty-seven patients underwent at least a single cycle and were eligible for analysis. Mean number of cycles administered was 2. Final average curvature after treatment, regardless of the number of cycles was 34°, with a mean reduction in curvature of -23.29° (-41%). Across the first three cycles we found statistically significant differences in the means in terms of the degrees of curvature after each cycle (p < 0.05), however this was not maintained in the fourth cycle. Statistical significance was also found when comparing the initial and final curvature after the complete treatment. We can conclude that treatment with CCH for PD is safe and effective. The concomitant use of CCH and PTT may limit the number of treatment cycles necessary to optimize outcomes when compared with CCH alone.


A comparison of results of carotid endarterectomy in octogenarians and nonagenarians to younger patients from the Mid-America Vascular Study Group and the Society for Vascular Surgery Vascular Quality Initiative.
Carotid endarterectomy (CEA) reduces stroke risk in selected patients. However, CEA risk profile may be different in older patients. We compared characteristics and outcomes of octogenarians and nonagenarians with those of younger patients. Deidentified data from CEA patients were obtained from the Society for Vascular Surgery Vascular Quality Initiative (VQI) database. Prior CEA, carotid artery stent, or combined CEA and coronary artery bypass were excluded, yielding 7390 CEAs in octogenarians and nonagenarians (≥80 years of age) and 35,303 CEAs in younger patients (<80 years of age). We compared post-CEA outcomes, including periprocedural cerebral ischemic events and death, and details such as operative time, bleeding, and return to surgery. Octogenarians and nonagenarians were more likely to have pre-CEA neurologic symptoms (51.4% vs 45.6%; P < .001) and to have never smoked (37.8% vs 22.0%; P < .001), and they were slightly more likely to have required urgent CEA (16.1% vs 13.4%; P < .001). Stenosis ≥70% was similar (octogenarians and nonagenarians, 94.2%; younger patients, 94.4%; P = .45). Perioperative ipsilateral neurologic events and ipsilateral stroke were slightly more common among octogenarians and nonagenarians (1.6% vs 1.1% [P < .001] and 1.2% vs 0.8% [P = .002]). Multivariate modeling (logistic regression) showed that pre-CEA neurologic symptoms (odds ratios, 1.35 [P = .005] and 1.42 [P = .007]), pre-CEA ipsilateral cortical ischemic event (odds ratios, 1.18 [P < .001] and 1.20 [P < .001]), and urgency (odds ratios, 1.75 [P < .001] and 1.67 [P < .001]) remained strong predictors of any ipsilateral neurologic event and any ipsilateral stroke, respectively. However, age ≥80 years remained a significant predictor of these outcomes (odds ratios, 1.37 [P = .003] and 1.44 [P = .004]). Kaplan-Meier estimated survival was lower for octogenarians and nonagenarians at 30 days and 1 year (98.6% vs 99.4% and 93.7% vs 97.0%; log-rank, P < .001). Age ≥80 years was also associated with a greater rate of discharge to other than home after CEA, a difference that was only partially explained by comorbidities in multivariate modeling. CEA was performed with low rates of perioperative neurologic events and mortality. Multivariate testing showed that the higher rate of neurologic complications in octogenarians and nonagenarians appeared partially related to symptomatic status and urgent surgery; but after adjusting for these factors, age ≥80 years still predicted a slightly higher rate. Periprocedural CEA outcomes appear similar in comparing older and younger patients, although longer term survival is lower for older patients, and older patients are at greater risk of discharge to other than home. CEA was associated with slightly higher risk of neurologic complications in older patients but may be considered appropriate for selected octogenarians and nonagenarians.


Energy level alignment at the anode of poly(3-hexylthiophene)/fullerene-based solar cells.
We have used ultraviolet photoelectron spectroscopy to investigate the energy-level and band alignment near the anode for poly(3-hexylthiophene)/[6,6]-phenyl-C(61)-butyric acid methyl ester (P3HT/PCBM)-based organic solar cells. Analysis of various batches of indium-tin oxide (ITO) revealed that the photoresist residues had a strong effect, reducing the work functions of ITO (Phi(ITO)) by as much as 0.61 eV. The energy-level alignment of poly(3,4-ethylenedioxythiophene)/ITO (Phi(PEDOT/ITO)) interfaces obey the Mott-Schottky rule at values of Phi(ITO) of less than 3.92 eV. In contrast, we observed Fermi-level pinning for the blend/PEDOT interfaces at values of Phi(PEDOT/ITO) greater than 4.26 eV; this finding is consistent with a previous report that the positive polaronic energy of P3HT is equal to 4.0 eV. Consequently, we suspect that the similar efficiency levels and open-circuit voltages of devices prepared from various ITO samples were due mainly to the constant interfacial energy barrier at the blend/PEDOT interface with Fermi-level pinning.


Acceptability and disintegration rates of orally disintegrating risperidone tablets in patients with schizophrenia or schizoaffective disorder.
To investigate the disintegration profile, acceptability, and tolerability of orally disintegrating risperidone tablets in patients with schizophrenia or schizoaffective disorder. Ten patients stable for at least 10 days on monotherapy with oral risperidone 2 mg to 4 mg taken once daily were switched for 7 days to an equivalent dosage of orally disintegrating risperidone. Visual assessments for time to initial and complete disintegration were collected at each visit. Clinical Global Impression of Severity scores were collected at baseline and at the last visit. Patient acceptance of the new formulation, rated according to a visual analog scale, was obtained at the last visit. All patients maintained stable clinical status. Mean time to initial disintegration was 5.1 seconds, SD 0.8, and mean time to complete disintegration was 29.4 seconds, SD 18.4. The formulation was rated as very acceptable. Adverse events were reported by 5 patients; all were mild. The orally disintegrating risperidone tablets were well tolerated and rated as very acceptable by all patients.


[Early fluid resuscitation in severe acute pancreatitis].
Fluid resuscitation is the cornerstone in the early treatment of severe acute pancreatitis(SAP). The endpoints of fluid therapy should be closely monitored early in the disease course by different methods, such as clinical status, pressure indicators, volume indicators, the maintain of microcirculation and the tissue oxygenation. To avoid volume overload that may lead to complications such as pulmonary edema and abdominal hypertension, it is critical to adjust the ratio of crystalloid-colloid and the speed of the liquid timely according to the dynamically assessment of fluid responsiveness and tolerance, the perfusion of macrocirculation and microcirculation and the stage of the fluid resuscitation, so as to improve the efficacy and safety of early fluid resuscitation in the treatment of SAP.


Heterogeneity, polydispersity, and physiologic role of corneal proteoglycans.
Gel chromatography, affinity chromatography, ultracentrifugation, enzymic fragmentation, and analysis of amino acids, hexosamines and neutral sugars were used to characterize a heterogeneous fraction of proteoglycans from bovine corneal stroma. The results indicate that the fraction largely consists of a mixture of the 2 main types of corneal proteoglycans described earlier, namely keratan sulfate proteoglycans and chondroitin sulfate-rich proteoglycans with covalently bound oligosaccharides. Models for the structure of proteoglycans are suggested, an it is concluded that the molecular size of corneal proteoglycans makes them appropriate as 'spacers' between the collagen fibrils, a property important for corneal transparency. Cornea is softer than cartilage because corneal proteoglycans are less underhydrated than cartilage proteoglycans.


Dealloying of Cu-Based Metallic Glasses in Acidic Solutions: Products and Energy Storage Applications.
Dealloying, a famous ancient etching technique, was used to produce nanoporous metals decades ago. With the development of dealloying techniques and theories, various interesting dealloying products including nanoporous metals/alloys, metal oxides and composites, which exhibit excellent catalytic, optical and sensing performance, have been developed in recent years. As a result, the research on dealloying products is of great importance for developing new materials with superior physical and chemical properties. In this paper, typical dealloying products from Cu-based metallic glasses after dealloying in hydrofluoric acid and hydrochloric acid solutions are summarized. Several potential application fields of these dealloying products are discussed. A promising application of nanoporous Cu (NPC) and NPC-contained composites related to the energy storage field is introduced. It is expected that more promising dealloying products could be developed for practical energy storage applications.


[Mixed ductal and acinar cell cancer of the pancreas head; report of a case].
A 63 year old Japanese man was admitted in Feb. 1983, with his chief complaint of upper abdominal pain. Physical examination showed only resistance in the right hypochondrium on palpation, but no icteric conjunctiva and skin. A large global tumor of the pancreas head was visualised as a hyperechoic mass with irregularly shaped cystic cavity in ultrasonography, as a hypervascular mass with lucent area in celiac arteriography, and as a mass lesion with low density area in body computerized tomography. Cancer cells were histologically confirmed on specimens taken by fine needle aspiration biopsy under ultrasonic guidance. Cancer of 6.5 X 6.0 X 4.0 cm in size was resected by pancreaticoduodenectomy. Four months after operation, two liver metastatic nodules were resected by right hepatic lobectomy. Histologically, tumor was composed of two characteristic patterns, acinar cell cancer and duct cell cancer, which were confirmed by immunohistochemical techniques. The patient is doing well 3 years and 3 months postoperatively without evidence of recurrent cancer. To our best knowledge, this case is the seventh of mixed ductal and acinar cancer in the world, but the previous 6 cases were reported on autopsy specimens.


Association between risk of acquiring HIV and beliefs and perceptions about the lived experience of HIV/AIDS among HIV-negative or untested men who have sex with men.
The study aim was to assess whether the sexual behaviour of HIV-negative or untested men who have sex with men (MSM) was related to their perceptions of what it is like to live with HIV/AIDS, their beliefs or their attitudes to highly active antiretroviral treatments. Any unprotected anal intercourse (UAI) with casual partners was used as the sexual-risk indicator. The study enrolled 261 MSM. There were no significant differences between beliefs, attitudes and perceptions about HIV/AIDS, knowledge of post-exposure prophylaxis (PEP) or exposure to the HIV/AIDS epidemic among those who had had UAI with casual partners and those that had not (P>0.12). Those who considered that low levels of viral load and withdrawing before ejaculation reduced the risk of HIV transmission were significantly more likely to have had UAI with a casual partner (P=0.03). Only a minority of MSM engaging in UAI were optimistic about antiretroviral therapy. The study participants were in general pessimistic about life with HIV/AIDS despite their risk-taking sexual behaviour.


Ion distribution in electrified micropores and its role in the anomalous enhancement of capacitance.
The distribution of K+ ions in electrified slit-shaped micropores with pore widths ranging from 9.36 to 14.7 A was studied using molecular dynamics simulations. We show that, in slit pores with pore widths between 10 and 14.7 A, the K+ ion distribution differs qualitatively from that described by classical electrical double-layer (EDL) theories in that fully hydrated K+ ions accumulate primarily in the central plane of the slit pores. This phenomenon disappears when the pore width is narrower than 10 A. Ion hydration and water-water interactions, which are rarely considered in prior EDL theories for micropores, are found to be responsible for this behavior. On the basis of these results, we have developed a new sandwich capacitance model to describe the capacitance of the EDLs formed by K+ ions enclosed in slit-shaped micropores. This model is capable of predicting the anomalous enhancement of capacitance experimentally observed in micropores.